A Research Guide for
Alzheimer's / ADRD

Alzheimer’s destroys the neurons that produce acetylcholine, a neurotransmitter critical for memory and attention. Cholinesterase inhibitors work by blocking the enzyme that breaks down acetylcholine — increasing the amount available at synapses. They do not replace lost neurons; they help the remaining ones work more efficiently.

Donepezil (Aricept® and generics)

The workhorse of Alzheimer’s treatment. Approved for all stages — mild, moderate, and severe — making it the only cholinesterase inhibitor with a severe-stage indication.

• Dosing: Start at 5 mg once daily at bedtime for 4–6 weeks. Titrate to 10 mg once daily. A higher-dose 23 mg once-daily tablet is available for moderate-to-severe Alzheimer’s (MMSE 0–20) for patients already on 10 mg for ≥3 months; FDA approved 2010. The clinical benefit of 23 mg over 10 mg is modest and comes with more GI side effects — some specialists reserve it for patients who seem to plateau on 10 mg.
• Why at bedtime? The cholinergic side effects (nausea, vivid/disturbing dreams) are better tolerated when the patient is asleep through the peak. If vivid dreams become intolerable, some clinicians switch to morning dosing.
• Common side effects: Nausea, diarrhea, vomiting, muscle cramps, insomnia, vivid dreams, anorexia. Usually dose-dependent and most pronounced at the start and with titration.
• Cardiac monitoring: Donepezil slows the heart rate (vagotonic effect). It can worsen sick sinus syndrome or heart block. Baseline ECG is reasonable in anyone with known conduction issues or on other rate-slowing drugs (beta-blockers, diltiazem). Syncope and falls due to bradycardia have been reported; inform patients and families.
• Drug interactions: Avoid combining with other anticholinergic medications (they work at cross purposes — see the list to avoid below). Beta-blockers and diltiazem can potentiate bradycardia. NSAIDs slightly increase GI bleed risk (cholinergic GI effects + NSAID gastropathy).
• Discontinuation: If stopping, taper rather than abrupt cessation to avoid a rebound worsening of cognition or behavior.

Rivastigmine (Exelon® and generics)

Approved for mild-to-moderate Alzheimer’s and Parkinson’s disease dementia — the only cholinesterase inhibitor approved for the latter, which makes it the preferred choice when there is Lewy body or parkinsonian pathology in the differential.

• Oral dosing: Start at 1.5 mg twice daily with food. Increase by 1.5 mg twice daily every 2 weeks as tolerated. Target: 6 mg twice daily (3–6 mg twice daily is the approved range). Taking with food significantly reduces nausea.
• Transdermal patch (Exelon Patch): 4.6 mg/24h starting dose; titrate to 9.5 mg/24h after 4 weeks; 13.3 mg/24h patch available for patients who plateau. The patch has significantly lower rates of GI side effects than oral rivastigmine — it is the preferred form for patients with GI intolerance or who cannot reliably take pills. Apply to the upper back, upper arm, or chest; rotate sites; remove the old patch before applying the new one.
• Side effects: Same cholinergic profile as donepezil but GI effects more prominent with oral form. Skin irritation at the patch site in 10–15%; use rotation and mild topical steroid if needed.
• Practical note: Patients who experience unacceptable GI side effects on donepezil should be offered the rivastigmine patch before abandoning the drug class entirely.

Galantamine (Razadyne® ER and generics)

Approved for mild-to-moderate Alzheimer’s. Has a dual mechanism: cholinesterase inhibition plus allosteric modulation of nicotinic acetylcholine receptors (which may amplify the effect of remaining acetylcholine).

• Dosing (ER formulation, once daily): Start at 8 mg once daily for 4 weeks; increase to 16 mg once daily for 4 weeks; target 24 mg once daily. Take with morning meal to reduce nausea.
• Side effects: Similar GI profile to donepezil; bradycardia risk similar.
• Note: The immediate-release form requires twice-daily dosing; most clinicians now use ER exclusively for better adherence.

Practical point on cholinesterase inhibitors: There is no clear evidence that one is superior to another for efficacy in Alzheimer’s. The choice is driven by tolerability, route preference, comorbidities (Lewy body or Parkinson’s features favor rivastigmine; bradycardia concerns may favor galantamine which has slightly less cardiac effect in some series), and cost. Generic versions of all three are widely available and affordable. If a patient cannot tolerate one, trying another is reasonable.

Memantine works differently from cholinesterase inhibitors. It blocks NMDA (N-methyl-D-aspartate) glutamate receptors, which play a role in excitotoxicity — the neuronal damage caused by excessive glutamate signaling that contributes to cognitive decline in moderate-to-severe Alzheimer’s. It does not boost acetylcholine; it protects neurons from a different mechanism of injury.

• Indication: FDA-approved for moderate-to-severe Alzheimer’s (MMSE 3–14 in pivotal trials). Often started when a patient transitions from mild to moderate dementia.
• Immediate-release (Namenda) dosing: Start at 5 mg once daily for 1 week; increase to 5 mg twice daily for 1 week; increase to 10 mg in the morning and 5 mg in the evening for 1 week; target 10 mg twice daily.
• Extended-release (Namenda XR) dosing: Start at 7 mg once daily; increase by 7 mg weekly to target 28 mg once daily. Once-daily dosing improves adherence.
• Side effects: Generally well tolerated. Dizziness, headache, constipation, and confusion at initiation. Does not cause the GI side effects of cholinesterase inhibitors. Can cause agitation in some patients — watch carefully at initiation.
• Drug interactions: Amantadine (a Parkinson’s drug) uses the same NMDA receptor mechanism — combination is not recommended. Alkalinizing the urine (sodium bicarbonate, carbonic anhydrase inhibitors like acetazolamide) reduces memantine clearance — may increase toxicity.

Namzaric® (memantine ER + donepezil combination)

A fixed-dose combination capsule containing donepezil 10 mg + memantine ER 28 mg once daily. Approved for moderate-to-severe Alzheimer’s in patients already stabilized on both agents separately. The primary benefit is pill consolidation. It is available as branded and generic.

When to start memantine: When the person transitions into the moderate stage (roughly CDR 2, MMSE 10–19). It is typically added to an existing cholinesterase inhibitor rather than used alone. Combination therapy (donepezil + memantine) has demonstrated additive benefit in multiple trials and is the standard of care for moderate-to-severe AD.

Behavioral and psychological symptoms of dementia (BPSD) affect up to 90% of people with Alzheimer’s at some point in the course and are the leading driver of caregiver burden and nursing-home placement. They include agitation, aggression, psychosis (delusions, hallucinations), depression, anxiety, apathy, sleep disruption, and wandering.

The cardinal rule: non-pharmacological approaches first, always. Look for underlying causes before reaching for medications (see non-pharmacological section below). Unmet needs, pain, constipation, urinary tract infections, environmental overstimulation, boredom, and dehydration are classic precipitants of sudden behavioral worsening. Treat these first.

Brexpiprazole (Rexulti®) — for Agitation in Alzheimer’s Dementia

FDA-approved May 2023 specifically for agitation associated with dementia due to Alzheimer’s disease — the first drug ever approved for this specific indication. This was a landmark regulatory event: prior to this, all medications used for agitation in dementia were off-label.

• Mechanism: An atypical antipsychotic (partial agonist at D2/D3 and 5-HT1A receptors; antagonist at 5-HT2A and histamine H1).
• Dosing: Start at 0.5 mg once daily for 7 days; increase to 1 mg once daily for 7 days; target 2 mg once daily. Dose can be increased to 3 mg once daily based on clinical response. Take at the same time each day, with or without food.
• Black box warning (antipsychotics in dementia): All antipsychotics carry an FDA black-box warning: elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death (1.6–1.7x mortality vs. placebo, primarily from cardiovascular events and infections). Before prescribing, document that non-pharmacological approaches were tried and failed, and obtain informed consent. Discuss the risk with the patient (if capable) and family.
• Other precautions: Metabolic syndrome (weight gain, glucose dysregulation), EPS (extrapyramidal symptoms), tardive dyskinesia with long-term use, orthostatic hypotension, QT prolongation. Monitor weight, fasting glucose, and lipids at baseline and periodically.
• Evidence base: The pivotal Phase 3 trial (Lee D et al., JAMA Neurology 2023; PMID 37930669) demonstrated a statistically significant reduction in the Cohen-Mansfield Agitation Inventory (CMAI) scores at 12 weeks. Effect size was modest but clinically meaningful for severe agitation.
• Insurance/prior auth: Because it is the first specifically approved agent for this indication, coverage varies. Some plans require documentation of failed trials of safer alternatives (antidepressants, non-pharmacological approaches) first.

Auvelity (dextromethorphan–bupropion ER) — for Agitation (Non-Antipsychotic)

FDA-approved in April 2026 for agitation associated with dementia due to Alzheimer’s disease — the first non-antipsychotic approved for this indication. Because it is not an antipsychotic, it avoids the antipsychotic black-box mortality warning, making it an important new option when agitation needs medication.

• What it is: A combination of dextromethorphan (an NMDA-receptor antagonist / sigma-1 agonist) and bupropion (which raises and stabilizes dextromethorphan blood levels). The same combination is also approved for major depression.
• Evidence base: Approved on the basis of the ADVANCE-1 (NCT03226522) and ACCORD-2 (NCT04947553) trials in Alzheimer’s agitation.
• Cautions: Can raise blood pressure and may lower the seizure threshold; it interacts with many medications (it inhibits CYP2D6). It must not be combined with MAOI antidepressants, and is avoided in people with a seizure disorder or a history of an eating disorder. Review your full medication list with your doctor.
• How it compares: Brexpiprazole (above) is an antipsychotic carrying a black-box mortality warning; Auvelity is the non-antipsychotic alternative. Your clinician will weigh both against non-drug approaches, which remain first-line.

Antidepressants for BPSD

Depression affects 40–50% of people with Alzheimer’s and is both underdiagnosed and undertreated. Antidepressants are also used for anxiety and, in some cases, agitation (as a safer alternative to antipsychotics).

• Escitalopram (Lexapro): Used off-label for agitation in Alzheimer’s as a generally safer alternative to antipsychotics, and often preferred over citalopram as its active enantiomer with a more favorable QT profile. (Note: the landmark CitAD trial actually tested citalopram, not escitalopram — Porsteinsson et al., JAMA 2014;311:682–691, PMID 24549548 — and is summarized under Citalopram below; an escitalopram-specific trial, S-CitAD, has been conducted separately.) Usual dose: 5–10 mg once daily (start low in elderly; renally dose-adjust if needed). Generally well tolerated; monitor for QT prolongation at higher doses, and note drug interaction with other QT-prolonging agents.
• Sertraline (Zoloft): SSRI; off-label use for depression, anxiety, and agitation in dementia. HTA-DD trial (PMID 22764089) showed no benefit over placebo for depression in AD specifically, but clinical experience remains positive for BPSD in general. Well tolerated.
• Citalopram: Previously used widely for agitation; fell out of favor after the CitAD/ADMET trial showed dose-dependent QT prolongation (FDA limits dose to 20 mg in those >60 or on interacting drugs). Escitalopram (the active enantiomer) is now preferred.
• Mirtazapine: An option when sleep disturbance, weight loss, and depression co-occur. Sedating at low doses (15 mg); antihistaminergic and appetite-stimulating. Can worsen morning grogginess.
• Venlafaxine, duloxetine: SNRI options for comorbid pain and depression.
• Tricyclic antidepressants (amitriptyline, nortriptyline): Generally AVOID — strong anticholinergic effects worsen cognition (see below).

Suvorexant (Belsomra®) — for Insomnia

FDA-approved in 2014 for insomnia and studied specifically in Alzheimer’s dementia. A dual orexin receptor antagonist (DORA) — it blocks the wake-promoting orexin signal rather than sedating the brain globally.

• Why it matters in dementia: Circadian disruption and insomnia are near-universal in moderate-to-severe Alzheimer’s. Traditional sleep aids (benzodiazepines, diphenhydramine, zolpidem) all worsen cognition, increase fall risk, and cause next-day hangover in elderly patients with dementia. Suvorexant has a fundamentally different safety profile.
• Dosing in Alzheimer’s: 10 mg one hour before bedtime; increase to 20 mg if needed. The Phase 3 dementia-specific RCT (PMID 37001521, Lancet Neurology 2023) showed significantly improved sleep time and reduced nighttime wandering vs. placebo, with no next-day sedation or worsening of cognition.
• Side effects: Somnolence, dream-like states, sleep paralysis (rare). Does not cause respiratory depression (important distinction from benzodiazepines). Can cause next-day impairment at higher doses.
• Drug interactions: CYP3A inhibitors (fluconazole, clarithromycin, grapefruit) increase suvorexant levels — use 5 mg in these combinations.

Medications to AVOID in Alzheimer’s

Music is one of the most potent non-pharmacological interventions in dementia care. Musical memory is processed by different brain circuits than episodic memory and often remains accessible even in severe dementia, when little else does.

• What it does: Reduces agitation, anxiety, and depression; improves mood and social engagement; can temporarily enhance autobiographical memory retrieval; reduces need for chemical restraint.
• Evidence: Multiple systematic reviews (Cochrane 2018 music therapy for dementia) confirm benefits for behavioral symptoms. Effect sizes are comparable to pharmacological interventions for agitation, with no side effects.
• How to use it at home: Create playlists from the person’s younger adulthood (the “reminiscence bump” period, roughly ages 15–25, produces the most emotionally resonant music). Use this music during high-stress transitions (bathing, dressing, mealtimes). Personalized playlists work better than generic “calming music.” The MUSIC & MEMORY program helps create individualized playlists; many memory care communities participate.
• Certified music therapists (MT-BC) can be engaged for structured sessions. Some hospice programs include music therapy as part of comfort care.

Reminiscence therapy uses photographs, familiar objects, music, and structured conversation to help people recall and share memories from earlier life. It is not about testing memory — it is about engaging the long-term memories that tend to be relatively preserved even into moderate dementia.

• Benefits: Improves mood, self-esteem, and social engagement; reduces agitation; supports the person’s sense of identity and continuity of self.
• Formats: One-on-one with a caregiver or therapist; small group (especially effective in adult day programs and memory care settings); digital life review using family photos assembled into a video or tablet app (apps like Udio are specifically designed for this).
• Creating a “memory book”: A simple, laminated book of 20–30 captioned photos from the person’s life can serve as an ongoing tool for engagement, orientation, and conversation. Include wedding photos, childhood family photos, pictures of pets, former homes, and work. Use large print captions.

Exercise is the most consistently evidence-supported intervention for slowing cognitive decline and reducing behavioral symptoms across all stages of dementia.

• Target: 150 minutes per week of moderate-intensity aerobic exercise (brisk walking, stationary cycling, swimming). Balance and strength training 2 days/week reduces fall risk.
• Evidence: The ADEX trial (PMID 27100309, Lancet Neurology 2016) showed 16 weeks of supervised aerobic exercise reduced neuropsychiatric symptoms including depression, anxiety, and irritability — with no significant adverse events. Walking programs specifically have shown consistent benefit across multiple dementia stages.
• Practical considerations: The person may need a walking partner for safety. Familiar routes reduce confusion. Exercise timing matters: morning exercise correlates with better nighttime sleep and less sundowning. Avoid vigorous exercise within 3 hours of bedtime.
• Chair-based exercise: When mobility becomes limited, chair yoga, seated stretching, and resistance bands maintain function and reduce fall risk.
• Tai chi: Strong evidence for fall prevention and balance; structured classes in community settings also provide social engagement.
• Caregiver involvement: Exercising together is one of the most effective strategies — it provides structure, supervision, and is beneficial for both parties.

An occupational therapist trained in dementia care can assess the home environment, identify safety risks, recommend adaptive equipment, and train caregivers in techniques that reduce conflict and increase independence. This is one of the highest-value specialist referrals in early-to-moderate dementia and is frequently underused.

• What an OT home assessment covers:
  • Fall hazards (throw rugs, poor lighting, clutter, stairs without rails)
  • Bathroom safety (grab bars, shower bench, raised toilet seat, non-slip mats)
  • Kitchen safety (stove auto-shutoff, sharp objects, medication access)
  • Wandering risk (door alarms, door knob covers, visual barriers)
  • Medication management systems
  • Adaptive equipment for dressing, grooming, eating
  • Caregiver body mechanics and safe-patient-handling techniques
• COPE intervention: The Care of Persons with Dementia in their Environments (COPE) is a structured OT program (PMID 22090487, JAMA IM 2012) showing that OT-led home assessment and caregiver training significantly reduced behavioral symptoms and improved caregiver confidence. Ask whether your area has COPE-trained OTs.
• Medicare coverage: OT home safety assessments are often Medicare-covered, particularly for homebound patients or following a hospitalization. Check with your plan.

Speech-language pathologists have two critical roles in Alzheimer’s care: supporting communication strategies as language declines, and assessing swallowing safety as dysphagia develops.

Communication strategies

• Use short, simple sentences — one idea at a time.
• Allow time for a response (10–15 seconds). The person is not ignoring you; processing is slow.
• Maintain eye contact at the same physical level. Crouch down rather than standing over.
• Never argue about facts. If someone insists it is 1965, you do not need to correct them. Meet the emotion: “That sounds wonderful. Tell me about it.”
• Avoid elderspeak (“sweetie,” “honey,” “good girl”) — it is infantilizing and increases agitation.
• Offer choices rather than open-ended questions: “Would you like the blue shirt or the green one?” rather than “What do you want to wear?”
• Use gestures and visual cues to supplement words.
• A communication board (pictures + simple words) can bridge the gap when word-finding becomes difficult.

Swallowing assessment

Dysphagia (swallowing difficulty) becomes increasingly common in moderate-to-advanced AD. An SLP can perform a clinical swallowing evaluation (CSE) and, when needed, a modified barium swallow study or FEES (fiberoptic endoscopic evaluation of swallowing) to characterize the type and severity of swallowing impairment.

• Signs of swallowing problems: coughing or choking during meals, wet or gurgly voice after eating, prolonged mealtimes, food or liquid coming out of the mouth, drooling, recurring chest infections, unexplained weight loss.
• The SLP can recommend food and liquid texture modifications following the IDDSI (International Dysphagia Diet Standardisation Initiative) framework — a standardized seven-level scale from thin liquids to regular food. This is the international standard replacing the older “nectar thick / honey thick” terminology.
• Thickened liquids reduce aspiration risk; texture-modified foods (minced and moist, pureed, etc.) are matched to the person’s swallowing ability. These modifications must be individualized — over-thickening reduces fluid intake and can cause dehydration.

Adult day programs provide structured daytime activities (social, cognitive, recreational, sometimes physical therapy) in a group setting outside the home. They are one of the most effective, underused supports in moderate dementia.

• Benefits for the person: Social stimulation, structured routine, skilled supervision, reduced isolation.
• Benefits for caregivers: Predictable time off, return to part-time work, reduced burnout. Studies show that adult day use is one of the strongest predictors of delaying nursing-home placement.
• Find programs via the Eldercare Locator (eldercare.acl.gov), your local Alzheimer’s Association chapter, or area agency on aging. In Utah: contact the Utah Department of Health and Human Services Aging and Adult Services (1-877-424-4640).
• Medicare generally does not cover adult day programs (except through PACE and some Medicare Advantage plans). Medicaid waivers often do. Some states have specific funding programs for dementia-specific day services.

In-home respite — trained caregivers who come to the home so the family caregiver can take breaks. The National Respite Locator (archrespite.org) and ARCH (Administration for Community Living) network can help find local providers. Costs vary; some Medicaid waivers, VA caregiver programs, and Alzheimer’s Association chapters offer subsidized respite.

Short-term inpatient respite — placement in a memory care or skilled nursing facility for 1–4 weeks to allow the caregiver to travel, recover from illness, or simply rest. Medicare Part A covers up to 5 days of inpatient respite care for hospice-eligible patients; outside hospice, this is typically self-pay or Medicaid.

• Stove / kitchen: Automatic stove shut-off devices (available online, ~$30–100) cut power after a set time without a touch. Disable the burners for a person who is alone or routinely forgets food on the stove. Remove or lock sharp utensils when no longer safe to use independently. Lock cabinets containing medications, cleaning products, and alcohol.
• Doors and wandering: Install door alarms (sensor alerts when exterior doors open). Door knob covers, slide-bolt locks placed high or low (where they are less visible), and camouflage door covers (making an exit door look like a bookshelf or wall) are all effective. Register with the Alzheimer’s Association Safe Return program and/or local Project Lifesaver (GPS ankle bracelet, law-enforcement monitored). Consider a medical-alert ID bracelet with name, condition, and emergency contact — MedicAlert Foundation partners with the Alzheimer’s Association.
• Bathroom: Grab bars on the wall beside the toilet and in the shower (screw-mounted into studs, not pressure-mounted; a fall against an improperly mounted bar is dangerous). Non-slip mat inside and outside the shower. Shower bench or transfer bench. Raised toilet seat with armrests. Set water heater to ≤120°F to prevent scalding. Consider a walk-in shower conversion if stairs into a tub are a fall risk.
• Lighting: Motion-activated nightlights in the hallway, bathroom, and bedroom — night-time trips to the bathroom are a major fall risk. Replace dim bulbs throughout. Avoid dramatic shadows (a dark area can be perceived as a step or hole by someone with spatial processing impairment).
• Falls: Remove throw rugs. Secure loose electrical cords. Install handrails on both sides of all stairs. Consider stair gates if stair use is unsafe. Non-slip socks or slippers with rubber soles. Review all medications for fall-increasing side effects (alpha-blockers, antihypertensives causing orthostatic hypotension, benzodiazepines, antihistamines).
• GPS devices: Wearable GPS trackers designed for dementia are available (AngelSense, Apple Watch with Family Sharing, Samsung Galaxy Watch with Care Manager, dedicated GPS shoes). These allow real-time location tracking via smartphone app. Discuss openly with the person while they can understand — it is a safety tool, not surveillance.
• Medications: Automatic pill dispensers with alarms, blister packs, and dosette boxes reduce medication errors. Some electronic dispensers (e.g., MedMinder) lock unused doses and alert caregivers if a dose is missed. Consider transferring all medication management to the caregiver when errors become common.
• Financial safety: Restrict credit cards and checkbook access; consider a credit monitoring service. Scams targeting older adults with dementia are rampant — set up call blocking for unknown numbers, create a low-limit debit card for daily purchases, and name a trusted family member as a second signer on accounts.

Driving is a potent symbol of independence, and discussing cessation triggers enormous emotional resistance. But dementia is a progressive brain disease that impairs the executive function, reaction time, spatial processing, and attention that driving requires. Most people with dementia will need to stop driving well before they feel ready.

• Who should assess driving: The treating physician can document clinical concerns. But a formal driving rehabilitation evaluation by a Certified Driver Rehabilitation Specialist (CDRS) is the most objective, defensible approach. They conduct behind-the-wheel testing — not just cognitive testing. Find a CDRS through the Association for Driver Rehabilitation Specialists (ADED) at aded.net or via the AAA Roadwise program.
• Red flags that driving must stop now: Recent at-fault accident or near-miss; getting lost in familiar areas; running stop signs or lights; passenger fear; police contact for driving behavior; inability to respond appropriately to unexpected road events; CDR Global Score ≥1 in most specialist opinion.
• State reporting: Some states (California, Delaware, Nevada, Oregon, Pennsylvania) require physicians to report dementia to the DMV, which may then revoke or restrict the license. In most states, reporting is optional. The treating physician can write a letter recommending cessation that the family can use with the DMV. The family can also request a voluntary surrender of the license.
• Practical steps for the family: If the person refuses to stop, hide car keys (or disconnect the battery / fuel fuse), involve the physician (a doctor’s “prescription” to stop driving is often better accepted than a family decree), or request a DMV letter. Do not get into prolonged arguments — redirect to the alternative transportation plan.
• Transportation alternatives: AAA SeniorDriving.AAA.com has resources by state. Lyft/Uber (with family setup on their phone or GoGoGrandparent 1-855-464-6872, a phone-based rideshare service for older adults who do not use smartphones). Local Area Agency on Aging transport programs. Volunteer driver programs (ITNAmerica). AARP CarFit program helps optimize vehicle safety in the transition period.

The most common regret families express is not doing this early enough. By the time moderate dementia is established, the person may no longer have legal capacity to sign documents — meaning the family must go through expensive and difficult court guardianship proceedings to manage the person’s affairs.

Durable Power of Attorney for Finances (DPOA-F)

Authorizes a trusted person (agent) to manage financial affairs — pay bills, manage investments, sell property, file taxes — on the person’s behalf. Durable means it remains valid even after the person loses capacity. A regular (non-durable) POA terminates at incapacity — exactly when you need it most. Execute this NOW, in the mild stage. Requires the person to have legal capacity to sign (understands the document and the consequences).

Durable Power of Attorney for Healthcare (DPOA-HC) / Healthcare Proxy

Designates a healthcare agent to make medical decisions if the person cannot make them for themselves. This is the single most important document for medical care decisions later in the disease. It must be signed while the person has capacity. It is different from a living will (which states personal preferences) — the DPOA-HC names a person who can respond to unforeseen situations.

Advance Directive / Living Will

A document in which the person states their own preferences for medical treatment — what interventions they do and do not want if they cannot speak for themselves. Should address: CPR (resuscitation), mechanical ventilation, artificial hydration and nutrition (feeding tube), hospitalization vs. home care, dialysis, and, ultimately, comfort-focused care. Many states have combined forms that serve as both living will and healthcare proxy designation. Download state-specific forms at CaringInfo.org (National Hospice and Palliative Care Organization).

POLST (Physician Orders for Life-Sustaining Treatment) or MOLST

A medical order — signed by a physician or NP/PA, not just the patient — that translates advance care preferences into actionable medical orders. Unlike an advance directive (a legal document), a POLST is a medical order that EMS and hospital staff are legally required to honor. It should be created when the person has a serious illness and is at risk of a medical emergency. In Utah, the POLST (also called MOST — Medical Orders for Scope of Treatment in some Utah facilities) form is available through the Utah Medical Association. Place a copy on the refrigerator door (standard EMS location), in the medical chart, and in the hospital go-bag.

Will and Estate Review

If the person has assets, a will, trust, and beneficiary designations should be reviewed and updated. This is especially important for blended families, estranged relatives, or assets held jointly. An estate attorney can ensure the will is legally valid, trusts are properly funded, and beneficiary designations on 401(k)s, IRAs, and life insurance policies are current.

Social Security Disability

For people younger than retirement age with Alzheimer’s, Social Security Disability Insurance (SSDI) may be available. Alzheimer’s disease qualifies as a Compassionate Allowance condition under the SSA — applications are typically fast-tracked. For individuals 65+, standard Social Security retirement benefits are not impacted by the diagnosis.

Long-Term Care Planning

Memory care costs in the US average $5,000–8,000/month (2025 data). Medicare does not cover custodial (non-medical) care in nursing homes or memory care communities. Planning options include: existing long-term care insurance policies, Medicaid (requires spending down assets in most states; consult an elder law attorney for legal spend-down strategies), VA Aid and Attendance benefits for veterans, and life insurance conversion options (life settlements, hybrid long-term care policies). An elder law attorney specializing in Medicaid planning can be invaluable — the rules are complex and vary by state.

Finding an Elder Law Attorney

National Academy of Elder Law Attorneys (naela.org) has a directory. Many local Alzheimer’s Association chapters can provide referrals. Some offer reduced-fee consultations for limited-income families.

The MIND diet (Mediterranean-DASH Intervention for Neurodegenerative Delay) combines elements of the Mediterranean and DASH diets with specific emphasis on foods associated with brain health. Observational studies suggest that close adherence to the MIND diet is associated with slower cognitive decline and lower dementia risk. A randomized trial (MIND Trial, published NEJM 2023) did not demonstrate significant slowing of cognitive decline in a general population, but the dietary pattern remains broadly recommended as part of cardiovascular and brain health optimization.

• Emphasize: Leafy green vegetables (kale, spinach, lettuce — at least 6 servings/week); other vegetables (≥1 serving daily); berries (blueberries and strawberries especially — ≥2 servings/week); nuts (≥5 servings/week); olive oil (primary cooking oil); whole grains (≥3 servings/day); fish (≥1 serving/week); beans (≥4 meals/week); poultry (at least 2 servings/week).
• Limit: Red meat, butter/margarine (<1 tbsp/day), cheese (<1 serving/week), pastries and sweets (<5 servings/week), fried/fast food (<1 serving/week).
• Hydration: Dehydration is a common and under-recognized cause of behavioral worsening and delirium in dementia. Aim for 6–8 glasses (48–64 oz) of fluid daily. People with dementia often lose the sense of thirst — offer fluids proactively on a schedule, not just when asked.
• Appetite changes: Weight loss is very common in moderate-to-advanced Alzheimer’s (metabolic acceleration + appetite loss + swallowing difficulty). High-calorie, nutrient-dense foods are more important than dietary restrictions at this stage. Consider nutritional supplements (Ensure, Boost) when weight loss is significant. A registered dietitian referral can help.
• Mealtime strategies: Reduce distractions (turn off the TV, clear the table of clutter). Use contrasting plate colors (a white plate on a white tablecloth is hard for people with visual-spatial impairment to see). Provide finger foods when utensils become difficult. Serve smaller, more frequent meals. Sit beside the person during meals rather than across from them.

• How is the disease progressing relative to what you’d expect? Faster, slower, or about on track?
• Are all three cholinesterase inhibitors available to us, and which do you recommend for this stage and why?
• Should we be adding memantine now? What is the right timing?
• Are any of the current medications likely to be worsening cognition or behavior (anticholinergics, sedatives)?
• Is a referral to geriatric psychiatry or behavioral neurology appropriate for the behavioral symptoms?
• What do you recommend trying first for the agitation — environmental changes, an antidepressant like escitalopram, or something else?
• Is brexpiprazole an option for this person’s agitation, and what would that conversation look like?
• What can we do for the sleep disruption without using a benzodiazepine? Can we discuss suvorexant?
• Should we request a formal driving evaluation by a CDRS?
• Who should we see for an OT home safety assessment, and is that covered by Medicare?
• Are there local adult day programs or caregiver support groups you recommend?
• Are there clinical trials this person would be eligible for?
• Are we enrolled or eligible for the Medicare GUIDE dementia care program?
• What is your estimate of what the next 12–18 months will look like, and what should we be preparing for?

Caregiving in the mild-to-moderate stage is often the most emotionally complex period of the entire journey. The person is still present enough to grieve their own losses, argue about safety, resist help, and have moments of lucidity that make denial tempting — and then moments of profound confusion that make the reality undeniable.

• You are managing grief while caregiving. This is called ambiguous loss — grieving someone who is still physically present. Your feelings of anger, sadness, resentment, and love are all valid. Grief counseling during this phase (not just at end of life) is underused and genuinely helpful. Ask your own doctor for a referral.
• The legal and financial work cannot wait. This is the window. If you delay until the moderate stage, you may lose the ability to do this cleanly. Get the DPOA-F, DPOA-HC, advance directive, and POLST done now. Every elder law attorney has stories about families who waited.
• Build your team, not just a care plan. A good care team includes: the neurologist or geriatrician, a primary care doctor who knows the person, a social worker or care manager, an OT, possibly an SLP, and an elder law attorney. You should not be navigating this alone.
• Be strategic about what you correct. Constantly correcting someone who is confused and frightened is exhausting for you and distressing for them. Use “therapeutic fibbing” selectively — meeting the person in their reality rather than insisting on yours. This is not dishonesty; it is compassion. If they ask for a parent who died decades ago, it is okay to say “They’re not here right now. You’re safe. Tell me about them.”
• Document behavioral changes. Keep a brief written log of behavioral symptoms, their timing, what preceded them, and what helped. This is invaluable at clinic visits and helps identify patterns (late afternoon = sundowning, Thursdays are harder because of schedule change, etc.).
• Respite is not abandonment. Using adult day programs, in-home help, or short inpatient stays is not giving up. It is the only sustainable path for long-term caregiving. Caregivers who burn out are not able to provide care at all.
• Stay connected to your own life. Maintain at least one regular activity — a walk, a coffee with a friend, a weekly class — that is yours. Caregiver isolation is a risk factor for depression, cardiovascular disease, and cognitive decline. You are not expendable.
• Know the warning signs of caregiver crisis: Not sleeping, persistent sadness, feeling unable to cope, neglecting your own health, thoughts of harming yourself or the person you care for — these are emergencies. Call 988 (Suicide and Crisis Lifeline), your own doctor, or the Alzheimer’s Association 24/7 helpline (1-800-272-3900).

Understanding what is medically expected in advanced Alzheimer’s helps families recognize that these changes are part of the disease trajectory — not failures of care.

• Profound memory loss: The person may not recognize spouse, children, or close family. They live almost entirely in the present moment. Long-term memories (early life) may persist as fragments but cannot be reliably communicated.
• Loss of language: Speech typically reduces to single words, brief phrases, echolalia (repeating what is said to them), or becomes entirely absent. Communication shifts to non-verbal channels: facial expression, eye contact, reaching, sounds.
• Mobility loss: Progressive loss of ability to walk; eventually cannot stand or turn in bed without assistance. Contractures (fixed joint bending, especially in hands and arms) develop from muscle shortening when mobility is lost — prevented/reduced by passive range-of-motion exercises daily and splinting when appropriate.
• Incontinence: Both bladder and bowel incontinence are nearly universal by this stage. Scheduled toileting (every 2 hours during waking hours) is more effective and more dignified than waiting for accidents. Absorbent undergarments; careful skin care to prevent moisture-associated skin breakdown; avoid urinary catheters except when truly necessary (they increase infection risk and are uncomfortable).
• Dysphagia (swallowing difficulty) — see detailed section below.
• Weight loss: Even with adequate feeding assistance, significant weight loss is typical in advanced dementia. This is largely metabolic — the brain uses enormous energy, and this is disrupted as it fails. Do not interpret weight loss alone as inadequate feeding.

Dysphagia in advanced Alzheimer’s is neurologically driven — the brain can no longer coordinate the complex reflex chain of swallowing. Aspiration pneumonia — when food or liquid enters the lungs instead of the stomach — is the leading cause of death in advanced Alzheimer’s. This is a disease complication, not a failure of caregiving.

IDDSI Texture and Thickness Framework

The International Dysphagia Diet Standardisation Initiative (IDDSI) provides a standardized seven-level framework for food texture and liquid thickness. Your speech-language pathologist will use this to specify the appropriate level:

• Liquids (Levels 0–4): 0 = Thin (regular water); 1 = Slightly Thick; 2 = Mildly Thick (nectar-like); 3 = Moderately Thick (honey-like); 4 = Extremely Thick (pudding-like).
• Foods (Levels 3–7): 3 = Liquidised; 4 = Pureed; 5 = Minced and Moist; 6 = Soft and Bite-Sized; 7 = Regular.
• Over-thickening liquids reduces oral intake and increases dehydration risk — the goal is the least restrictive texture that allows safe swallowing.
• Re-evaluate dysphagia management regularly, as the person’s swallowing ability changes over time.

The Evidence Against Percutaneous Endoscopic Gastrostomy (PEG) Feeding Tubes

Feeding tubes are one of the most common medical interventions recommended to families of people with advanced dementia — and one that the strongest evidence consistently argues against.

Why feeding tubes don’t help: Aspiration in advanced dementia often occurs on saliva, not food. A feeding tube does not eliminate the aspiration of oral secretions. Tube feeding can cause aspiration of stomach contents (reflux). It is associated with agitation (because of the discomfort), restraint use (to prevent self-removal of the tube), pressure injuries (from immobility around tube care), infections (tube-site infections, aspiration from reflux), and diarrhea.

What does help: Careful, patient, person-centered hand-feeding for comfort and pleasure, even if caloric intake is limited. Small amounts of favorite foods provided by a person who speaks softly, makes eye contact, and gives adequate time between bites. This approach honors the social and sensory dimensions of eating — the ritual of shared meals — even when the nutritional goal has shifted to comfort rather than sustenance. A speech-language pathologist can advise on positioning and pacing techniques to minimize aspiration risk during hand-feeding.

Aspiration pneumonia is the most common immediate cause of death in advanced dementia. When it occurs, the family and medical team face one of the most consequential goals-of-care conversations in the illness: treat aggressively with hospitalization and IV antibiotics, or provide comfort-focused management at home or in the current care setting?

• Hospitalization harms in advanced dementia: Hospital environments are highly disorienting for people with severe dementia — the unfamiliar surroundings, noise, painful procedures, IV lines, and restraints can cause profound suffering. Delirium (acute confused state from hospitalization itself) is almost universal. Discharge to a care facility rather than home is common after hospitalization.
• Comfort-focused antibiotic treatment at the care setting: For patients whose goals are comfort, oral antibiotics (when the person can still swallow) or subcutaneous antibiotics (for home/hospice) can treat pneumonia adequately without hospitalization. If the person cannot swallow tablets, hospice can provide injectable or liquid antibiotics as appropriate to goals.
• The goals-of-care conversation: The POLST/MOLST created earlier in the illness should guide this decision. If the POLST specifies comfort measures only, aggressive hospitalization and IV antibiotics are inconsistent with the person’s stated preferences. The POLST is a legal medical order that should be honored.
• When there is no POLST: The healthcare proxy (designated in the DPOA-HC) makes this decision. They are legally and ethically obligated to make the decision the person would have made, not the decision the proxy would make for themselves. The medical team can and should advise on what the evidence shows about likely outcomes of different treatment paths.

When mobility is severely limited, pressure injuries (formerly called pressure ulcers or bedsores) become a serious concern. They cause significant pain and can be life-threatening if they become infected. Prevention is far more effective than treatment.

• Repositioning: Turn and reposition the person at least every 2 hours if bedbound; every 1 hour if sitting in a wheelchair. Keep a repositioning log to maintain consistency across all caregivers and shifts.
• Pressure-redistributing surfaces: Foam alternating-pressure mattresses (available via medical supply companies and often covered by Medicare Part B for at-risk patients) significantly reduce pressure injury incidence. Wheelchair cushions (gel or foam) for patients who spend time sitting.
• Skin inspection: Inspect all bony prominences daily (heels, sacrum, hips, elbows, shoulders, back of head). Early signs: persistent redness that does not blanch with fingertip pressure. Act immediately — once skin breaks down, healing is very slow in frail elders.
• Skin care: Keep skin clean and dry, particularly in the perineal area (incontinence contact). Use a moisture barrier cream (zinc oxide, dimethicone-based products) to protect from moisture-associated skin damage. Avoid vigorous rubbing; pat dry.
• Nutrition and hydration: Adequate protein intake (1.2–1.5 g/kg/day) supports skin integrity. Dehydration increases pressure injury risk significantly.
• Heel protection: Heels are particularly vulnerable; elevate them off the bed surface with foam wedge boots or pillow placement under the calves.

People with advanced dementia often cannot report pain verbally — but pain is common, frequently undertreated, and one of the most common drivers of behavioral disturbance. Agitation, resistance to care, crying out, grimacing, and restlessness in someone with advanced dementia are pain until proven otherwise.

PAINAD Scale (Pain Assessment in Advanced Dementia)

A validated observational tool to assess pain in non-verbal patients. Score each item 0–2; total 0–10 (higher = more severe pain). Items assessed over a 5-minute observation:

• Breathing (independent of vocalization): 0 = normal; 1 = occasional labored breathing or short periods of hyperventilation; 2 = noisy labored breathing, long period of hyperventilation, Cheyne-Stokes respirations
• Negative vocalization: 0 = none; 1 = occasional moans or groans, low-level speech with negative/disapproving quality; 2 = repeated troubled calling out, loud moaning or groaning, crying
• Facial expression: 0 = smiling or inexpressive; 1 = sad, frightened, frown; 2 = facial grimacing
• Body language: 0 = relaxed; 1 = tense, distressed pacing, fidgeting; 2 = rigid, fists clenched, knees pulled up, pulling or pushing away, striking out
• Consolability: 0 = no need to console; 1 = distracted or reassured by voice or touch; 2 = unable to console, distract, or reassure

Interpretation: Score 1–3 = mild pain; 4–6 = moderate pain; 7–10 = severe pain. A score ≥4 should prompt analgesic treatment.

Pain management approach

• First line: scheduled acetaminophen. Regular-dose acetaminophen 650 mg three times daily (or 500 mg four times daily) — not just as-needed. Studies show that scheduled acetaminophen reduces agitation and behavioral disturbance in advanced dementia more than as-needed dosing. Maximum dose 2,000 mg/day in elderly patients (less if hepatic impairment or moderate alcohol use).
• Topical agents: For localized musculoskeletal pain (arthritis, contracture pain), topical diclofenac gel or lidocaine patches are effective without systemic effects.
• Opioids: Appropriate for moderate-to-severe pain, particularly in hospice settings. Low-dose oral morphine (2.5–5 mg every 4–6 hours) is effective and can improve comfort without meaningfully shortening life when used appropriately. The myth that opioids accelerate death when used correctly for pain is not supported by evidence. Hospice nurses and palliative care teams are expert in opioid titration for advanced dementia.
• NSAIDs: Use with extreme caution in frail elders. GI bleeding, renal injury, and cardiovascular risks are amplified. If used at all, use the lowest dose for the shortest duration with a GI protectant (PPI).

Agitation in advanced dementia has many possible causes and should be systematically investigated before reaching for medications.

Check for:

• Pain — use PAINAD, and if pain is suspected, give a scheduled acetaminophen trial for 3–5 days before attributing behavior to dementia alone.
• Urinary retention or full bladder — a very common and easily addressed cause.
• Constipation and bowel impaction — check for last bowel movement; abdominal palpation. Bowel impaction causes extreme distress and agitation.
• Infection — UTI, pneumonia, skin infection. Check vital signs; low-grade fever may be the only sign.
• Dehydration — skin turgor, mucous membranes, urine output.
• Environmental factors — overstimulation (TV, noise, too many people), understimulation (boredom, isolation), unfamiliar environment or caregiver.
• Medication side effects — review the medication list with the physician.
• Unmet emotional needs — fear, loneliness, loss of routine. Presence, touch, calm voice, and familiar music can address these.

Non-pharmacological approaches to try before medication: music from the person’s life, hand massage or gentle touch, rocking motion, warm bath or shower, walking (if ambulatory), involvement in a simple repetitive task (folding towels, sorting objects), redirecting attention.

If medication is required after non-pharmacological measures have been tried: low-dose antipsychotics (risperidone 0.25–0.5 mg/day is the best-evidence option for severe agitation/psychosis in dementia) or escitalopram (CitAD evidence); brexpiprazole can also be used at this stage. Discuss risks and benefits with the medical team; document that non-pharmacological approaches were tried.

Hospice is one of the most beneficial and most underused services in advanced dementia. People with dementia are enrolled in hospice on average for only 3–4 weeks before death — compared to 6 months for cancer — despite evidence that earlier enrollment leads to better symptom management, fewer hospitalizations, less family distress, and often longer survival.

Who qualifies for hospice?

Medicare Hospice Benefit criteria for dementia: Two physicians certify that life expectancy is ≤6 months if the disease runs its expected course. The dementia functional staging tool used is the FAST (Functional Assessment Staging Tool). Hospice eligibility for dementia typically requires:

• FAST Stage 7c or beyond: The person cannot ambulate without substantial assistance (7a), cannot sit up independently (7b), has lost all purposeful verbal ability — no more than 1–5 intelligible words per day (7c), has lost the ability to smile (7d), and has lost the ability to hold their head up independently (7e–f).
• Plus at least one of the following co-morbid conditions in the prior 12 months: aspiration pneumonia, pyelonephritis (kidney infection), septicemia, multiple stage 3–4 pressure injuries, fever after antibiotics, inability to maintain fluid or caloric intake (with ≥10% body weight loss in 6 months, or serum albumin <2.5 g/dL).

Important: You do not need to meet all FAST criteria perfectly to enroll. If your clinician believes prognosis is ≤6 months based on the overall clinical picture, they can certify hospice eligibility. If the patient stabilizes, hospice can be continued with re-certification every 60–90 days.

What Medicare Hospice covers

The Medicare Hospice Benefit (Part A) covers essentially everything related to the hospice diagnosis:

• Skilled nursing visits (usually 1–3 times per week, daily if needed near death)
• Physician oversight (hospice medical director)
• Social worker visits
• Chaplaincy and spiritual care
• Home health aide assistance (bathing, personal care)
• All medications related to the hospice diagnosis (pain, anxiety, secretions, etc.) — no copays
• Medical equipment (hospital bed, wheelchair, bedside commode, oxygen, etc.) — delivered to the home
• Inpatient respite care (up to 5 days at a time in a facility)
• Inpatient hospice care for uncontrolled symptoms that cannot be managed at home
• Bereavement support for the family for 13 months after death

The tradeoff: Enrolling in hospice means electing the comfort benefit — forgoing curative or life-prolonging treatment for the primary hospice diagnosis. Treatments for other conditions (e.g., blood pressure medication) can continue. A hospitalization for pneumonia with aggressive IV treatment would be inconsistent with hospice enrollment; the family and hospice team would need to “revoke” hospice for that hospitalization and then re-enroll afterward.

Debunking hospice myths

• “Hospice means giving up.” Hospice is a philosophy of care, not abandonment. It is an active, skilled medical service focused on quality of life. Many families describe hospice enrollment as the first time they felt truly supported in the caregiving role.
• “Hospice will accelerate death.” This is not true. Multiple studies have found that hospice enrollment does not shorten and may modestly extend life, likely because of better symptom management, fewer harmful hospital interventions, and more attentive daily care. Landmark studies in JAMA (PMID 17400922) and NEJM have supported this finding.
• “You can’t come back from hospice.” You can. If a patient improves significantly (this does happen, particularly in dementia where the 6-month prognosis is inherently uncertain), they can be discharged from hospice and return to curative care. This is called “live discharge” and occurs in roughly 15–20% of dementia hospice enrollments.
• “We have to wait until the last few days.” Families who enroll when death is days away miss most of the benefit. Months of hospice support creates a very different experience for both the patient and family than a few days.

How to access hospice

Ask the treating physician for a hospice referral, or contact a hospice agency directly (they can evaluate eligibility themselves). The Alzheimer’s Association (1-800-272-3900) can help identify reputable local hospice providers. The National Hospice and Palliative Care Organization (CaringInfo.org) has a free hospice locator and advance directive forms.

Palliative care and hospice are not the same thing, though they share the same principles of comfort and quality of life.

• Palliative care: A specialized medical approach focused on symptom relief, quality of life, and support for patients and families at any stage of a serious illness — it can begin at diagnosis and run alongside disease-modifying or curative treatment. A palliative care team (physician, nurse, social worker, chaplain) consults on pain management, communication, goals of care, and family support. Increasingly available via telehealth. Covered by Medicare Part B as outpatient specialty care, and often by inpatient DRG when consulted in the hospital.
• Hospice: A specific form of palliative care for people with a ≤6-month prognosis who have elected to stop curative treatment for their terminal diagnosis. Covered under the Medicare Hospice Benefit (Part A).
• The practical advice: Ask for a palliative care referral early — in the moderate stage, or when difficult symptoms arise. Do not wait until the very end. Palliative care can prepare the family for what is ahead, help with goals-of-care conversations before they become crises, and improve symptom management throughout the advanced stage.

Advanced dementia brings a series of decision points that families often reach without preparation. The most important of these — hospitalization for pneumonia, feeding tube decisions, CPR, antibiotics for the last infection — are much less agonizing when the person’s values and preferences were documented earlier.

The POLST/MOLST (created ideally in the mild-to-moderate stage) translates those preferences into medical orders. At the advanced stage, it should specify:

• CPR: Yes or No (in advanced dementia, successful CPR leaving a meaningful quality of life is exceedingly rare)
• Level of medical intervention: Full treatment / Limited additional interventions (no CPR but hospitalize if needed) / Comfort-focused (treat symptoms only; avoid hospitalization)
• Artificial nutrition: Yes / Trial period only / No
• Antibiotics: Use to treat infections / Use only if necessary for comfort / No antibiotics

If the family did not create a POLST earlier, this conversation must happen now with the medical team. The healthcare proxy makes these decisions based on what they know about the person’s values and prior expressed wishes. When no DPOA-HC exists and the family disagrees, hospital ethics committees can be consulted.

Dementia caregivers have among the highest rates of psychological distress of any caregiver group. Studies consistently find that 40–70% of dementia caregivers meet criteria for clinical depression, with anxiety nearly as prevalent. The physical toll is also significant: caregivers have higher rates of cardiovascular disease and earlier mortality than non-caregivers.

Anticipatory grief

Grief in dementia begins long before death — sometimes years before. You are grieving the person as they were, the relationship you had, the future you imagined, and the slow erosion of who they were. This is called anticipatory grief or ambiguous loss (grief for someone still physically present). It is real grief. It is normal. It is not a sign that you have “given up.”

• Seek grief counseling before bereavement, not just after. Most hospice programs offer grief counseling to the family during the caregiving phase, not just after death.
• Caregiver support groups (in-person through local Alzheimer’s Association chapters; online through ALZConnected) connect you with people who understand in ways that friends and family who have not lived this may not.
• Allow yourself to feel both love and exhaustion simultaneously. These are not contradictions.

Respite options in the advanced stage

• Medicare Hospice Benefit inpatient respite: Up to 5 consecutive days of inpatient respite at a Medicare-certified facility (nursing home, inpatient hospice, hospital) — covered fully by Medicare for hospice-enrolled patients. Can be repeated as needed.
• In-home hospice aide: Hospice typically includes several hours/week of home health aide assistance. Ensure you are using the full benefit; some families underuse it.
• Memory care short-stay / respite beds: Many memory care communities offer short-term stays (1–4 weeks) at daily rates. This allows a caregiver to travel, recover from illness, or rest. Cost is typically self-pay or Medicaid (where waivers cover it).
• VA Caregiver Support Program: For veteran-patients, the VA has significant caregiver support including training, stipends (Program of Comprehensive Assistance for Family Caregivers), and respite through the Program of General Caregiver Support Services. Call 1-855-260-3274.

Post-death grief and bereavement

Grief after the death of someone with dementia is complicated by the prolonged anticipatory grief, by the sense of relief that is almost universal (and is a normal, healthy response to the end of suffering — not a failure of love), and sometimes by a delayed grief response (some caregivers describe not feeling grief until months after the death, when the adrenaline of caregiving finally wears off).

• The Medicare Hospice Benefit includes 13 months of bereavement support for the family after the patient’s death — including counseling and support groups. Use it.
• The Alzheimer’s Association (1-800-272-3900) provides grief support and can connect families to local bereavement counselors.
• If grief is accompanied by prolonged inability to function, thoughts of self-harm, or persistent inability to experience anything positive, seek professional mental health support. Complicated grief disorder (prolonged grief disorder) is a clinical entity that responds to specific evidence-based therapies.
• The 988 Suicide and Crisis Lifeline (call or text 988) is available 24/7 for any caregiver in crisis.
• Local community hospice bereavement programs, grief groups at religious communities, and therapists specializing in health-related grief are all resources worth seeking.

• Is this person eligible for hospice? If not now, what would need to change?
• What do you realistically think the next 3–6 months will look like?
• Which of the current medications should we consider stopping? What are we still achieving with the cholinesterase inhibitor / memantine at this stage?
• How should we assess for pain when the person cannot tell us they hurt?
• What is the right approach to the swallowing difficulty — should we see an SLP, and what texture/liquid level would you recommend?
• If aspiration pneumonia develops, what would you recommend for treatment in the context of this person’s care goals?
• Is there a POLST in place? If not, can we complete one now?
• How should we manage the agitation without antipsychotics — what would you try first?
• What signs of pain or discomfort should we watch for, and what should we do when we see them?
• What support does the hospice team provide for caregivers?
• Are there palliative care resources we can access now, even before hospice eligibility?
• What does death from advanced Alzheimer’s typically look like, and how will we know when it is very close? What should we do in the last days and hours?

• Trial: CLARITY-AD (NCT03887455)
• Drug: Lecanemab (Leqembi), Eisai/Biogen
• Phase: Phase 3, randomized, double-blind, placebo-controlled
• Population: 1,795 adults with MCI due to Alzheimer's or mild Alzheimer's dementia; amyloid-confirmed by PET or CSF
• Primary endpoint: CDR-SB (Clinical Dementia Rating Sum of Boxes) at 18 months
• Result: 27% slowing of clinical decline on CDR-SB (0.45-point difference; 1.66 vs 1.21); highly statistically significant (p<0.001)
• ARIA-E: 12.6% of lecanemab-treated patients vs 1.7% placebo. Symptomatic ARIA: 2.8% vs 0%.
• ARIA-H: 17.3% vs 9.0%
• Publication: van Dyck et al., NEJM 2023;388:9–21. PMID 36449413
• Outcome: Led to traditional FDA approval July 6, 2023.

• Trial: TRAILBLAZER-ALZ 2 (NCT04437511)
• Drug: Donanemab (Kisunla), Eli Lilly
• Phase: Phase 3, randomized, double-blind, placebo-controlled
• Population: 1,736 adults with symptomatic early Alzheimer's (MCI or mild dementia); amyloid-confirmed by PET; tau burden stratified
• Result: In the low/medium tau population: 35% slowing on iADRS. Across the full population: 22% slowing. CDR-SB slowing: 36% in low/medium tau; 29% overall.
• Treatment stop: Donanemab was stopped when amyloid PET reached <11 Centiloids. 52% of treated patients reached this threshold by 12 months; 72% by 18 months.
• ARIA-E: 24.0% donanemab vs 2.1% placebo. Symptomatic ARIA-E: 6.1% vs 0.3%. Three treatment-related deaths reported.
• Publication: Sims et al., JAMA 2023;330(6):512–527. PMID 37459141
• Outcome: Led to traditional FDA approval July 2, 2024.

• Trial: TRAILBLAZER-ALZ 6 (NCT05738486)
• Drug: Donanemab only — a Phase 3b study comparing four different dosing/titration regimens (not a comparison against another drug)
• Phase: Phase 3b (843 participants, 4 arms)
• Primary endpoint: Incidence of ARIA-E by titration regimen, with amyloid clearance as a key secondary
• Status: Reported — the modified titration (350 → 700 → 1050 → 1400 mg) cut ARIA-E by ~41% at 24 weeks (13.7% vs 23.7% with standard dosing) while achieving comparable amyloid clearance. This modified schedule is now reflected in donanemab’s use. (Note: a separate trial, TRAILBLAZER-ALZ 4 / NCT05108922, compared donanemab head-to-head against aducanumab — not lecanemab.)

• Trial: AHEAD 3-45 (NCT04468659) — A45 and A3 sub-studies
• Drug: Lecanemab, Eisai/Biogen
• Phase: Phase 3, prevention trial in cognitively normal adults
• Population: Adults ages 55–80 with intermediate or elevated brain amyloid but no symptoms. The largest Alzheimer's prevention trial ever conducted.
• Primary endpoint: Change in brain amyloid (A3) and cognition via the PACC-5 (A45)
• Status: Enrolling globally. Results expected approximately 2027–2028.

• Trial: EVOKE and EVOKE+ (NCT04777396)
• Drug: Semaglutide (oral Rybelsus, 14 mg), Novo Nordisk
• Phase: Phase 3, randomized, placebo-controlled
• Population: ~3,700 adults with early Alzheimer's (MCI or mild dementia)
• Result: Top-line results reported in 2025 showed the trial did not meet its primary endpoint. Semaglutide was not statistically superior to placebo on CDR-SB at 156 weeks. Semaglutide is not recommended as an Alzheimer's treatment based on current evidence.

• BIIB080 (diranersen, tau antisense oligonucleotide) — Biogen/Ionis. Intrathecally administered ASO that reduces tau production. Phase 2 data (2024) showed significant reductions in CSF tau biomarkers; Phase 3 design being finalized.
• UCB0107 (anti-tau antibody) — UCB Biosciences. Phase 2 trial in early Alzheimer's. Ongoing. Results expected 2026–2027.
• Semorinemab (anti-tau mAb) — Roche/AC Immune. Phase 2 LAURIET trial in mild-moderate Alzheimer's; development continuing in MCI population.
• Why this matters: Combination therapy targeting both amyloid and tau simultaneously may be the future of Alzheimer's treatment — analogous to how HIV is now treated with multi-drug regimens.

• Lecanemab (Leqembi): Traditional approval granted July 6, 2023. Subcutaneous maintenance formulation FDA-approved August 2025.
• Donanemab (Kisunla): Traditional approval granted July 2, 2024.
• Aducanumab (Aduhelm): Accelerated approval 2021; voluntarily withdrawn by Biogen June 2024 after confirmatory trial cancellation and negligible uptake.
• Medicare coverage: Both drugs covered under Coverage with Evidence Development (CED), requiring participating clinicians to enroll patients in a CMS-approved registry.

• Lecanemab (Leqembi): MHRA marketing authorization granted December 2024. NICE published draft guidance in January 2025 recommending against NHS funding, citing insufficient clinical benefit relative to cost and ARIA monitoring burden. NICE issued final guidance on June 19, 2025 recommending against routine NHS use. As of June 2026, lecanemab is MHRA-approved but not funded by the NHS.
• Donanemab (Kisunla): MHRA approved May 2025. NICE's June 19, 2025 final guidance also recommends against routine NHS use of donanemab — both drugs were declined together.
• Practical implication: UK patients can access both drugs privately at approximately £25,000–30,000 per year, or through clinical trials.
• Named UK center: UCL Queen Square Institute of Neurology — Dementia Research Centre, Professor Nick Fox. Phone: +44 (0)20 3448 8777. National Hospital for Neurology and Neurosurgery, Queen Square, London.

• Lecanemab (Leqembi): EMA initially issued a negative opinion July 2024; following re-examination by Eisai, the EMA granted conditional marketing authorization January 2025 — with a restricted indication excluding APOE ε4 homozygotes and mandatory ARIA monitoring requirements.
• Donanemab (Kisunla): EMA marketing authorization granted May 2025, with similar ARIA monitoring requirements.
• Reimbursement: Decisions at national level. Germany (G-BA/IQWiG), France (HAS), and other national HTA bodies conducting independent evaluations. Coverage pending in most EU member states as of June 2026.
• Named EU center: DZNE (German Center for Neurodegenerative Diseases) — hubs in Munich, Bonn, Berlin, Tübingen. Website: dzne.de.
• Named EU center: Karolinska Institutet Memory Research Unit — Stockholm, Sweden. Home of the BioFINDER studies (Oskar Hansson, Henrik Zetterberg laboratories).

• Both hold EU marketing authorization applicable in France. HAS reimbursement assessment ongoing.
• Named French center: Hôpital de la Pitié-Salpêtrière (Paris) — Institut de Mémoire et de la Maladie d’Alzheimer (IM2A). Professor Stéphane Epelbaum leads clinical programs including lecanemab and donanemab evaluation. Part of AP-HP (Assistance Publique – Hôpitaux de Paris) network.
• CMRR network: France's national Mémoire, Ressources et Recherche centers provide specialist evaluation throughout French territory. Find yours via France Alzheimer.

• Lecanemab (Leqembi): Approved September 25, 2023 by Japan's PMDA — the first country outside the US to approve a traditional anti-amyloid therapy. Reimbursed by Japan's national insurance system (NHI) from December 2023.
• Donanemab (Kisunla): Approved in Japan September 2024.
• Named Japanese center: National Center for Geriatrics and Gerontology (NCGG) — Obu, Aichi. The flagship Japanese public research center for aging and Alzheimer's; leads J-ADNI.

• Lecanemab (Leqembi): Health Canada granted authorization in October 2025 (with conditions), restricted to APOE ε4 non-carriers or heterozygotes with confirmed amyloid pathology — the first disease-modifying Alzheimer's treatment approved in Canada. CADTH (CDA-AMC) reimbursement review and provincial formulary listing followed.
• Donanemab (Kisunla): Health Canada approved donanemab on May 1, 2026 — the second disease-modifying Alzheimer's treatment approved in Canada (similar APOE ε4 non-carrier/heterozygote-restricted indication).
• Named Canadian centers:
  • Baycrest Health Sciences — Toronto. Rotman Research Institute. Phone: 416-785-2500.
  • Sunnybrook Health Sciences Centre — Toronto. Hurvitz Brain Sciences Research Program. Phone: 416-480-4797.
  • McGill Centre for Studies in Aging (MCSA) — Montreal. Phone: 514-340-8222.

• Australia (TGA): The TGA approved donanemab (Kisunla) in May 2025 and lecanemab (Leqembi) in September 2025 (the latter after an initial 2024 rejection and reconsideration), both restricted to APOE ε4 non-carriers or heterozygotes. PBAC assessment will determine any subsidized access; access otherwise out-of-pocket. Australian academic sites include NeuRA, Austin Health, and Royal Melbourne Hospital.
• South Korea: MFDS approved lecanemab 2024. Reimbursement under HIRA consideration.
• China: NMPA approved lecanemab January 2024. APOE ε4 frequency is lower in Han Chinese populations.
• Israel: Israeli Ministry of Health approved lecanemab. Reimbursement through the national health basket under consideration. Named center: Tel Aviv Sourasky Medical Center (Ichilov) — Memory Clinic, Neurological Institute.

• Drug: Aducanumab (Aduhelm), Biogen
• Timeline: Accelerated FDA approval granted June 7, 2021 — one of the most controversial FDA decisions in recent memory. The agency overruled its own advisory committee, which had voted overwhelmingly against approval. Three advisory committee members resigned in protest.
• The controversy: Two Phase 3 trials (EMERGE and ENGAGE) were halted in 2019 for futility. After additional data analysis, Biogen and the FDA concluded EMERGE showed a statistically significant clinical benefit, but ENGAGE did not.
• Withdrawal: Biogen voluntarily withdrew aducanumab from the US market; announced June 2024. The confirmatory trial required by accelerated approval was cancelled. At its peak listed price of $56,000/year, uptake was minimal. As of June 2024, Aduhelm is no longer commercially available in any country.

• Drug: Gantenerumab (Roche/AC Immune)
• Trials: GRADUATE I and GRADUATE II — two Phase 3 trials in early Alzheimer's. Results reported November 2022.
• Result: Both trials failed to show a statistically significant effect on CDR-SB at 116 weeks, despite reducing amyloid burden on PET. Amyloid removal alone does not guarantee clinical benefit.
• Current status: Roche discontinued gantenerumab development in late 2022.

• Drug: Solanezumab (Eli Lilly) — targeted soluble (not plaque-bound) amyloid monomers
• EXPEDITION3 (2016): Phase 3 trial in mild Alzheimer's dementia. 2,129 patients. Failed primary endpoint. PMID: 29365294.
• PREVENT-AD (2023): Phase 3 trial in cognitively normal older adults with first-degree relatives with Alzheimer's. 1,169 participants. Failed — solanezumab did not delay cognitive decline vs. placebo over 4.5 years.
• Legacy: PREVENT-AD's failure was a landmark because it targeted the earliest possible intervention window and still failed. Treating people without confirmed amyloid pathology was the likely key flaw — now addressed by mandatory biomarker confirmation in all major trials.

• Drug: ALZ-801 (valiltramiprosate), an oral pill designed to block toxic amyloid clumps (oligomers), tested specifically in people who carry two copies of the APOE4 gene (the highest-genetic-risk group).
• APOLLOE4 (2025): The Phase 3 trial (NCT04770220) did not meet its main cognitive goal (ADAS-Cog13). Some pre-specified subgroup and brain-imaging signals were reported, but the trial did not show a clear cognitive benefit.
• Status: Not approved. An oral, infusion-free anti-amyloid pill remains an attractive idea, but this trial did not establish that ALZ-801 works.

• Drug: Bapineuzumab (Pfizer/Johnson & Johnson) — one of the first anti-amyloid mAbs in Phase 3
• Result: Four Phase 3 trials all failed to show clinical benefit. Program discontinued August 2012. ARIA was observed even at this early stage, foreshadowing the monitoring challenges that would dominate subsequent programs.
• Significance: Losses exceeded $2.5 billion. Led many to question the amyloid hypothesis — until the later success of lecanemab and donanemab validated the approach with better-designed trials in earlier populations.

• Verubecestat (MK-8931, Merck): EPOCH trial (Phase 2/3 in mild-to-moderate AD) stopped February 2017 because patients receiving verubecestat were doing worse than placebo — cognitive scores declined faster on the drug (PMID: 29432330). APECS trial (prodromal AD) also stopped February 2018 for futility and possible harm.
• Atabecestat (JNJ-54861911, Janssen): Phase 2b/3 prevention trial stopped April 2018 due to liver enzyme elevations (hepatotoxicity) and signs of accelerated cognitive decline in the treated group.
• Mechanism of harm: BACE1 has multiple biological substrates beyond APP. The enzyme is involved in myelination, synaptic plasticity, and neuregulin processing. Prolonged BACE inhibition disrupts synaptic function independent of amyloid reduction.
• Class outcome: All BACE inhibitors in late-stage development (verubecestat, atabecestat, lanabecestat, umibecestat, elenbecestat) have failed due to either lack of efficacy, cognitive worsening, or toxicity. The BACE inhibitor class is effectively abandoned for Alzheimer's treatment.

• Drug: Semagacestat (LY450139), Eli Lilly
• Result: Phase 3 IDENTITY trial stopped August 2010. Patients had significantly worse cognitive and functional outcomes than placebo, plus increased rates of skin cancer (PMID: 23883379).
• Mechanism of harm: Gamma-secretase cleaves Notch, a developmentally critical signaling protein. Blocking Notch processing disrupts multiple biological pathways essential to normal cell function throughout the body.
• Class outcome: All gamma-secretase inhibitors for Alzheimer's have been abandoned.

• Ginkgo biloba: The GEM trial (3,069 elderly adults, 6.1 years) showed ginkgo did not reduce dementia incidence vs. placebo (PMID 19017911). Not recommended.
• High-dose vitamin E: No dementia prevention benefit in large trials. High-dose vitamin E (≥400 IU) associated with increased all-cause mortality in meta-analyses. Not recommended.
• Statins: LEADe (atorvastatin) and HPS-MIND (simvastatin) trials found no cognitive benefit in established Alzheimer's. Ongoing observational interest; not established as Alzheimer's prevention.
• Omega-3 fatty acids: Multiple trials (OMEGA-AD, OMIC) found no benefit on cognitive decline. Remain healthful for cardiovascular reasons; not an Alzheimer's treatment.
• Turmeric/curcumin: No well-powered human RCT has demonstrated clinical benefit. Bioavailability is a major challenge. Not recommended.
• Coconut oil / medium-chain triglycerides: No randomized clinical trial data support use. The ketone body theory has not translated to clinical benefit in trials. Not recommended.
• NSAIDs: ADAPT trial (naproxen and celecoxib) stopped early due to cardiovascular safety concerns; naproxen showed a non-significant trend toward increased cognitive decline (PMID 17431236). Not recommended for Alzheimer's prevention.
• Hormone replacement therapy: WHIMS found that conjugated estrogens ± progestin increased the risk of dementia in women ≥65 (PMID 12771112). HRT is not recommended for dementia prevention.

The year after diagnosis is often the hardest emotionally and one of the most important practically. Key priorities:

• Process together, but at the person's pace. Allow time and space for grief. Grief is a normal response to loss — of a future you had imagined.
• Establish what the person wants while they can tell you. Preferences for future care, end-of-life wishes, values — these conversations are far easier now than later.
• Build the team now. Memory specialist, primary care, neuropsychologist, social worker, care manager, Alzheimer's Association contact, elder law attorney.

Legal documents — do this now, while you still can:

• Durable Power of Attorney for Finance (DPOA-F) — authorizes a trusted person to manage financial affairs when the principal becomes incapacitated. Durable means it remains valid after incapacity — a regular POA terminates at incapacity, exactly when you need it most.
• Durable Power of Attorney for Healthcare (DPOA-HC) / Healthcare Proxy — designates who can make medical decisions when the person can no longer do so themselves.
• Advance Directive / Living Will — documents specific preferences about life-sustaining treatment, resuscitation, artificial nutrition, mechanical ventilation. Download state-specific forms at CaringInfo.org.
• POLST (Portable Orders for Life-Sustaining Treatment) — a medical order (signed by a physician) that translates care preferences into actionable orders for emergency responders and hospital staff.
• Will and estate review — update beneficiaries on all accounts, insurance policies, and retirement funds.
• Long-term care planning — Medicare does not cover custodial memory care facility costs. Medicaid covers long-term care for people who have spent down to Medicaid-eligibility thresholds. An elder law attorney can advise — find one via naela.org.
• Veterans benefits — VA Aid and Attendance benefits may fund in-home or memory care costs. Call 1-800-827-1000.

• Savvy Caregiver Program — 6-week structured group education program. Evidence-based: reduces caregiver burden and depression. Available through Alzheimer's Association chapters and area agencies on aging.
• Teepa Snow — Positive Approach to Care — occupational therapist who developed a widely respected practical education program for dementia caregivers. Online and in-person courses. Website: teepasnow.com.
• REACH II (Resources for Enhancing Alzheimer's Caregiver Health) — Evidence-based intervention program delivered by trained social workers and care managers. Addresses caregiver depression, burden, and problem-solving skills.
• Alzheimer's Association Education Programs — Free online and in-person workshops on understanding the diagnosis, legal and financial planning, effective communication, home safety, and end-of-life planning. Access via alz.org or call 1-800-272-3900.
• ALZConnected — Alzheimer's Association online caregiver community. Moderated peer support forums available 24/7. alzconnected.org.

Research consistently shows that caregivers who use respite maintain better health, provide better care, and delay nursing-home placement. Options include:

• Adult day programs — structured daytime activities in a community setting. Social stimulation, structured routine, skilled supervision for the person with dementia; free time for the caregiver. Find programs via the Eldercare Locator (eldercare.acl.gov), or in Utah: Utah Department of Health and Human Services Aging and Adult Services (1-877-424-4640).
• In-home respite — trained care aides providing relief in the home. The National Respite Locator (archrespite.org) can find local providers.
• Short-term inpatient respite — 1–4 weeks in a memory care or skilled nursing facility. Medicare Part A covers up to 5 days of inpatient respite for hospice-enrolled patients.
• VA Caregiver Support Program — For veteran-patients, significant caregiver support including training, stipends, and respite. Call 1-855-260-3274.
• LIFESPAN Respite Care Program (federal program) — grants to states to fund caregiver respite. Access through your state's Area Agency on Aging.

• ADAS-Cog (Alzheimer's Disease Assessment Scale — Cognitive Subscale) — A standardized 11-item cognitive test used in clinical trials to measure severity of cognitive impairment. Higher scores indicate more impairment. Used as primary endpoint in many failed trials of the 2000s–2010s; more recent trials often use CDR-SB or iADRS because they are more sensitive to early-stage changes.
• APOE (Apolipoprotein E) — A gene with three common variants (ε2, ε3, ε4). The ε4 variant is the strongest known genetic risk factor for late-onset Alzheimer's. One ε4 allele increases lifetime risk approximately 3–4 times; two ε4 alleles (homozygous) increases risk approximately 8–12 times. APOE genotyping is now standard before starting anti-amyloid therapy because ε4/ε4 individuals have substantially higher ARIA risk.
• Amyloid PET — A brain imaging scan that uses radioactive tracers to detect amyloid plaques. A positive scan confirms amyloid pathology; a negative scan essentially rules out Alzheimer's as the cause of cognitive symptoms. Medicare now covers amyloid PET for qualifying patients with MCI or mild dementia.
• ARIA-E (Amyloid-Related Imaging Abnormality — Edema/Effusions) — Brain swelling or fluid accumulation detected on MRI, occurring as a side effect of anti-amyloid antibody therapy. Usually detected on surveillance MRI before causing symptoms. When symptomatic, can cause headache, confusion, visual changes, or dizziness. Usually resolves with drug pause.
• ARIA-H (Amyloid-Related Imaging Abnormality — Hemosiderin Deposits) — Microscopic bleeding (microhemorrhages) or surface bleeding (superficial siderosis) detected on MRI as a side effect of anti-amyloid antibody therapy. Often accompanies ARIA-E. Usually asymptomatic.
• Biomarker — A measurable biological indicator of disease. In Alzheimer's: amyloid beta (measured in blood, CSF, or PET), tau/phospho-tau (blood or CSF), neurodegeneration markers (neurofilament light chain / NfL, hippocampal volume on MRI). Biomarkers can indicate disease before symptoms appear.
• Blood-based biomarker — A biomarker measurable from a blood sample. The FDA-cleared May 2025 Lumipulse Plasma p-tau217/Aβ1-42 Ratio Test is the first blood test cleared to support Alzheimer's diagnosis. Accuracy for identifying Alzheimer's pathology: approximately 90%+ in clinically symptomatic populations in validation studies.
• CDR-SB (Clinical Dementia Rating — Sum of Boxes) — A composite clinical rating scale assessing cognition and function across 6 domains: memory, orientation, judgment, community affairs, home and hobbies, and personal care. Each domain rated 0–3; sum (0–18) is the CDR-SB. Primary endpoint in CLARITY-AD. Lecanemab produced a 0.45-point improvement on CDR-SB at 18 months.
• Cholinesterase inhibitor — A class of symptomatic medications (donepezil, rivastigmine, galantamine) that block the enzyme acetylcholinesterase, raising acetylcholine levels in the brain. Modestly improves cognition and behavior. Do not slow disease progression. Common side effects: nausea, diarrhea, vivid dreams, slowed heart rate.
• Cognitive reserve — The brain's resilience against cognitive decline despite pathological damage. People with higher education, intellectual engagement, bilingualism, and social activity tend to show symptoms of Alzheimer's later, even with similar pathological burden.
• CSF (Cerebrospinal Fluid) — The fluid surrounding the brain and spinal cord. A lumbar puncture (spinal tap) can sample CSF to measure amyloid beta and tau biomarkers with high accuracy. A standard confirmatory test before starting anti-amyloid therapy, especially where amyloid PET is unavailable.
• Dementia — A syndrome of cognitive decline severe enough to interfere with daily functioning and independence. It is not a disease itself — Alzheimer's is the most common cause (60–80%), but vascular dementia, Lewy body dementia, frontotemporal dementia, and mixed types are all important.
• Disease-modifying therapy (DMT) — A treatment that alters the underlying biology of the disease, not just symptoms. Lecanemab and donanemab are the first disease-modifying therapies approved for Alzheimer's, reducing brain amyloid. By contrast, cholinesterase inhibitors and memantine are symptomatic treatments.
• Donanemab (Kisunla) — An anti-amyloid monoclonal antibody (Eli Lilly) that received FDA traditional approval July 2024. Given by IV infusion every 4 weeks. Treatment can be stopped once amyloid is cleared on PET (more than half of patients achieve this by 12 months). Carries a black-box warning for ARIA; APOE genotyping required before starting.
• FAST (Functional Assessment Staging Test) — A 7-stage scale describing Alzheimer's disease progression in terms of functional abilities. FAST 7 (stages 7a–7f) describes severe dementia. Hospice eligibility for dementia often uses FAST stage 7c or beyond as one criterion.
• Hippocampus — A brain region critical for forming new memories. Atrophy (shrinkage) of the hippocampus on MRI is one of the earliest structural brain changes in Alzheimer's disease. Memory is affected early because of hippocampal involvement.
• Lecanemab (Leqembi) — An anti-amyloid monoclonal antibody (Eisai/Biogen) that received FDA traditional approval July 2023. Given as 10 mg/kg IV every 2 weeks (subcutaneous maintenance formulation FDA-approved August 2025). Approved in the US, Japan, UK (MHRA), EU (restricted label), Canada, and approximately 50 countries.
• MCI (Mild Cognitive Impairment) — A stage between normal aging and dementia where cognitive changes are measurable on testing but the person can still live independently. MCI due to Alzheimer's (confirmed by biomarkers) is the earliest symptomatic stage eligible for anti-amyloid therapy.
• Memantine (Namenda) — An NMDA receptor antagonist approved for moderate-to-severe Alzheimer's dementia. Modest symptomatic benefit. Often combined with a cholinesterase inhibitor. Does not slow disease progression. Available as immediate-release (target 10 mg twice daily) and extended-release Namenda XR (target 28 mg once daily).
• MMSE (Mini-Mental State Examination) — A widely used 30-point screening test for cognitive impairment. Scores ≥24 generally normal; 18–23 mild impairment; 10–17 moderate; <10 severe. Less sensitive to early/subtle impairment than the MoCA.
• MoCA (Montreal Cognitive Assessment) — A 30-point cognitive screening test more sensitive to mild impairment than the MMSE. Assesses visuospatial skills, executive function, naming, memory, attention, language, abstraction, and orientation. Scores ≥26 generally normal. Standard first-line brief cognitive screen in memory clinics.
• NFT (Neurofibrillary Tangle) — Abnormal accumulations of tau protein inside neurons. Along with amyloid plaques, NFTs are one of the two hallmarks of Alzheimer's pathology. NFT burden correlates more closely with cognitive decline than amyloid burden does.
• NIA-AA Criteria (2024) — The revised diagnostic and staging framework for Alzheimer's disease. Defines Alzheimer's biologically based on biomarker evidence of amyloid and tau pathology, independent of symptoms. Published in Nature Aging 2024; PMID 38934362.
• Neuropsychological testing — A comprehensive battery of standardized cognitive tests administered by a neuropsychologist, typically taking 3–6 hours. Measures memory, language, attention, executive function, visuospatial skills, and processing speed. Far more sensitive and specific than brief cognitive screens.
• pTau217 (phospho-tau 217) — A specific form of tau protein phosphorylated at position 217. Elevated pTau217 in blood or CSF is one of the most accurate biomarkers for distinguishing Alzheimer's from other causes of cognitive impairment. The FDA-cleared May 2025 Lumipulse blood test measures the ratio of pTau217 to amyloid beta 1-42.
• POLST (Portable Medical Orders for Life-Sustaining Treatment) — A medical order (signed by a physician) that specifies treatment preferences for resuscitation, hospitalization, and artificial nutrition. Unlike an advance directive (a legal document), POLST is an actual medical order that emergency responders and hospital staff can act on immediately. Also called MOLST, MOST, or DNAR depending on state.
• Synapse — The connection between neurons through which nerve signals pass. Alzheimer's disease causes progressive loss of synapses, which underlies cognitive and functional decline. Synaptic loss correlates most closely with cognitive impairment — which is why synaptic protection and repair is a key target for next-generation drug development.
• Tau — A protein that stabilizes the internal skeleton of neurons. In Alzheimer's, tau becomes abnormally phosphorylated, detaches from the neuron skeleton, aggregates into neurofibrillary tangles, and spreads through the brain in a characteristic staging pattern. Tau pathology correlates more closely with cognitive decline than amyloid does.
• Thickened liquids — A dietary modification used in advanced dementia when swallowing dysfunction (dysphagia) creates aspiration risk. Standardized by the IDDSI (International Dysphagia Diet Standardisation Initiative) seven-level framework. Prescribed by speech-language pathologists based on swallowing evaluation.
• ARIA monitoring protocol — The required MRI schedule during anti-amyloid therapy: baseline MRI before first infusion; for lecanemab, an added MRI between the 2nd and 3rd infusions (2025 FDA safety update) plus before the 5th, 7th, and 14th doses; infusion 2 and 4 MRIs for donanemab; symptom-triggered MRIs for any new neurological symptoms. APOE ε4/ε4 patients require more frequent imaging.