Dementia Bouw

What are the 4 key distinguishing features of Alzheimer's disease dementia?

Insidious onset with gradual progression. Primary symptom is memory loss. Pathology: amyloid plaques and neurofibrillary tangles. Risk factors: APOE-e4 allele, presenilin mutations, age.

What are the 4 key distinguishing features of Vascular dementia?

Abrupt onset following a stroke or vascular event. Stepwise (staircase) deterioration — worsens with each new vascular event. Prominent executive dysfunction. Associated with gait changes, history of strokes or bleeding.

What are the 4 key distinguishing features of Lewy Body dementia?

Related to Parkinson's disease (alpha-synuclein deposits in the cortex). Prominent visual hallucinations. Sleep disorders (REM sleep behavior disorder). Motor symptoms (Parkinsonism). Critically: these patients are extremely sensitive to EPS from antipsychotics — even low-D2 agents can cause severe reactions.

What are the 4 key distinguishing features of Frontotemporal dementia?

Earlier onset — age 45–60. Personality and behavior changes are the dominant presentation (not memory early on). Language symptoms (aphasia). Pathology: atrophied neurons and "spongy" cortex. Memory is relatively preserved early.

How does the onset pattern differ across the 4 dementia types?

Alzheimer's: insidious, gradual. Vascular: abrupt, stepwise. Lewy Body: gradual with prominent hallucinations and motor symptoms. Frontotemporal: early personality/behavior changes, younger age of onset.

What MMSE score range corresponds to Mild dementia?

20–23 (out of 30). Time to onset from MCI: 1–3 years.

What MMSE score range corresponds to Moderate dementia?

11–19. Time to onset: 2–8 years from mild stage.

What MMSE score range corresponds to Severe dementia?

≤10. Time to onset: 6–12 years from moderate stage.

What MMSE score corresponds to MCI (Mild Cognitive Impairment)?

MMSE is N/A for MCI — the MMSE is a staging tool for diagnosed dementia, not for MCI. MCI is a preclinical stage (CDR 0.5, FAST 3).

What is the purpose of the MMSE vs. the MoCA/Mini-Cog?

MMSE = staging tool (tracks disease progression and medication effectiveness). MoCA and Mini-Cog = screening tools only (refer for further testing — do NOT diagnose or stage dementia). MMSE range: 0–30.

Which cholinesterase inhibitors (ChEIs) are approved and for which stages of AD?

Donepezil (Aricept): mild through severe. Galantamine (Razadyne) and benzgalantamine (Zunveyl): mild to moderate only. Rivastigmine ORAL (Exelon): mild to moderate. Rivastigmine PATCH: mild through severe. Rivastigmine patch has a broader indication than the oral form.

What is the mechanism of action of ChEIs and why are they used in AD?

Inhibit acetylcholinesterase → increase synaptic acetylcholine. Used because AD causes progressive loss of cholinergic neurons, reducing ACh availability. Provide symptomatic benefit only — do not slow disease progression.

Which drug classes have opposing MOA to ChEIs and should be avoided or used cautiously?

Anticholinergics (direct pharmacodynamic antagonism). Also watch for: cardiac drugs causing bradycardia or QT prolongation, and anticoagulants/antiplatelets (ChEIs increase bleeding risk).

What are the common adverse effects of ChEIs and how can they be managed?

GI: nausea (3–19%), diarrhea (5–15%) — slow dose escalation, take with food. CV: bradycardia, dizziness, syncope, QT prolongation. CNS: insomnia (2–14%), nightmares (3%), agitation — administer at night for sleep side effects, or switch to morning if agitation occurs. Consider rivastigmine patch (lower peaks) or benzgalantamine to reduce GI side effects.

What is memantine's mechanism of action and approved stage of use in AD?

NMDA receptor antagonist — blocks excess glutamate activity which is toxic to neurons. Approved for moderate to severe AD only (MMSE ≤19). NOT approved for mild AD or MCI.

What are the adverse effects and drug interactions of memantine?

ADEs: dizziness (5–7%), confusion (6%), headache (6%), anxiety (4%), constipation, diarrhea, hypertension. DDIs: dextromethorphan, amantadine (both NMDA antagonists — additive toxicity), carbonic anhydrase inhibitors. Disease interaction: conditions that alkalinize urine (severe UTI, high-protein diet) decrease memantine elimination.

What is Namzaric and when can it be used?

Namzaric is a fixed-dose combination of donepezil 10 mg + memantine ER (available in 7, 14, 21, 28 mg strengths). Patient must be stable on donepezil 10 mg daily before switching to Namzaric.

What is the treatment algorithm for initiating therapy by AD severity stage?

MCI: anti-amyloid MAB only (if eligible). Mild: anti-amyloid MAB alone OR ChEI alone OR ChEI + anti-amyloid MAB. Note: anti-amyloid MABs are NOT used alone for initiation in moderate or severe disease. Moderate (initiation): ChEI alone OR memantine alone OR ChEI + memantine. Severe (initiation): memantine alone.

What is the treatment algorithm for CONTINUING therapy as AD progresses?

Mild → continuing: ChEI + anti-amyloid MAB. Moderate → continuing: ChEI + memantine. Severe → continuing: ChEI +/- memantine, OR discontinue (clinical judgment needed at end stage).

What are the anti-amyloid monoclonal antibodies for AD and their mechanism?

Lecanemab (Leqembi), donanemab (Kisunla), aducanumab (Aduhelm). MOA: bind to aggregated soluble and insoluble forms of beta-amyloid → promote clearance of amyloid plaques. Must confirm presence of beta-amyloid pathology (via PET or lumbar puncture) before initiating.

Who are the anti-amyloid MABs indicated for, and what are the key contraindications?

Indicated for: MCI or mild dementia with confirmed amyloid pathology. AVOID in: APOE e4 homozygotes (extreme ARIA risk), bleeding disorders, stroke/TIA within the past year, moderate-severe dementia, non-AD pathology, BMI

What is ARIA and why does it matter with anti-amyloid MABs?

ARIA = Amyloid-Related Imaging Abnormalities. ARIA-E (edema/effusion) and ARIA-H (microhemorrhages). Caused by rapid amyloid clearance from vessel walls. Can be asymptomatic or cause headache, confusion, dizziness, vision changes. MRI monitoring is required before specific infusions to detect ARIA.

What is BPSD and what is the first step in managing it?

Behavioral and Psychological Symptoms of Dementia — includes psychosis, agitation, depression, sleep disturbances. First step is ALWAYS non-pharmacologic interventions (structured routines, music therapy, sensory stimulation, caregiver training, environmental modification) before adding medications.

What medications are used for BPSD psychosis and agitation?

First: optimize ChEI and/or memantine (may help behavioral symptoms). If needed: antipsychotics — brexpiprazole (FDA approved for agitation in AD) or SGAs (quetiapine, clozapine). Bupropion/dextromethorphan (Auvelity) — FDA approved for agitation in dementia. Carbamazepine (off-label). Avoid chronic benzodiazepine use.

What is the boxed warning for antipsychotics in dementia?

"Patients with dementia-related behavioral disorders treated with antipsychotics are at an increased risk of death compared to placebo." Most deaths were cardiac (sudden death, heart failure) or infectious (pneumonia). Risk applies to both FGAs and SGAs.

Which antipsychotic is the only one FDA-approved for agitation in AD, and which are preferred for Lewy Body dementia psychosis?

FDA-approved for AD agitation: brexpiprazole (Rexulti). For Lewy Body dementia psychosis: quetiapine (preferred, low D2) or clozapine (most efficacious). AVOID all high-D2 antipsychotics in Lewy Body dementia — risk of severe, potentially fatal EPS reactions.

What is the antipsychotic management algorithm for BPSD psychosis/agitation?

Initiate 4-week trial at minimum effective dose → assess response. If adequate response: continue ≤4 months → attempt taper. If symptoms worsen/return on taper: return to last effective dose only if benefits > risks. If no response: taper/discontinue. If side effects: discontinue. After discontinuing: monitor monthly × 4 months.

What monitoring is required for antipsychotics used in BPSD?

Behavior log and NPI-Q (symptom assessment). AIMS (abnormal movements). Lipids, A1c, weight (metabolic monitoring). QT prolongation, sedation, gait/fall risk.

What medications are used for BPSD depression?

First-line: SSRIs or SNRIs (citalopram, sertraline, venlafaxine). Mirtazapine (also helps sleep and appetite). Bupropion/dextromethorphan (FDA approved for agitation in dementia — also has antidepressant activity). Non-pharmacologic: CBT, ECT. Avoid: stimulants (on AGS Beers criteria in elderly).

What are the key concerns with SSRIs/SNRIs in elderly patients with BPSD depression?

Increased fall risk. Hyponatremia (SIADH — common in elderly). QT prolongation. Bleeding risk (especially with anticoagulants or antiplatelet agents).

What makes bupropion/dextromethorphan (Auvelity) notable in dementia?

It is FDA-approved for both agitation associated with dementia AND depression. MOA: bupropion is DA/NE reuptake inhibitor; dextromethorphan is a sigma-1 agonist and NMDA antagonist. Key ADE to monitor: decreased seizure threshold. Also causes dizziness, nausea, hyponatremia.

What medications are used for BPSD sleep problems?

Melatonin (first-line, safest). Trazodone (sedating antidepressant). Mirtazapine (also helps depression/appetite). Suvorexant (DORA — preferred over BZD receptor agonists in elderly). Zolpidem or zaleplon (short-term only). Avoid chronic benzodiazepine use (fall risk, cognitive worsening, dependence).

Why should benzodiazepines be avoided chronically in dementia patients with BPSD?

Benzodiazepines cause excessive sedation, worsening cognitive impairment, increased fall risk, and paradoxical disinhibition in elderly/demented patients. They also cause physical dependence with withdrawal risk. Chronic use is on the AGS Beers Criteria as a drug to avoid in older adults.

What are the overall recommendations for the major alternative/complementary therapies in AD?

Estrogen (HRT): Do NOT recommend — WHIMS trial showed increased AD rates in women >65. NSAIDs/anti-inflammatories: Do NOT recommend — larger trials showed no benefit over placebo. Ginkgo biloba: Not effective. Huperzine A: Not effective and causes significant GI adverse effects. Statins: Not effective for treating AD (may have epidemiologic associations but prospective trials did not show cognitive benefit). Vitamin E: Consider only in patients with no CVD or diabetes risk factors — small benefit on ADL decline but increased all-cause mortality at doses >400 IU/day.

What distinguishes donepezil from the other ChEIs in terms of stage of use?

Donepezil (Aricept) is the ONLY ChEI approved for use across all stages of AD — mild, moderate, AND severe. All other ChEIs are limited to mild-moderate (galantamine, benzgalantamine, rivastigmine oral). Exception: rivastigmine PATCH is also approved mild through severe.

What is the role of the APOE e4 allele in both AD risk and treatment decisions?

Risk: APOE e4 heterozygotes have 2–3× increased AD risk; homozygotes have ~12× risk. Treatment: APOE e4 homozygotes are contraindicated from receiving anti-amyloid MABs due to dramatically higher ARIA risk.