384.4 📋 章末速蚘 Summary

384.4.1 🔑 䞀句話瞜結

Dementia with Lewy bodies (DLB) = 3rd most common dementia (after AD and vascular); synucleinopathy; mean onset 50-85 + survival 5-8 years; 4 core clinical features: (1) fluctuating cognition (alertness, attention — sometimes lucid, sometimes severely impaired), (2) visual hallucinations (well-formed people/animals, recurrent, often non-threatening), (3) REM behavior disorder (RBD — acting out dreams, often prodromal), (4) parkinsonism (bradykinesia, rigidity, postural instability; tremor less prominent); supportive features — severe sensitivity to antipsychotics (can be life-threatening EPS/NMS-like — up to 50% have severe reaction) + autonomic dysfunction (orthostatic hypotension, urinary, constipation) + hypersomnia + non-visual hallucinations + apathy + anxiety + depression + delusions + repeated falls + syncope; DLB vs PD dementia (PDD) both synucleinopathies same pathology, distinguished by TIMING — DLB cognitive impairment within 1 year of OR before parkinsonism; PDD motor symptoms > 1 year before cognitive impairment; both treated similarly; pathology α-synuclein Lewy bodies cortical + diffuse (more than PD) + often co-exists with AD pathology (Aβ plaques); diagnosis McKeith 2017 criteria — probable DLB (dementia + ≥ 2 core) or possible DLB (dementia + 1 core + ≥ 1 indicative biomarker); indicative biomarkers — DaT-SCAN abnormal (reduced dopamine transporter) + MIBG cardiac scintigraphy decreased (vs preserved in MSA/AD) + polysomnography confirms RBD; supportive biomarkers — relative preservation of medial temporal lobe on MRI + generalized low uptake on FDG-PET especially occipital (distinguishes from AD) + cingulate island sign (preserved posterior cingulate on FDG-PET); treatment cognitive — cholinesterase inhibitors MORE RESPONSIVE than in AD — rivastigmine + donepezil; memantine modest; visual hallucinations — often tolerable if non-distressing + pimavanserin (Nuplazid) selective 5HT-2A inverse agonist FDA-approved for PD psychosis (off-label DLB) + low-dose quetiapine or clozapine if needed + AVOID typical antipsychotics + olanzapine + risperidone (severe sensitivity!); parkinsonism — levodopa cautiously (may worsen hallucinations) — lower doses; RBD — melatonin 3-12 mg HS + clonazepam 0.25-1 mg HS + safety measures; autonomic — midodrine + fludrocortisone + droxidopa for orthostatic + avoid anticholinergics + fiber/laxatives constipation; vascular cognitive impairment (VCI) = spectrum from VaMCI to vascular dementia (VaD); subtypes — multi-infarct dementia (multiple strokes, stepwise) + strategic infarct dementia (key locations: thalamus, angular gyrus) + subcortical ischemic vascular dementia (SIVD — small vessel disease, gradual) + hemorrhagic dementia (CAA, hypertensive bleeds) + mixed AD-vascular VERY COMMON; subcortical pattern features — psychomotor slowing + executive dysfunction + gait disorder + emotional lability + pseudobulbar + focal neurological signs; diagnosis cognitive impairment + vascular brain lesions on imaging + temporal/anatomic relationship + often coexists with AD; NO specific DMT — aggressive vascular risk factor management (BP control most important!) + statins + diabetes + smoking + diet + exercise + antiplatelet non-cardioembolic stroke prevention + anticoagulation for AF + carotid intervention if indicated; important entities — CADASIL (AD, NOTCH3 mutation — recurrent strokes + migraine + cognitive + mood + anterior temporal white matter) + CARASIL (AR, HTRA1, Asian) + Fabry disease (α-galactosidase) + Binswanger disease (subcortical small vessel + HTN + executive + gait) + NPH (normal pressure hydrocephalus — triad gait + cognitive + urinary incontinence “wet, wobbly, wacky”, ventricular enlargement, improvement with LP/VP shunt) + hippocampal sclerosis of aging (mimics AD, older patients, often + TDP-43 LATE) + mixed dementia AD + vascular common (30-40%)。

384.4.2 💊 治療粟芁

  • DLB cognitivecholinesterase inhibitors more responsive than in AD — rivastigmine 1.5-6 mg BID PO or 4.6-13.3 mg/24 hr patch + donepezil 5-23 mg/d; memantine 5-20 mg/d modest benefit
  • DLB psychosis (visual hallucinations + delusions)only if distressing; pimavanserin (Nuplazid) 34 mg/d selective 5HT-2A inverse agonist FDA-approved for PD psychosis (off-label DLB, HARMONY trial) + low-dose quetiapine 12.5-75 mg HS or clozapine 12.5-50 mg HS (monitor WBC) — AVOID typical antipsychotics + olanzapine + risperidone (severe sensitivity can be FATAL!)
  • DLB parkinsonismlevodopa LOW doses cautiously (may worsen hallucinations); avoid dopamine agonists (worse hallucinations)
  • DLB REM behavior disordermelatonin 3-12 mg HS preferred (less side effects) or clonazepam 0.25-1 mg HS + safety measures (clear bedroom + partner separate bed if needed)
  • DLB orthostatic hypotensionmidodrine 5-10 mg TID + fludrocortisone 0.1-0.3 mg/d + droxidopa (Northera) + salt + fluid + compression
  • VCI vascular risk factor management (KEY)BP control most important (target < 130/80) + high-intensity statin + diabetes A1c < 7% individualized + antiplatelet aspirin 81 mg/d for non-cardioembolic + DOAC for AF + carotid intervention if indicated + smoking cessation + diet + exercise + Mediterranean diet
  • VCI cognitive symptomaticcholinesterase inhibitors limited evidence (modest benefit in some); memantine modest; not standard
  • mixed AD-vasculartreat both — anti-amyloid mAbs (if AD predominant + early stage) + ChEI/memantine + vascular risk factors
  • NPHlarge-volume LP (tap test) + improvement → consider VP shunt; ICP monitoring select; programmable shunt

384.4.3 🎯 盧醫垫的考前提醒

  1. DLB 4 core features (memorize): (1) fluctuating cognition + (2) visual hallucinations (well-formed) + (3) REM behavior disorder + (4) parkinsonism; supportive — SEVERE antipsychotic sensitivity (life-threatening!) + autonomic + falls + syncope
  2. DLB vs PD dementia (PDD): timing distinction — DLB cognitive within 1 year of (or before) parkinsonism; PDD motor > 1 year before cognitive (same pathology, same treatment)
  3. DLB biomarkers: DaT-SCAN abnormal (reduced dopamine transporter) + MIBG cardiac scintigraphy decreased + polysomnography confirms RBD (indicative); cingulate island sign on FDG-PET + occipital hypometabolism + relative preservation of medial temporal lobe (supportive)
  4. DLB treatment: cholinesterase inhibitors (rivastigmine, donepezil) MORE RESPONSIVE than in AD + pimavanserin (Nuplazid) FDA-approved PD psychosis for hallucinations; AVOID typical antipsychotics + olanzapine + risperidone (severe sensitivity, up to 50% with severe EPS/NMS-like reactions — can be FATAL!) — use low-dose quetiapine or clozapine if needed
  5. DLB RBD treatment: melatonin 3-12 mg HS preferred (less side effects) or clonazepam 0.25-1 mg HS + safety measures
  6. DLB parkinsonism: levodopa LOW DOSES CAUTIOUSLY (may worsen hallucinations); AVOID dopamine agonists (worse hallucinations)
  7. Vascular cognitive impairment (VCI) subtypes: multi-infarct (stepwise) + strategic infarct (thalamus, angular gyrus) + subcortical ischemic SIVD (small vessel, gradual) + hemorrhagic (CAA) + mixed AD-vascular very common (30-40%)
  8. VCI subcortical pattern: psychomotor slowing + executive dysfunction + gait disorder + emotional lability + pseudobulbar + focal neurological signs
  9. VCI treatment: aggressive vascular risk factor management (BP < 130/80 most important + statin + DM + antiplatelet + smoking + diet + exercise); no specific DMT; ChEI limited evidence
  10. Important entities to distinguish: CADASIL (AD, NOTCH3, anterior temporal white matter + migraine + strokes + cognitive) + NPH (wet, wobbly, wacky → LP tap test → VP shunt) + Binswanger (subcortical small vessel + HTN) + hippocampal sclerosis of aging (mimics AD, often + TDP-43 LATE) + mixed dementia (AD + vascular) very common (30-40%)