Key Facts

DLB is frequently underdiagnosed or misdiagnosed as AD or Parkinson disease. Recognition is essential because of the severe antipsychotic sensitivity and good response to cholinesterase inhibitors. RBD may precede dementia by years.

Epidemiology

Prevalence: ~10-15% of all dementia. M:F 1.5:1. Mean onset 65-80 years. Likely underdiagnosed (some estimates suggest up to 20% of dementia may be DLB).

Aetiology

• Alpha-synuclein pathology: Lewy bodies (intraneuronal α-synuclein inclusions) in cortical and subcortical neurones
• Same protein as Parkinson disease — DLB and PDD exist on a spectrum ('Lewy body diseases')
• Concomitant AD pathology (amyloid plaques) common (~50%)
• Genetic: GBA mutations (glucocerebrosidase) — strongest genetic risk factor for DLB (same as PD); APOE ε4

Pathophysiology

Widespread cortical and subcortical Lewy body deposition → neuronal dysfunction and death. Cortical Lewy bodies → fluctuating cognition, hallucinations, visuospatial dysfunction. Substantia nigra → parkinsonism. Brainstem (pedunculopontine nucleus) → RBD. Cholinergic deficit is MORE SEVERE than in AD (greater loss of nucleus basalis neurones) → explains good response to ChEIs and prominent visual hallucinations.

Core Features (2 = probable DLB; 1 = possible DLB)

• Fluctuating cognition: pronounced variations in attention and alertness; episodes of staring, confusion, drowsiness alternating with lucid intervals; may mimic delirium
• Recurrent visual hallucinations: detailed, well-formed (people, children, animals); often not distressing initially; patient may have insight
• REM sleep behaviour disorder: acting out dreams (hitting, kicking, shouting during sleep); may precede cognitive symptoms by years
• Spontaneous parkinsonism: rigidity, bradykinesia > rest tremor (tremor less prominent than in PD)

Supportive Features

• Repeated falls, syncope, transient loss of consciousness
• Severe autonomic dysfunction (orthostatic hypotension, constipation, urinary incontinence)
• Hypersomnia, depression, anxiety
• Hyposmia
• Systematised delusions (often paranoid)

Red Flags

• Antipsychotic prescription in suspected DLB: EXTREME neuroleptic sensitivity — can precipitate severe rigidity, immobility, impaired consciousness, NMS-like picture
• Recurrent unexplained falls + cognitive fluctuations → consider DLB
• Visual hallucinations in a patient with mild parkinsonism → DLB not PD

Cognitive Assessment

• ACE-III, MoCA: fluctuating scores on serial testing is characteristic
• Visuospatial/constructional dysfunction prominent (clock drawing, intersecting pentagons)
• Attention testing: digit span, serial 7s (may fluctuate markedly)

Imaging

• MRI brain: relatively preserved medial temporal lobes/hippocampi (vs AD where atrophied); generalised cortical atrophy
• DaTSCAN (FP-CIT SPECT): reduced dopamine transporter uptake in basal ganglia — INDICATIVE biomarker (also abnormal in PDD; normal in AD); NICE recommended
• FDG-PET: occipital hypometabolism (cingulate island sign) — specific for DLB

Sleep Studies

• Polysomnography: REM sleep without atonia confirms RBD — indicative biomarker

Other

• Cardiac MIBG scintigraphy: reduced uptake (sympathetic cardiac denervation) — indicative biomarker; less widely available in UK
• EEG: prominent posterior slow-wave activity with periodic fluctuations
• CSF: AD biomarkers may be present (mixed pathology); α-synuclein RT-QuIC emerging

Bloods

• Standard dementia screen: FBC, U&Es, TFTs, B12/folate, calcium, glucose, LFTs

Pharmacological

Cognitive/Neuropsychiatric:

• Cholinesterase inhibitors: first-line — rivastigmine (preferred — also licensed for PDD; NICE TA217); donepezil, galantamine also effective
• Particularly effective for hallucinations, cognitive fluctuations, and attention
• Memantine 10-20mg OD: moderate-severe DLB; can be combined with ChEI

Parkinsonism:

• Levodopa (co-careldopa/co-beneldopa): can be used cautiously for motor symptoms; lower doses than PD; may worsen hallucinations
• Avoid dopamine agonists (worsen hallucinations/psychosis)

RBD:

• Clonazepam 0.25-2mg ON: first-line for RBD
• Melatonin 2-6mg ON: alternative/adjunct
• Bed safety measures (padded bed rails, mattress on floor)

Neuropsychiatric Symptoms:

• AVOID ANTIPSYCHOTICS — severe neuroleptic sensitivity (risk of NMS, irreversible parkinsonism, death)
• If antipsychotic absolutely essential (severe psychosis/risk): quetiapine at lowest possible dose for shortest duration
• NEVER use haloperidol, chlorpromazine, or risperidone in DLB

Autonomic:

• Orthostatic hypotension: fludrocortisone, midodrine, compression stockings
• Constipation: macrogol

Non-Pharmacological

• Carer education (especially re: antipsychotic risks, fluctuations, visual hallucinations)
• Occupational therapy, physiotherapy (falls prevention)
• Sleep hygiene for RBD
• Cognitive stimulation

Referral Criteria

• Specialist memory service/movement disorder clinic
• DaTSCAN: if diagnostic uncertainty between DLB and AD
• Sleep medicine: if RBD assessment needed

Mean survival from diagnosis ~6-8 years (slightly shorter than AD). More rapid cognitive decline than AD in some studies. Hallucinations and motor symptoms increase care burden. Falls are a major source of morbidity. Neuroleptic sensitivity is potentially fatal — must be communicated to all healthcare providers. Good response to ChEIs may provide significant benefit for hallucinations and cognitive fluctuations. RBD may precede DLB by 10-15 years (prodromal marker).

DLB vs PDD ('1-Year Rule')

McKeith Criteria for DLB (2017)