How do Lewy‑body dementia and frontotemporal dementia differ in age of onset, clinical presentation, imaging findings, and treatment?

Lewy Body Dementia vs Frontotemporal Dementia: Clinical Features, Imaging, and Treatment

Age of Onset

Frontotemporal dementia typically presents earlier than Lewy body dementia, with FTD being rare after age 75, while DLB is most common in older adults and constitutes up to 15% of dementia cases in the elderly. 1

• FTD: Unlike Alzheimer's disease which increases with age, FTD is uncommon after 75 years 1
• DLB: Second most common neurodegenerative dementia in elderly populations, with prevalence of 15% in those >68 years 1, 2

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Clinical Presentation

Lewy Body Dementia Core Features

The diagnosis of DLB requires dementia plus at least two of four core clinical features: fluctuating cognition, recurrent visual hallucinations, spontaneous parkinsonism, and REM sleep behavior disorder. 3, 4

Core clinical features include:

• Fluctuating cognition: Pronounced variations in attention, alertness, and cognitive function occurring over minutes to days 3, 4
• Recurrent visual hallucinations: Well-formed, detailed hallucinations typically involving people, animals, or objects 3, 4
• Spontaneous parkinsonism: Bradykinesia, rigidity, tremor, and postural instability without prior neuroleptic exposure 3, 4
• REM sleep behavior disorder: Acting out dreams due to lack of normal muscle paralysis during REM sleep, often preceding cognitive symptoms by years 3, 4

Supportive features:

• Autonomic dysfunction (orthostatic hypotension, urinary incontinence, constipation) 3
• Transient episodes of unresponsiveness related to attention fluctuations 3
• Severe neuroleptic sensitivity to traditional antipsychotics 3, 5

Cognitive profile:

• Executive dysfunction, attention deficits, and visuospatial impairment are prominent 3
• Memory is relatively preserved compared to Alzheimer's disease 6

Frontotemporal Dementia Core Features

FTD presents with early prominent behavioral and personality changes or language deficits, without the fluctuating cognition, visual hallucinations, or parkinsonism characteristic of DLB. 1

Behavioral variant FTD (bvFTD) features:

• Personality changes and behavioral disturbances as primary manifestations 1
• Severe social cognition impairment, more pronounced than in psychiatric disorders 1
• Disinhibition, apathy, loss of empathy, and compulsive behaviors 1
• Impaired emotion recognition on tasks like the Ekman 60 Faces Test 1

Language variants (Primary Progressive Aphasia):

• Semantic variant PPA: Loss of word meaning and object knowledge 6
• Nonfluent agrammatic PPA: Effortful speech with grammatical errors 6

Key differentiating point: Early prominent behavioral changes, personality alterations, or language deficits are typical of FTD but are NOT core features of DLB 4

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Imaging Findings

Structural Imaging (MRI)

Brain MRI without contrast is the first-line imaging test for both conditions to exclude structural mimics and assess characteristic atrophy patterns. 1, 4

Lewy Body Dementia:

• Relative preservation of medial temporal lobe structures and hippocampi compared to Alzheimer's disease 1, 4, 6
• Loss of the "swallow-tail sign" on susceptibility-weighted imaging (SWI), similar to Parkinson's disease 1, 4
• Less pronounced volume loss overall compared to AD 1, 6

Frontotemporal Dementia:

• Pathological atrophy in frontal or anterior temporal areas increases diagnostic certainty from "possible" to "probable" FTD (specificity increases from 82% to 95%) 1
• Atrophy patterns vary by subtype: frontal predominance in bvFTD, anterior temporal in semantic variant PPA 1
• Visual rating scales (global cortical atrophy, Kipps scale) can assess atrophy severity 1
• Volumetric MRI techniques (voxel-based morphometry, cortical thickness) may detect subtle early atrophy 1

Functional Imaging (FDG-PET)

FDG-PET is an established tool for differentiating DLB from FTD and has high diagnostic accuracy. 1

Lewy Body Dementia:

• Occipital lobe hypometabolism is a distinguishing feature of DLB 1, 4, 6
• "Cingulate island sign": Preserved FDG uptake in posterior cingulate gyrus despite occipital hypometabolism, highly specific for DLB over AD 1, 4
• Decreased metabolism in temporal, parietal, and occipital lobes plus cerebellum 1

Frontotemporal Dementia:

• Bilateral frontal and/or anterior temporal hypometabolism 1
• FDG-PET has 60% sensitivity and 78.5% positive predictive value for differentiating FTD from AD 1
• Hypometabolism patterns often precede visible atrophy on structural MRI 1

Dopamine Transporter Imaging (DaTscan)

DaTscan (I-123 Ioflupane SPECT) is a supportive biomarker with approximately 78% sensitivity and 90% specificity for DLB. 1, 4

Lewy Body Dementia:

• Reduced striatal dopamine transporter uptake with loss of normal comma-shaped appearance in putamina 1, 4
• Abnormal in both DLB and Parkinson's disease dementia 4

Frontotemporal Dementia:

• Normal dopamine transporter uptake (not indicated for FTD evaluation) 4

Perfusion SPECT

Frontotemporal Dementia:

• Bilateral anterior brain hypoperfusion on Tc-99m HMPAO SPECT distinguishes FTD from AD and vascular dementia 1
• May be used as adjunct but not first-line test 1

Amyloid PET

Amyloid PET should NOT be used to differentiate DLB from FTD, as co-existent amyloid pathology is common in DLB (up to 63% in those >80 years). 1, 4

• In FTD, amyloid PET is limited to excluding underlying AD pathology in atypical presentations 1
• The Society of Nuclear Medicine states amyloid PET is rarely appropriate in suspected DLB 1

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Treatment

Lewy Body Dementia Treatment

Cholinesterase inhibitors are first-line treatment for both cognitive symptoms and visual hallucinations in DLB, with rivastigmine and donepezil being the primary agents. 3, 5

Pharmacologic management:

• Cholinesterase inhibitors (rivastigmine, donepezil): First-line for cognition and hallucinations 3, 5
• Levodopa: Use cautiously for motor symptoms, as dopaminergic agents risk inducing or worsening psychotic symptoms 3
• ABSOLUTE CONTRAINDICATION: Traditional antipsychotics must be avoided due to severe neuroleptic sensitivity that significantly increases morbidity and mortality 3, 5

Non-pharmacologic management:

• Education and reassurance for patients and caregivers 5
• Management of autonomic dysfunction (orthostatic hypotension, constipation) 3

Frontotemporal Dementia Treatment

There are no FDA-approved disease-modifying treatments for FTD; management is primarily symptomatic and supportive. 1

Current approach:

• No cholinesterase inhibitors or memantine have demonstrated efficacy in FTD 1
• Behavioral management strategies and caregiver education are primary interventions 1
• Selective serotonin reuptake inhibitors (SSRIs) may help with behavioral symptoms, though evidence is limited 1
• Avoid antipsychotics when possible due to limited efficacy and side effect risks 1

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Critical Diagnostic Pitfalls

Common pitfalls to avoid:

1. Do not diagnose AD when core DLB features are present, even if amyloid biomarkers are positive – clinical phenotype takes precedence 3, 4, 5

2. Recognize that mixed pathology is extremely common: Over 50% of DLB cases have coexistent AD pathology 3, 4

3. The "1-year rule" differentiates DLB from Parkinson's disease dementia: If cognitive impairment appears before or within 1 year of motor symptoms, diagnose DLB; if dementia develops after ≥1 year of established Parkinson's motor symptoms, diagnose PDD 4

4. Early visual hallucinations strongly favor DLB over FTD or AD – this is not a core feature of either FTD or AD 3, 4

5. Absence of stroke history or stepwise decline makes primary vascular dementia unlikely when DLB or FTD phenotype is present 4

6. Structural imaging alone may be insufficient in early FTD – sensitivity is only 70%, particularly in genetic cases 1