Dementias

Dementia with Lewy bodies

🧠 Dementia with Lewy Bodies (DLB) is the second most common form of degenerative dementia after Alzheimer’s disease. It is clinically important because it combines cognitive decline with parkinsonism, vivid hallucinations, and sleep disturbance, and patients are uniquely sensitive to antipsychotics. Histologically, a Lewy neuritis in the CA2 region of the hippocampus may be a distinctive feature of DLB.

📖 About

• Progressive neurodegenerative disorder characterised by dementia plus parkinsonian features.
• Distinct from Parkinson’s disease dementia (PDD) mainly by timing: in DLB, cognitive impairment appears before or within 1 year of motor symptoms (“1-year rule”).
• Accounts for 10–15% of dementia cases; more common in older adults (70+).
• Response to L-dopa is often limited, and neuroleptic sensitivity is a diagnostic red flag.

🧬 Aetiology & Pathology

• Caused by abnormal deposition of alpha-synuclein (Lewy bodies) in cortical and subcortical neurons.
• Lewy bodies contain proteins such as ubiquitin, parkin, and α-synuclein.
• Often coexists with Alzheimer’s pathology (amyloid plaques and tau tangles) → “mixed dementia”.
• Disruption of dopaminergic and cholinergic neurotransmission explains both parkinsonism and cognitive/psychiatric symptoms.

🔎 Clinical Features (Core)

• Fluctuating cognition: Episodes of confusion, reduced attention, or staring spells, alternating with near-normal lucidity.
• Visual hallucinations: Typically well-formed, vivid, and detailed (e.g., people, animals, children).
• Parkinsonism: Symmetrical bradykinesia, rigidity, shuffling gait; tremor less prominent than in idiopathic PD.
• REM Sleep Behaviour Disorder (RBD): Acting out dreams due to loss of REM atonia; may precede dementia by years.

✨ Supportive Features

• Delusions (often paranoid or bizarre).
• Neuroleptic sensitivity: severe extrapyramidal worsening with standard antipsychotics.
• Autonomic dysfunction: orthostatic hypotension, constipation, urinary incontinence.
• Depression and apathy are common comorbidities.

🧪 Investigations

• Blood tests: FBC, U&E, LFT, TFT, B12, folate – exclude reversible causes of cognitive impairment.
• MRI/CT: Often non-specific; may show generalised atrophy but hippocampi are relatively spared compared to Alzheimer’s.
• DaTSCAN (dopamine transporter SPECT): Reduced uptake in basal ganglia supports a diagnosis of DLB vs Alzheimer’s. DaTSCAN can be used when diagnostic uncertainty remains. It shows reduced dopamine transporter uptake in the basal ganglia, supporting a diagnosis of DLB compared to Alzheimer’s, but it is not required if the clinical features are clear.
• Sleep study: Polysomnography can confirm REM sleep behaviour disorder.

📋 Differentials

• Idiopathic Parkinson’s Disease: Dementia appears later (>1 year after motor symptoms).
• Alzheimer’s Disease: Memory impairment earlier and more dominant; hallucinations/parkinsonism not core early features.
• Vascular Dementia: Stepwise decline with vascular risk factors; imaging shows infarcts or white matter changes.

💊 Management

• Cognitive symptoms & hallucinations: Cholinesterase inhibitors (e.g., rivastigmine, donepezil) are first-line and may also reduce hallucinations.
• Parkinsonism: L-dopa can be tried but usually with modest benefit; monitor for worsening hallucinations.
• Psychosis: Avoid typical antipsychotics; if needed, use low-dose quetiapine or clozapine under specialist supervision.
• REM Sleep Behaviour Disorder: Clonazepam or melatonin at night.
• Depression: SSRIs (e.g., sertraline, citalopram) are preferred.
• Supportive Care: Carer education, multidisciplinary input (neurology, psychiatry, geriatrics), occupational therapy, and social support.

📌 Key Clinical Pearls

• Always ask about visual hallucinations – they are a core differentiator from Alzheimer’s.
• Antipsychotic sensitivity can be life-threatening (rigidity, neuroleptic malignant-like syndrome).
• Look for RBD – it can be an early marker of alpha-synucleinopathies (DLB, Parkinson’s, MSA).
• Cognitive fluctuations are often mistaken for delirium – careful history is essential.

📚 References

• NICE NG97: Dementia: assessment, management and support
• Alzheimer’s Society – Dementia with Lewy Bodies
• McKeith IG et al. Diagnosis and management of DLB, Lancet Neurology 2017

Frontotemporal dementia

🧠 Pick’s Disease (a form of Frontotemporal Dementia, FTD) is a rare neurodegenerative disorder. Some cases show intracytoplasmic tau-positive inclusion bodies, making it a type of tauopathy (also seen in Alzheimer’s disease).

📖 About

• Rare dementia with frontal and anterior temporal lobe involvement.
• Onset usually age 50–70, mean ~58 years.
• Key features: behavioural changes, disinhibition, loss of empathy.

🧬 Aetiology

• Mutations in microtubule-binding protein tau.
• Right prefrontal/anterior temporal lobe → behavioural syndrome.
• Left prefrontal lobe → primary progressive aphasia.

🔬 Pathology

• Neuronal loss and gliosis.
• Spongiform degeneration in superficial cortical layers.
• Pick bodies – round tau-positive intracytoplasmic inclusions.
• Pick cells – large ballooned neurons in superficial cortex.

🔄 Variants

• Behavioural variant FTD – disinhibition, impulsivity, apathy.
• Primary Progressive Aphasia (PPA):
  • Non-fluent variant (agrammatism, effortful speech).
  • Fluent/semantic variant (loss of word meaning).
• Corticobasal degeneration: alien limb, apraxia, stiff jerky limb.
• FTD-MND overlap: FTD may precede motor neurone disease (usually men <65).

👩‍⚕️ Clinical Features

• Behavioural changes early: apathy, disinhibition, overeating, impulsivity.
• Personality change: inappropriate sexual behaviour, poor hygiene, loss of empathy.
• Cognitive decline: loss of executive functions, poor judgement, later memory loss.
• Speech/language: aphasia, dysarthria, loss of fluency.
• Neurological features: akinetic rigidity, limb apraxia, pseudobulbar palsy, spastic dysarthria.
• Advanced: vertical gaze palsy, alien hand syndrome, MND features.

🧪 Investigations

• Bloods: FBC, U&E, LFT, TFT, B12, folate, syphilis screen (exclude reversible causes).
• MRI: frontal and anterior temporal lobe atrophy (may be asymmetrical).
• SPECT/PET: reduced anterior perfusion.
• EEG: usually normal (helps distinguish from Alzheimer’s).
• EMG: if MND suspected.

💊 Management

• ❌ No disease-modifying treatment.
• ❌ Cholinesterase inhibitors / memantine not effective.
• ✅ SSRIs: can help compulsive behaviour, hyperorality, depression.
• ✅ Quetiapine: may be used for behavioural disturbance (short-term).
• ✅ Supportive: MDT care, OT, social services, caregiver support.
• Advance care planning early due to progressive decline.

🧠 Frontotemporal Dementia – Clinical Cases

• Case 1: Behavioural Variant FTD (bvFTD)
  A 58-year-old accountant is brought by his wife because of marked personality change over 18 months. He has become disinhibited, eating excessively, making inappropriate jokes, and neglecting work. There is no memory loss early on, but planning and empathy have deteriorated. Neurological examination is normal except for mild frontal release signs. MRI shows frontal and anterior temporal lobe atrophy; CSF Alzheimer biomarkers are negative.
  Teaching point: bvFTD is characterised by early behavioural disinhibition, apathy, and loss of executive control with preserved episodic memory initially. Misdiagnosis as a psychiatric disorder is common. SSRIs may help behavioural symptoms, but disease-modifying therapy is not yet available.


• Case 2: Primary Progressive Aphasia – Semantic Variant
  A 64-year-old retired teacher presents with a two-year history of progressive word-finding difficulty. She speaks fluently but uses vague terms (“that thing”, “the animal”) and fails to name common objects. Reading aloud is preserved, but comprehension of single words is impaired. Neuro exam is normal. MRI reveals asymmetric (left > right) anterior temporal lobe atrophy. Diagnosis: semantic-variant primary progressive aphasia, a form of FTD.
  Teaching point: Semantic-variant PPA causes loss of word meaning and object recognition, reflecting anterior temporal degeneration. Contrast with the non-fluent/agrammatic variant (effortful speech) and logopenic variant (word-retrieval pauses, usually Alzheimer-related).

💡 Clinical pearl: Think FTD in any patient < 65 years with progressive personality or language change but relatively preserved memory. MRI pattern of frontal ± temporal atrophy clinches the diagnosis. Genetic forms (MAPT, GRN, C9orf72) account for ~30–40% of cases.

Corticobasal degeneration (Dementia)

🧠 Corticobasal Degeneration (CBD) is a rare adult-onset neurodegenerative disorder, classed within atypical parkinsonism and the spectrum of frontotemporal lobar degeneration (FTLD). It often begins with asymmetrical motor symptoms and progresses to include cognitive, behavioural, and language decline. A hallmark sign is the alien limb phenomenon – where a limb seems to act independently.

📌 About

• Also called Corticobasal Ganglionic Degeneration (CBGD).
• A tauopathy - abnormal accumulation of tau protein in neurons and glia.
• Shares pathology with progressive supranuclear palsy (PSP) and frontotemporal dementia (FTD).
• Combines parkinsonism, dystonia, myoclonus, cognitive impairment, and language dysfunction.

⚠️ Aetiology & Pathology

• Tauopathy: abnormal tau protein deposits disrupt neuronal function.
• Key regions affected:
  • Nigrostriatal pathways
  • Thalamus, subthalamic nucleus, globus pallidus
  • Red nucleus and dentate nucleus
• Histology: ballooned neurons and tau-positive inclusions in cortex and basal ganglia.

🩺 Clinical Features

• Asymmetrical parkinsonism: rigidity, bradykinesia (tremor less common than in Parkinson’s disease).
• Alien limb phenomenon: limb moves involuntarily, sometimes interfering with tasks.
• Dystonia: abnormal postures, especially hand clenched with flexed thumb.
• Myoclonus: jerky limb movements.
• Supranuclear gaze palsy: impaired voluntary vertical/horizontal gaze (overlaps with PSP).
• Cognitive & Speech: progressive non-fluent aphasia, apraxia, dementia, behavioural change (disinhibition, depression, emotional blunting).
• Other: postural instability, dysphagia, sensory deficits.

🔬 Investigations

• Bloods: FBC, U&E, ESR/CRP, LFT, TFT, B12, folate – exclude secondary causes.
• MRI: asymmetric frontoparietal cortical atrophy (contralateral to affected side).
• PET/FDG-PET: parietal hypometabolism, reduced fluorodopa uptake in basal ganglia.
• DaTscan (SPECT): abnormal uptake, helps distinguish from idiopathic Parkinson’s disease.
• Neuropsychological tests: memory, executive function, and language deficits.

💊 Management

• Supportive care: MDT approach (neurologist, physiotherapy, speech therapy, OT).
• L-Dopa: trial often ineffective or only transient benefit.
• Behavioural symptoms: quetiapine or other atypical antipsychotics (used cautiously).
• Dystonia/myoclonus: clonazepam, baclofen, valproate, or botulinum toxin.
• Mood disorders: SSRIs for depression or anxiety.
• Speech therapy: vital for dysphasia and swallowing; PEG feeding may be required in advanced stages.
• End-of-life care: focus on comfort, aspiration prevention, and mobility support.

📉 Prognosis

• Steadily progressive neurodegenerative course.
• Median survival: ~6–8 years after onset.
• Mortality often from pneumonia, aspiration, or immobility-related complications.