Dementias

Overview – Dementias

Dementias are a group of acquired, progressive neurodegenerative conditions characterised by global cognitive decline without altered consciousness. Common forms include Alzheimer’s disease, Lewy body dementia, frontotemporal dementia (Pick’s disease), vascular dementia, and age-related senile dementia. Each has unique pathophysiological mechanisms and clinical features. Understanding the distinctions between these syndromes is crucial for diagnosis and management in clinical practice.

Definition

• Dementia = Acquired global impairment of intellect without altered level of consciousness
• Symptoms affect memory, cognition, executive function, language, behaviour

Epidemiology

• Affects ~5% of people >55 years
• 20% prevalence by age 80
• Risk doubles every 5 years past age 60
• 50% have associated behavioural/psychological symptoms

Clinical Diagnosis

• Gradual cognitive decline (starting with memory)
• Behavioural/psychiatric features (agitation, hallucinations, etc.)
• Progressive impact on ADLs (medications, finances, mobility)
• Cognitive screening: MMSE, MOCA

Alzheimer’s Disease

Aetiology

• Most common dementia type
• Multifactorial: genetic and environmental risk
• Early onset in Down syndrome

Pathophysiology

• ↑ β-amyloid → extracellular plaque deposition
• → Neuronal death and synaptic loss
• Also causes cerebral amyloid angiopathy

Morphology

• Severe cortical atrophy, widened sulci, narrow gyri
• Compensatory ventricular dilation (hydrocephalus ex-vacuo)

Clinical Features

• Insidious onset (progresses over years)
• Early: short-term memory loss (hippocampal atrophy)
• Moderate: confusion, language difficulty, apathy
• Late: incontinence, seizures, global dysfunction

Management

• Acetylcholinesterase inhibitors (e.g. donepezil)
• Supportive care

Prognosis

• Mean survival ~7 years from diagnosis
• Common cause of death: aspiration pneumonia

Lewy Body Dementia

Aetiology

• Unknown; may have genetic predisposition

Pathophysiology

• α-synuclein aggregates (Lewy bodies) throughout cortex
• Neuronal degeneration in limbic and cortical areas

Morphology

• Cortical atrophy, especially in frontal/temporal regions

Clinical Features

• Rapid progression (months)
• Fluctuating cognition
• Early visual hallucinations (faces, animals, children)
• Parkinsonism (shuffling gait, cogwheel rigidity)
• Delusions, transient altered consciousness

Management

• Cholinesterase inhibitors (some benefit)
• Avoid antipsychotics (may worsen symptoms)

Frontotemporal Dementia (incl. Pick’s Disease)

Aetiology

• “Pick’s disease”: unknown
• Other FTDs often genetic

Pathophysiology

• Intracellular tau protein accumulation → selective frontal and temporal lobe atrophy

Morphology

• Marked frontal and temporal lobe atrophy
• Parietal and occipital lobes spared

Clinical Features

• Onset between 40–65 years
• Behavioural change precedes memory loss (key distinguishing feature)
• Disinhibition, poor impulse control
• Progressive aphasia (expressive and receptive)
• Preserved memory until late

Vascular Dementia (Multi-Infarct Dementia)

Aetiology

• 2nd most common form
• Due to cumulative brain ischaemia from:
  • Hypertension
  • Atherosclerosis
  • Strokes/TIAs

Pathophysiology

• Stepwise decline after successive CVAs
• May be single large infarct or multiple small infarcts
• Lacunar infarcts, cortical necrosis common

Morphology

• Infarcts visible on MRI/CT
• Lacunar changes, white matter disease

Clinical Features

• Memory loss, poor attention
• Executive dysfunction → impaired ADLs
• History of stroke or vascular risk factors
• Parkinsonism (shuffling gait)

Management

• Preventative only:
  • BP control, lipid management
  • Antiplatelet therapy
  • Lifestyle modification

Age-Related (Senile) Dementia

Aetiology

• Neuronal atrophy due to ageing

Pathophysiology

• Generalised loss of cortical neurons
• ↓ Dendritic branching
• ↑ Gliosis (neurons replaced by glial cells)

Morphology

• Cortical thinning
• Ventricular enlargement
• Thickening of leptomeninges

Clinical Features

• Global cognitive impairment
• Slow progression
• No clear histopathological lesion

Wernicke-Korsakoff Syndrome

Aetiology

• Chronic alcohol use → thiamine (vitamin B1) deficiency

Pathophysiology

• ↓ Thiamine → ↓ glucose metabolism → ATP depletion → neuronal damage
• Mammillary body, cerebellum, cortex affected

Morphology

• Mammillary body atrophy and haemorrhage
• Cerebellar and cortical atrophy

Clinical Features

• Confusion, ataxia, nystagmus
• Anterograde + retrograde amnesia
• Confabulation
• Gait disturbance

Management

• IV thiamine before glucose
• Add vitamin B12 to prevent subacute combined degeneration

Dementia Pugilistica (Chronic Traumatic Encephalopathy)

Aetiology

• Repetitive head trauma (e.g. contact sports)

Pathophysiology

• Repeated sub-concussive injury → axonal damage, gliosis, neurodegeneration

Morphology

• Hydrocephalus
• Thinning of corpus callosum
• Cerebellar atrophy

Clinical Features

• Gait ataxia
• Cognitive decline
• Dysphasia
• Parkinsonism
• Personality changes

Summary – Dementias

Dementias are a spectrum of neurodegenerative disorders with distinct pathological and clinical profiles. Alzheimer’s disease is the most common, but vascular, Lewy body, and frontotemporal dementias are also important to recognise. Each form has unique diagnostic features and management strategies. For a broader context, see our Nervous System Overview page.