Mixed Alzheimer and Vascular Dementia

Mixed dementia is the coexistence of Alzheimer disease pathology and cerebrovascular disease, each contributing to cognitive decline. It is the commonest form of dementia in the very old and is underdiagnosed during life.

At autopsy it is found in a large proportion of people with dementia, and its frequency increases with age.

Pathophysiology. Amyloid and tau accumulation combines with infarcts, white matter damage, microbleeds and hypoperfusion. Vascular injury lowers the threshold at which Alzheimer pathology produces dementia. Shared risks include hypertension, diabetes, smoking, atrial fibrillation and APOE e4.

Gradual memory loss typical of Alzheimer disease together with executive slowing, apathy, gait disturbance, urinary urgency and sometimes stepwise decline after strokes. Focal signs and mood change are common.

Assess cognition, function and vascular risk. MRI shows medial temporal atrophy together with infarcts, extensive white matter hyperintensities and microbleeds. Amyloid and tau biomarkers (CSF or PET, where available) confirm the Alzheimer component. Blood tests exclude reversible causes: thyroid function, vitamin B12, folate, glucose, calcium, renal and liver tests.

Differential diagnosis.

• Pure Alzheimer disease or pure vascular dementia.
• Lewy body dementia, frontotemporal dementia and normal pressure hydrocephalus.
• Depression, delirium and drug effects.

Control vascular risk: blood pressure (aim for about 130/80 mmHg if tolerated without postural hypotension), lipids with a statin, diabetes, smoking cessation, and antiplatelet or anticoagulant therapy as indicated.

For symptoms, give donepezil 5 mg at night, increased to 10 mg after 4 weeks, or rivastigmine or galantamine, and consider memantine 5 mg daily increased weekly by 5 mg to 20 mg daily for moderate to severe disease (maximum 10 mg daily when eGFR is under 30 mL/min). Monitor heart rate, syncope and weight on cholinesterase inhibitors.

Anti-amyloid antibodies are usually unsuitable because of microbleeds, extensive white matter disease and anticoagulant use. Provide exercise, cognitive and social activity, carer support and advance care planning.

Monitoring. Cognition, function, blood pressure and carer strain every 6 months.