Alzheimer disease (Dementia) ✅

Related Subjects: |Behavioural and Psychological (BPSD) Symptoms of Dementia |Alzheimer disease (Dementia)

🧠 Alzheimer’s disease is the most common cause of dementia. It causes a gradual, progressive decline in memory, thinking, language, behaviour and daily function. Diagnosis is clinical, supported by collateral history, cognitive testing, examination and investigations to exclude reversible or alternative causes.

ℹ️ About

• Alzheimer’s disease usually presents insidiously with progressive short-term memory loss, impaired learning, word-finding difficulty and reduced ability to manage daily activities.
• Collateral history from a family member or carer is essential, as patients may lack insight into functional decline.
• Progression is typically gradual, unlike vascular dementia, which may show a stepwise decline.
• Delirium, depression, medicines, alcohol, sensory impairment and metabolic disturbance can mimic or worsen cognitive symptoms.

🧬 Pathophysiology

• Alzheimer’s disease is associated with synaptic failure, neuronal loss and cerebral atrophy, especially in the hippocampus and medial temporal lobes.
• β-amyloid plaques are extracellular deposits that disrupt neuronal signalling and trigger inflammation.
• Neurofibrillary tangles are intracellular aggregates of hyperphosphorylated tau protein and correlate with disease severity.
• Loss of cholinergic neurons contributes to problems with memory and attention, which is why acetylcholinesterase inhibitors can provide symptomatic benefit.
• Most cases are sporadic; rare familial forms are linked to mutations such as APP, PSEN1 and PSEN2. ApoE ε4 increases risk but is not used as a routine diagnostic test.

⚠️ Risk Factors

• Increasing age is the strongest risk factor; Alzheimer’s disease becomes much more common in later life.
• Family history increases risk, especially if there is early-onset dementia in a first-degree relative.
• Genetics: ApoE ε4 increases susceptibility, while rare mutations such as APP, PSEN1 and PSEN2 can cause familial early-onset Alzheimer’s disease.
• Cardiovascular risk factors such as hypertension, diabetes, smoking, obesity and hyperlipidaemia are associated with increased dementia risk.
• Previous head injury, especially repeated traumatic brain injury, may increase risk.
• Lower cognitive reserve, social isolation, physical inactivity, hearing loss and depression are associated with higher dementia risk.
• Alcohol excess and poor sleep may contribute to cognitive decline and should be addressed as part of prevention and assessment.

💡 Clinical Pearl: Risk factors are not diagnostic. In practice, they help identify people who may benefit from prevention advice, medication review, vascular risk optimisation and earlier assessment if symptoms develop.

🔎 Assessment

• Take a history from the patient and an informant, focusing on onset, progression, memory, language, visuospatial skills, behaviour, mood, medicines, alcohol and activities of daily living.
• Use a structured cognitive tool such as MoCA, MMSE, 6CIT or ACE-III, but do not rely on a score alone.
• Assess function, falls risk, driving, safeguarding, capacity, carer strain and home safety.
• Screen for depression and delirium, especially if symptoms are fluctuating or sudden in onset.

🧪 Investigations

• Blood tests commonly include FBC, U&Es, LFTs, calcium, glucose/HbA1c, TFTs, B12 and folate.
• Consider urine testing, infection screen or other tests if clinically indicated.
• Medication review is important: anticholinergics, sedatives, opioids, benzodiazepines and alcohol may worsen cognition.
• Structural imaging with CT or MRI can help exclude tumour, subdural haematoma, normal-pressure hydrocephalus or significant vascular disease.
• Specialist services may use MRI patterns, FDG-PET, amyloid imaging or CSF biomarkers where diagnosis remains uncertain.

🖥️ Imaging Features

• MRI: medial temporal and hippocampal atrophy support Alzheimer’s disease.
• CT: may show cerebral atrophy and helps exclude other structural pathology.
• Vascular changes: prominent small-vessel disease or infarcts may suggest vascular or mixed dementia.
• Imaging supports the diagnosis but does not replace clinical assessment.

👩‍⚕️ Behavioural and Psychological Symptoms

• Symptoms may include anxiety, depression, apathy, agitation, sleep disturbance, wandering, hallucinations, delusions or aggression.
• Look for triggers: pain, constipation, urinary retention, infection, dehydration, hunger, overstimulation, sleep disruption or environmental change.
• Use non-drug strategies first: reassurance, routine, orientation cues, calm communication, activity, sleep hygiene and carer support.
• Antipsychotics should only be considered if the person is severely distressed or there is risk of harm, and after discussing risks and benefits.
• Avoid antipsychotics where possible in dementia with Lewy bodies or Parkinson’s disease dementia because of severe sensitivity reactions.

💊 NICE-Compatible Drug Treatment

🏡 Non-Drug Management

• Offer cognitive stimulation therapy for people with mild-to-moderate dementia where available.
• Encourage physical activity, social engagement, good sleep, hearing and vision optimisation, nutrition and hydration.
• Support carers with education, respite planning, crisis contacts and assessment of carer strain.
• Review driving, work, finances, lasting power of attorney and advance care planning early while the person has capacity.
• Optimise vascular risk factors such as hypertension, diabetes, smoking and hyperlipidaemia, especially where mixed dementia is possible.

⚠️ Complications

• Falls, fractures, wandering, malnutrition, dehydration and medication errors.
• Delirium triggered by infection, constipation, pain, dehydration or hospital admission.
• Swallowing difficulty, aspiration pneumonia, pressure ulcers and immobility in advanced disease.
• Carer burnout, safeguarding concerns and loss of independence.

🌅 Advanced Disease and End-of-Life Care

• Focus on comfort, dignity, nutrition, hydration, pressure care, mouth care and symptom control.
• Discuss ceilings of care, hospital transfer, resuscitation status and preferred place of care early and sensitively.
• Support families and carers, as dementia is a long illness with major emotional and practical burden.

💡 Exam Pearl: Alzheimer’s disease usually causes gradual progressive memory impairment with hippocampal or medial temporal atrophy. Stepwise decline suggests vascular dementia; prominent early hallucinations, fluctuating cognition and parkinsonism suggest dementia with Lewy bodies.

📚 NICE Guidance

• NICE NG97: Dementia: assessment, management and support for people living with dementia and their carers.
• NICE TA217: Donepezil, galantamine, rivastigmine and memantine for the treatment of Alzheimer’s disease.
• NICE QS184: Dementia quality standard.