11th August 2024

Alzheimer’s disease

Overview of Alzheimer’s disease

Alzheimer’s disease is the most common dementia in adults of all ages. There is an initial deficit in episodic memory that progresses to include executive functioning, attention, language and visuospatial skills as the disease advances. Neuropsychiatric symptoms can be prominent, including mood disturbance, anxiety, hallucinations, agitation and restlessness. End-stage disease resulting additionally in reduced mobility, incontinence and inability to communicate can require high levels of care.

The histopathological hallmark of Alzheimer’s disease is cerebral cortical accumulation of beta amyloid (Aβ) plaques and neurofibrillary tangles.

Diagnosis of Alzheimer’s disease

Diagnosis is clinical and made from history, examination, investigations to exclude reversible causes and cognitive testing such as mini-mental state examination (MMSE) or Montreal Cognitive Assessment (MoCA) demonstrating deficits in short-term memory with reduction of category fluence (naming as many items of a category beginning a specific letter) and deficit in visuospatial tasks (copying 3D drawings/clocks) in more advanced disease.

Cognitive testing is complemented by structural correlates on MRI brain, with hallmark symmetrical medial temporal lobe and hippocampal atrophy in early disease and later inclusion of the parietal lobes.

CSF examination has a typical pattern of elevated tau protein and reduced Aβ1-42, but this is not routinely required.

Histological diagnosis is rarely acquired outside of post-mortem. Silver staining and specific tau protein immunohistochemistry demonstrate neurofibrillary tangles within neurons.

Management of Alzheimer’s disease

The mainstay of management is supportive and multidisciplinary. In early stages of disease, management should be proactive in providing education to patients and family, support for advanced care and financial planning whilst capacity is retained and facilitating everyday activities with assistance. Coordination across services such as a community dementia team, day centres, care agencies and GPs is key. With further disease progression and in advanced dementia, care may be better provided in a residential or nursing home setting with consideration of carer respite.

Pharmacological management aims to slow disease progression and prolong time before requiring 24-hour care. The main classes of drugs are anticholinesterases and NMDA receptor antagonists.

Donepezil, galantamine and rivastigmine are acetylcholinesterase inhibitors (AChEi) that are licensed for treatment of mild-to-moderate Alzheimer’s disease. Treatment should be initiated by a clinician with relevant specialist expertise in diagnosis and management of Alzheimer’s. A small but consistent benefit to cognitive function with AChEis compared to placebo has been demonstrated in meta-analyses with some evidence to suggest that withdrawal of treatment may be associated with worsening cognition. Common side effects of AChEis include gastrointestinal manifestations – diarrhoea, vomiting, nausea, reduced appetite, dyspepsia – as well as dizziness, muscle cramps and insomnia. Significant caution should be exercised in patients with bradycardia, heart block or recurrent syncope.

Memantine, an NMDA receptor antagonist, can be considered as an additional agent in individuals already on AChEis with disease progression or as a single agent in individuals with severe Alzheimer’s or those with moderate Alzheimer’s for whom AChEis is contraindicated.

The management of behavioural and psychological symptoms such as aggression or depression is less well evidenced. Conservative approaches addressing surroundings and care should be attempted before consideration of antidepressants and antipsychotics, under specialist guidance, particularly as atypical antipsychotics are associated with increased risk of stroke and mortality in this cohort.