29th April 2024

Alzheimer’s disease

Background

Dementia is a syndrome characterised by progressive, normally irreversible, global cognitive decline. ICD-10 definition states that the cognitive decline needs to be in two or more cognitive domains and assessed in the context of the individual’s age and premorbid cognitive function. The most common presenting feature is memory impairment, but it’s important to consider other cognitive domains (language, frontal executive function, visuospatial function, apraxia and agnosia).

The aetiology of dementia is vast, the most common being Alzheimer’s Disease (AD), which accounts for 62% of all dementias. AD is a progressive neurodegenerative form of dementia characterised by failing memory and disturbance to daily functioning. AD is believed to be caused by deposition of amyloid peptides (extracellular) and Neurofibrillary tangles (intracellular) within the cerebral cortex and subcortical grey matter. Progressive deposition correlates with advancing disease through progressive loss of neurons and synapses, resulting in cerebral atrophy.

Risk factors

The most significant risk factor for AD is age, commonly affecting people over the age of 65. The prevalence increases with age, with risk doubling every five years past the age of 65. A small percentage of cases occur prior to the age of 65; this is referred to as early-onset Alzheimer’s Disease.

Other risk factors include being female, leading an unhealthy lifestyle (similar to cardiovascular risk factors) and having Down Syndrome. Family history is also significant, with a family history of AD, Parkinson’s disease and Down’s Syndrome resulting in an increased risk of suffering with AD.

Clinical features

Mild cognitive impairment, often in the form of mild memory impairment, will often precede the onset of AD.  The most common clinical feature is memory impairment. Classically episodic memory is affected in a temporal gradient. Distant memories are preserved for longer, with the loss of more recent events more prevalent. Working memory tends to be preserved but there is a progressive loss in the ability to learn, process, and retain new information.

As the AD advances, deterioration in other cognitive domains becomes more apparent. Language impairment is reflective of a decline in semantic and pragmatic language processing. Semantic language involves language content and fluency whilst pragmatic language involves language adaptation in social interactions.

Other common deficits include an inability to carry out skilled tasks (apraxia) and failure to recognise objects, people and places (agnosia). AD affects the ability to organise and plan. These cognitive deficits become more pronounced and progress as the AD advances.

Besides the decline across cognitive domains, AD can present with psychiatric symptoms including delusions, hallucinations and mood disorders including depression. Behavioural symptoms can also manifest, including personality changes, aggression, wandering and searching.

End stage AD can leave a person fully dependent on professionals for their care needs with marked global physical decline.

Diagnosis

AD, like other subtypes of dementia, should be formally diagnosed by a specialist dementia diagnostic service. However, prior to a referral, investigations should be sought to establish whether a reversible cause is present for the patient’s symptoms.

Initial assessment should include a clinical history, a collateral history, a physical examination, a drug history review and appropriate blood and urine investigations to exclude reversible pathology. Cognitive testing tools should also be utilised to aid assessment. Specialist dementia diagnostic services will carry out neuropsychological testing and pursue other appropriate investigations as per validated diagnostic criteria.

Imaging modalities such as CT scanning can be used to rule out structural pathology, and MRI imaging can be used to identify patterns of cerebral atrophy to further confirm the diagnosis.

If, despite these investigations, a diagnosis of AD is still uncertain, Fluorodeoxyglucose-positron emission tomography- CT (FDG-PET) or Perfusion single photon emission CT (SPECT) can be considered, as can CSF examination. Apolipoprotein E genotyping or EEG should not be used to diagnose AD.

Management

Nonpharmacological interventions such as group cognitive stimulation or reminiscence should be offered as appropriate, as well as an occupational therapist input to support function. Emotional support should be considered for the patient and carers, as well as support with advanced care planning.

Pharmacological intervention includes the use of acetylcholinesterase inhibitors (AChE-I) in mild to moderate AD with the goal of slowing the progression of AD. In moderate to severe AD, Memantine can be used in addition to acetylcholinesterase inhibitors or as monotherapy. Antipsychotics can be considered with caution in the management of psychiatric symptoms.

References

• Ferris SH, Farlow M. Language impairment in Alzheimer’s disease and benefits of acetylcholinesterase inhibitors. Clin Interv Aging. 2013;8:1007-14. doi: 10.2147/CIA.S39959. Epub 2013 Aug 2. PMID: 23946647; PMCID: PMC3739421
• Kinney JW, Bemiller SM, Murtishaw AS, Leisgang AM, Salazar AM, Lamb BT. Inflammation as a central mechanism in Alzheimer’s disease. Alzheimers Dement (N Y). 2018 Sep 6;4:575-590. doi: 10.1016/j.trci.2018.06.014. PMID: 30406177; PMCID: PMC6214864
• National Institute for Health and Care Excellence (UK). Dementia: assessment, management and support for people living with dementia and their careers. London: National Institute for Health and Care Excellence (UK); 2018 June. (NICE Guideline, No 97. Available from https://www.nice.org.uk/guidance/ng97
• World Health Organization (2019). International Statistical Classification of Diseases and Related Health Problems (11th ed.). Available from https://icd.who.int/