29th April 2024

Dementia and Cognition in Old Age

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/

Dementia; subtypes & mimics

Background

Besides Alzheimer’s Disease, there are a number of other recognised dementia subtypes. These subtypes have their own distinct pathophysiology. As a result, each dementia subtype has identifying features that are characteristic to them in terms of presenting features, symptomology or disease progression. Identification of dementia subtypes is essential as management can vary depending on the subtype.

Dementia subtypes

Dementia with Lewy bodies and Parkinson’s disease dementia

Dementia with Lewy bodies (DLB) and Parkinson’s disease dementia (PDD) share many features, with the distinction between them being the onset of symptomatology. In DLB, there is progressive cognitive decline, similar to that of Alzheimer’s dementia, with subsequent onset of motor features in the form of parkinsonism. In PDD, the motor feature precedes the onset of the cognitive symptoms by at least one year. These dementia subtypes are characterised by Visual hallucinations, sleep disorders (especially REM sleep behaviour disorders) and depression.

Both DLB and PDD are characterised by the presence of intraneuronal inclusions containing synuclein and ubiquitin in the brain stem, limbic regions and forebrain, known as Lewy bodies. The diagnosis of DLB and PDD should be made in a specialist dementia diagnostic service, however if diagnosis is uncertain, I-FP-CIT SPECT (sometimes known as a DaTscan) should be utilised.  I-MIG cardiac scintigraphy can be used if I-FP-CIT SPECT is not available.

Vascular dementia

Vascular dementia (VD) is the second most common subtype of dementia after Alzheimer’s Disease and can co-exist with Alzheimer’s Disease. VD is caused by thromboembolic or hypertensive infarction of small and medium size vasculature in the brain. Onset and clinical features can vary. A Cognitive deficit can present suddenly following a single vascular event, or multiple events can lead to stepwise cognitive deficit with periods of stable disease between events. The latter is sometimes referred to as multiple-infarct dementia. Finally, there can be progressive small vessel disease caused by multiple micro-vessel infarcts; this can present in a slowly progressive cognitive decline.

Diagnosis can be made in a specialist dementia diagnostic service aided by MRI imaging where needed. CT imaging can be used if MRI imaging is not possible.

Management of VD revolves around managing vascular risk factors. This can include optimisation of hypertension, cholesterol, diabetes and using antiplatelet/anticoagulation where appropriate.  Acetylcholinesterase inhibitors and memantine should only be used if co-existent AD is thought to be present.

Frontotemporal lobe dementia

Frontotemporal lobe dementia (FTD) is a spectrum of neurodegenerative syndromes affecting the frontal and temporal lobes of the brain. FTD is typically of gradual onset but is progressive over time. Frontal lobe symptoms include personality and behavioural change, emotional blunting and disinhibition. Temporal lobe symptoms include a progressive decline in speech function. This can include progressive word finding difficulties and challenges with language fluency. Memory normally remains intact.

The onset of FTD is often younger, involving patients between the ages of 45 and 65. However, it is the third most common dementia in individuals over 65 years of age. FTD is caused by abnormal deposition of intracellular proteins in the frontal and temporal lobe that trigger the degeneration of neurons. Different protein aggregates have been identified for different FTD syndromes.

CT or MRI imaging normally shows bilateral asymmetrical abnormalities within the frontal and temporal lobes. If diagnosis is uncertain, Fluorodeoxyglucose (FDG) PET or perfusion SPECT can be used.

There are no known effective pharmacological interventions for FTD.

Dementia Mimics

A number of conditions can mimic dementia. The most commonly encountered in the inpatient hospital environment is delirium, however depression and mild cognitive impairment can also be confused for dementia. It is important to have an understanding of the distinctions and how they would apply to clinical practice. Mild cognitive impairment is cognitive decline beyond what would be expected for someone’s age and can be seen as a pre-dementia state. Sporadic Creutzfeldt-Jakob Disease, pellagra, Korsakoff’s syndrome and normal pressure hydrocephalus are other conditions which may be confused with, or overlap dementia.

References

• National Institute for Health and Care Excellence (UK). Dementia: assessment, management and support for people living with dementia and their carers. London; 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.). https://icd.who.int/