Memory loss

Most older people with memory loss do not have dementia. Depression is clearly a possible diagnosis in Alan’s case, as depressive symptoms can mimic dementia. People who have a first episode of depression in late life have a higher risk of risk of developing dementia. Although consumption of large amounts of alcohol may be associated with alcohol-related dementia, consumption of small amounts is associated with decreased risk of dementia.1 In Alan’s case, a lack of rapid onset, lack of other neurological signs and relatively normal results of brain imaging rule out encephalopathy, brain tumour and stroke.

Alan underwent detailed neuropsychological testing because of his difficulty in retaining new information, and because of the couple’s strong concerns about cognitive decline. He also had blood tests and a CT scan to exclude the presence of reversible causes of dementia or cognitive impairment, such as communicating hydrocephalus, hypothyroidism, and renal and liver dysfunction (Box 3). Although such investigations rarely lead to interventions that result in the reversal of cognitive deficits, they are considered best practice4 and can be routinely organised by GPs. The management of depression may mitigate some of the apparent cognitive deficits. Of people who present with reversible dementia and show improvement, almost half are affected by depression or adverse effects of medications.

There are currently no laboratory and imaging tests that are helpful in predicting the course of MCI or useful for identifying people who will develop dementia. There is some interest in tests that may indicate an increased risk of Alzheimer’s disease (eg, low amyloid-β1-42 or increased total tau protein in the cerebrospinal fluid, or bilateral reduction of glucose metabolism in temporal and parietal regions), but these have no clinical utility at present. Although positive results of such tests may be associated with an increase in risk of dementia, this increase has not been quantified in specific clinical situations, such as Alan’s.

It took 3 years for Alan to “convert” to dementia, which is typical. The yearly conversion rate for people who present with MCI to memory clinics is about 15%.5 People with MCI who do not present to memory clinics show a lower conversion rate, and as many as 20% of them improve or no longer fulfil the research criteria for the diagnosis of MCI after 1 or 2 years.6,7

The clinical assessment of a patient with cognitive impairment demands a structured approach. The first objective is to determine the pattern of cognitive and behavioural deficit. While the MMSE is the most widely known and “tolerably useful” brief structured method of assessing cognitive function, it is insensitive to MCI and strongly influenced by educational level, culture, anxiety and neurological impairment, particularly language and deafness. Moreover, it tends to focus on memory, language and literacy skills, at the expense of non-dominant visuospatial skills and, apart from the mental tracking associated with the “serial sevens” task, includes no assessment of judgement and reasoning (and social behaviour) processed in the frontal lobe. Thus, the MMSE often needs to be supplemented by other tests and supporting history from a reliable family observer. The second objective is to determine any involvement of the nervous system more generally (eg, impaired vertical gaze, dysphasia, tremor, bradykinesia, pyramidal signs). Finally, the general examination should not be overlooked as clues to aetiology of cognitive impairment may lie outside the nervous system (eg, liver disease, sleep apnoea, drugs).

Alzheimer’s disease, vascular dementia, frontotemporal dementia and dementia with Lewy bodies are the most common dementias, both in older people and younger adults. Although all have some impairment of episodic memory, there is wide variation in the degree of associated changes in behaviour, personality and language abilities, as well as the course of these conditions due to differences in the underlying neuropathological conditions. The current view is that people with the clinical picture of Alzheimer’s disease present with overlapping neuropathological conditions (eg, neurofibrillary tangles and senile plaques together with cerebrovascular changes), but the insidious onset and lack of focal neurological signs in Alan’s case make a predominant vascular dementia less likely. The absence of visual hallucinations, fluctuating course and extrapyramidal signs suggest that the diagnosis of dementia with Lewy bodies is improbable.

Memory clinics funded by state health services, such as the Cognitive, Dementia and Memory Service throughout metropolitan and regional Victoria, are becoming increasing available. These clinics not only allow team-based multidisciplinary assessment of people with memory loss (typically with a geriatrician, psychogeriatrician, neurologist, neuropsychologist, nurse, social worker, occupational therapist and speech pathologist [Box 4]) and management of people with dementia, but also provide links to other service providers such as home and community care providers and community supports such as Alzheimer’s Australia support groups. Memory clinics operate within a shared-care model, with a GP providing ongoing medical care and liaising with other specialists. There is some evidence that memory clinics improve the quality of life of carers and improve the assessment of people with dementia.5 Although there are few such clinics in rural settings, some clinics have extended their reach using telehealth.

Having made a diagnosis of probable Alzheimer’s disease, there is good evidence from RCTs and meta-analyses that the use of cholinesterase inhibitors (which increase the availability of central acetylcholine) is associated with symptomatic benefits, including improvements in memory and general mental functioning, and enhanced quality of life.9 The cholinesterase inhibitors donepezil, galantamine and rivastigmine are all subsidised by the Pharmaceutical Benefits Scheme (PBS) for the treatment of mild to moderate Alzheimer’s disease, defined by an MMSE score ≥10. Treatment with memantine, a moderate affinity N-methyl-D-aspartate receptor antagonist that also provides symptomatic relief and enhances quality of life, can be initiated for people with moderate Alzheimer’s disease (MMSE score 10–14); however, memantine does not currently qualify for a PBS benefit if it is prescribed concurrently with a cholinesterase inhibitor. None of these agents alter the progression of the disease. Also, these agents can only be prescribed on the PBS for more than 6 months if there is objective evidence of improved cognitive performance during the initial 6 months of treatment, which is defined as a 2-point increase in MMSE score (or a 4-point decrease on the cognitive section of the Alzheimer Disease Assessment Scale10 or, in specific circumstances, improvement on the Clinician’s Interview-Based Impression of Change11).

Alan was 78 years of age at the time of his death and had lived with the diagnosis of Alzheimer’s disease for 2.5 years. The median duration of survival for people with dementia is 4.5 years from the time of diagnosis,12 but this is highly variable and some people survive for as long as 20 years. Physical complaints are a major problem for the majority of people with dementia. Many people with dementia die from other causes, as in Alan’s case, but the presence of dementia is a contributing factor. In Australia, Alzheimer’s disease and dementia (with advanced debility) is the third leading cause of death in women and the sixth leading cause of death in men.13

Nine in 10 people with Alzheimer’s disease will develop behavioural and psychological symptoms of dementia (BPSD) during the course of their illness.14 There is some evidence that atypical antipsychotics such as risperidone may be effective in decreasing agitation and psychotic symptoms, but their use increases the risk of cardiovascular events and death (Level A evidence).14 The efficacy of antidepressants in treating depressive symptoms associated with dementia or MCI has not been established and antidepressants may increase the risk of delirium and falls. Hence, non-pharmacological interventions (eg, identifying and avoiding situations that trigger distress) should be considered before psychotropic medications for the treatment of BPSD (Level C evidence). The presence of pain can also exacerbate behavioural symptoms in people with dementia. In addition, people with dementia seem to be particularly susceptible to the development of delirium, which may be triggered by infections, metabolic imbalances, and a wide range of drugs (particularly sedatives and analgesics).

A major determinant of quality of life and ability to remain at home for people with dementia is the continuing support of a carer. Support for carers, such as timely access to information and services, enables people with dementia to maintain maximum quality of life in non-residential care settings. Aged Care Assessment Teams are often a helpful starting point for access to these services. The Australian Government, as part of the Dementia Initiative, has funded the Dementia Behaviour Management Advisory Service, a nationwide network of services that provide advice for patients and their carers, and the Dementia resource guide (http://www.health.gov.au/internet/main/publishing.nsf/Content/ageing-dementia-info-hp.htm). In addition, Alzheimer’s Australia provides support groups and various other types of support — such as counselling services — in each state (http://www.fightdementia.org.au).

4 Neuropsychologist assessing a patient with memory problems