Brain ageing is generally thought of as atrophy, a more or less pathological loss of neurones, leading to cognitive deficits and functional impairment, if not clear-cut symptoms and signs of dementia. This model is likely to be relevant for the dementias,2 or for brain changes associated with systemic, especially vascular pathologies.3, 4 There are, however, also physiological reductions in cell numbers, connectivity and brain plasticity during the life span, right from birth, that may play an important role in the adjustment of brain function to the changing roles of the individual (see box 1, right).1

Normal ageing

There is general agreement that cognitive speed, inhibitory function, and memory performance decline with age while crystallised, particularly verbal, abilities remain largely intact in those who survive for long-term follow-up.5

The following factors appear to predict faster cognitive decline:5

• poor health
• fewer years of education
• lower activity
• the presence of the APOE ε4 allele (which appears associated with age-related cognitive impairment, cardiovascular disease, Alzheimer's disease, and poor outcome after brain trauma)
• high blood pressure

Age-related reductions in hippocampal function and particularly in plasticity may account for some of these changes.6 Typically, however, the brain is not a passive organ that just shows local underactivity in the affected region. Compensatory additional recruitment of neurones occurs mainly in prefrontal brain areas (see figure 1, above) to back up compromised functions.7, 8 This may explain the observation that older people may perform as well as their younger peers by using alternative strategies. How effectively such prefrontal scaffolding works, will affect the speed of functional deterioration. It is likely that compensatory mechanisms rather than the primary deficit associated with declining short-term memory are modified by training, so they should be the focus of remedial strategies against cognitive deterioration.7

Halting decline

What measures, if any, can be taken to halt decline in function? This question can only be answered by randomised controlled trials. There is a temptation to infer risks and benefits from association studies, but unfortunately there is often no correspondence between the results of cohort or

case-control studies which may be confounded, and the properly controlled randomised studies.9

Tables 1-4, above and opposite, summarise recent reviews of studies examing risk factors and interventions to ameliorate cognitive decline.

Evidence of benefit

Alcohol: Drinking small to moderate amounts of alcohol appears to confer some benefit (see table 1, above).

Stopping smoking: Both smoking and diabetes increase the risk of all types of dementia (see table 2, above), not smoking or even stopping smoking reduces this risk, but better control of type 2 diabetes does not appear to have a measurable effect (although the most recent review was carried out in 2002).10

Evidence of no benefit

There is some evidence that the following are NOT helpful (see table 3, opposite):

• HRT
• DHEA supplementation
• BP lowering in patients without prior cerebrovascular disease
• statins
• vitamin B6
• procaine

Usefulness under debate

The usefulness of the following remains CONTROVERSIAL (see table 4, opposite) as there is insufficient evidence to establish or refute a beneficial effect:

• exercise
• treatment of type 2 diabetes
• omega-3 fatty acids
• folic acid with or without vitamin B12
• antioxidant vitamins
• ginkgo biloba

Diagnosing dementia

Dementia is diagnosed in the presence of objective cognitive impairment, both long- and short-term memory, plus at least one additional (cortical) cognitive deficit, such as:

• dysphasia
• dyspraxia
• agnosia
• disturbance in executive functioning (e.g. planning, organising, sequencing)

In addition, patients have to show:

• significant impairment in social or occupational functioning and a significant decline from previous levels32

Any evidence of the following may point towards alternative causes of cognitive deterioration:

• cerebrovascular disease
• Parkinson's disease
• Huntington's disease
• subdural haematoma
• normal-pressure hydrocephalus
• brain tumour

Thus, any localising neurological symptoms and signs require careful evaluation to exclude treatable disease.

Depression

Depressive symptoms are more prevalent than dementia in the community.33 Clinical (major) depression can present with cognitive deterioration, often associated with subjective complaints. Obviously any sign of low mood is suggestive of depressive aetiology, but also evidence of diurnal variation, especially with worse symptoms in the morning, psychomotor slowing, anxiety and agitation, disturbance of sleep, appetite and motivation.

Disproportionately severe deterioration particularly with complaints of poor memory or ‘something wrong with the brain', in the absence of signals of underlying physical illness should prompt a review of depressive symptoms.

Delirium

The other cause of rapid cognitive deterioration, delirium, is characterised by evidence of underlying physical disease, sometimes trivial such as urinary tract infection, and psychiatric symptoms, such as (visual) hallucinations, anxiety, agitation, and disorientation.

Conclusion

Patients presenting with cognitive deterioration, i.e. subjective deterioration or decline observed by their family, require an estimation of degree of functional impairment relative to pre-morbid levels if any, and then a systematic evaluation of physical and mental state, with referral to memory clinics or other specialist assessment if necessary.34

Patients with subjective or objective memory impairment, but without functional deterioration, can be referred to the local memory clinic (where available), while demented patients eligible for acetylcholinesterase inhibitor treatment, patients whose diagnosis is unclear and who may need some specific investigations, as well as patients who may benefit from a combined approach with psychotropic drugs and behavioural support should be referred to the local mental health team.34

If patients are depressed, referral may be indicated if: the first or later line of antidepressant treatment fails; patients are acutely psychotic, suicidal or at risk of self-neglect; or if a specialist psychotherapeutic intervention appears warranted.33