Will I lose my marbles doc?

Many doctors will hear this question from anxious patients over the next few years. People want to know if they face the risk of dementia or Alzheimer’s disease as they grow older. The ‘Baby Boomer’ generation is now starting to retire and large numbers of Australians in their 60s will dominate the older age demographic. Many of these individuals will have seen parents succumb to dementia and will be wondering whether this fate awaits them too.

The fact that Australia has been so successful in prolonging the life-span of its citizens (we are now fifth after Japan, Hong Kong, Iceland and Switzerland in life expectancy) through prevention strategies such as immunization and public health programs, low levels of social and economic disadvantage, good diet and lowering levels of smoking, as well as an affordable and universal health system, has meant that while we are escaping the consequences of many illnesses that prematurely cause death, our longevity now exposes us to conditions that increase dramatically with age.

The incidence Alzheimer’s disease and other common causes of dementia (vascular cognitive impairment, and Lewy body dementia associated with Parkinson’s conditions) increase exponentially with age after the age of 65 years. While less than one percent of the population under the age of 65 suffers from dementia the proportion increases to 20 percent in over 80s individuals, to about 50 percent in persons aged in the 90s. Given these alarming statistics it is little wonder why patients (and you and me!) want to know their risk profile.

At the moment there are no dementia risk profile calculators available like there are for the risk of cardiovascular disease. However, a number of risk factors for Alzheimer’s disease are known.


Age is the most powerful predictor of the incidence of Alzheimer’s disease as noted above. Apart from getting into a reverse time machine there is nothing much we can do about this risk factor. If one has to age then we should try to do it healthily and this may confrere some protection (see below). Some very unfortunate patients develop dementia at a young age. The early onset cases of Alzheimer’s disease and other less common early onset dementias (like frontotemporal dementia) are more likely to be associated with genetic influences. So what about genes as a risk factor?


Most cases of Alzheimer’s disease that develop over age 65 are sporadic, that is not linked to a specific gene mutation. But one gene may increase the risk of late onset Alzheimer’s disease – the apolipoprotein E (ApoE) gene. This gene has three variants or alleles; E2, E3, and E4. While the E2 and E3 variant do not carry increased risk the E4 variant (especially if there are two copies – E4/E4) does increase the risk of Alzheimer’s disease over and above the background risk based on age. The ApoE status of a patient can be obtained from a simple blood test done by most pathology companies (but this test is not MBS subsidised). Younger onset Alzheimer’s disease (in the 40s, 50s and early 60s age groups) often has a familial pattern and is uncommon – accounting for only 5-10 percent of all cases. Three genes are implicated – Presenilin 1, Presenilin 2, and Amyloid Precurser Protien genes. The exact effect of mutations to these genes is not fully appreciated but probably involves alterations to the structure and function of amyloid protein leading to accumulation within the brain.


At some level (as yet not clearly identified) the pathophysiology of Alzheimer’s disease involves inflammatory processes. Amyloid plaques attract immune cells. Anti-inflammatory drugs (especially non-steroidals used for arthritis) seem to lower the risk of Alzheimer’s disease and may provide some small comfort for those exposed to these drugs over prolonged periods of time. Unfortunately, trials of NSAIDs have not been successful in treatment of established Alzheimer’s disease.

Cardiovascular risk factors

One of the surprising findings of research into the dementia field is that while post mortem brain examinations often find widespread Alzheimer’s disease changes (plaques, tangles) there is no corresponding evidence of clinical dementia in the individual before death. However, when the Alzheimer’s changes are accompanied by evidence of vascular CNS pathology then ante-mortem history of dementia symptoms is more common. This raises the possibility that the combination of Alzheimer’s pathology with vascular changes is the most likely to lead to clinical dementia. Widespread use of MRI imaging has led to an appreciation of the high prevalence of deep white matter ischemic changes as an index of subtle cerebrovascular disease in older individuals. The finding that the clinical expression of Alzheimer’s disease may be reliant in part on vascular disease indicates that the presence of vascular risk factors is an important factor in increasing the risk of dementia. Individuals with hypertension, high cholesterol and lipids, high levels of homocysteine, diabetes, poor cardiovascular fitness and obesity, and who are smokers are at increased risk of dementia.


Women seem to be more highly represented among dementia sufferers. This is probably because women tend to live longer than men and are exposed to greater Alzheimer’s risk through age. There is little to link sex hormone status or hormone replacement therapy to dementia risk.

Mood disorders

Moderate and severe depression can give rise to poor attention, concentration and memory function. This may look like dementia but usually resolves when the depression is successfully treated. It is not clear whether depressive illness alone is a risk factor for Alzheimer’s disease or other forms of dementia.

Head injury

Moderate to severe head injuries resulting in loss of consciousness, particularly if repeated, increases risk of Alzheimer’s disease and dementia. Good advice is to keep using that bike helmet!


A healthy diet is thought to be protective against dementia but the evidence is weak. A ‘heart smart’ diet with low levels of saturated fat and cholesterol, and plenty of antioxidant rich foods, and an adequate intake of vitamin C and E through natural sources is the most protective. Eating oily fish (salmon, tuna, trout, halibut and mackerel among others) or taking supplements of omega 3 fatty acids have a protective influence.


Heavy use of alcohol is a risk factor for dementia. However a small intake of no more than one to two standard drinks a day of alcohol may be protective.


The amount of education may have an influence on the risk of Alzheimer’s disease. Less education seems to be associated with greater risk but this may come about because less educated individuals are more likely to have higher risk factors for vascular disease and therefore dementia. More educated people may have greater brain reserve to protect them against clinical manifestations of dementia when affected by Alzheimer’s disease. More controversial is whether education grows brain cells and connections and protects against dementia.

Mental, social and physical activity

Mental activities, organised social interaction, and active leisure pursuits and purposeful walking (or singing and dancing) reduce the risk of developing dementia.

Marital status

Being married and staying married may confer a reduced risk of Alzheimer’s disease. The message here is to be nice to your partner!


A review of all the factors above will lead to a better informed patient about the risk of dementia. The most important risk factors are age, genes and cardiovascular risk. While the first two are rather resistant to modification, patients can be encouraged to reduce cardiovascular risk factors, improve their diet and participate in exercise and mental and social activities. This should reduce dementia risk.

Prof Philip Morris