Alzheimer’s Disease (AD) is the most common cause of dementia. While the hunt for effective treatment and the elusive “cure” for AD continues, there is some evidence that simple lifestyle measures may be effective in delaying the onset of dementia.
Population-based studies looking at risk factors for AD have identified numerous associations and some of these are potentially modifiable. Long-term studies to show lower rates of dementia as an effect of risk factor reduction have not yet been completed, but nevertheless, it seems reasonable to recommend these “brain protective” strategies to older patients in order to potentially delay the onset of AD. In addition, most of these recommendations improve other aspects of health as well. According to a recent review in the Lancet, about a third of AD cases may be blamed on modifiable risk factors and it is deduced that controlling risk factors at the correct age may reduce the future prevalence of AD. (Norton et al 2014)
The pathological hallmark of AD is the abnormal accumulation of protein deposits consisting of amyloid and tau protein. Drugs that remove amyloid do not improve the symptoms so these may be late markers of the disease and not the cause. Abnormal inflammation and oxidation are also present and this pathogenic mechanism is implicated in many other diseases, notably cardiovascular disease. This has lead to the oft-quoted maxim “if it is good for the heart, it is good for the head”.
Genetic factors cannot be modified but are only part of the risk. Familial Alzheimer’s is very rare: less than 3% of cases. Early onset AD starts before the age of 65 and is more likely to have an inherited basis. Late onset AD has been linked to the APOE4 allele. This allele does not cause AD but does increase the risk of AD. It is a controversial test as it is not diagnostic if positive- many patients will not get AD- and does not exclude AD if negative. Most dementia societies do not advocate for the use of this test. However some have argued that the presence of the allele may act as a motivation to lead a “brain protective” lifestyle.
There is substantial evidence that lifestyle is a significant factor in the development of AD. A well known study comparing African-American populations in Indianapolis in the USA to the Yoruba people in Ibadan in Nigeria, showed a significantly higher incidence of AD in the urban Indianapolis community despite similar ethnic origins. (Hendrie et al 1995)
Problems that are consistently associated with an increased risk of AD include: diabetes, midlife hypertension, midlife obesity, physical inactivity, depression, smoking and low education.
Entire books have been written about all aspects of this highly emotive topic and this is by no means a comprehensive review.
A Mediterranean diet high in antioxidants can be recommended. Low to moderate alcohol intake (1 unit per day for women and 2 units for men) is protective but heavy intake is harmful. Coffee- up to 3 cups a day- may have a protective effect. Many patients will ask about unproven nutritional therapies such as coconut oil, co-enzyme Q10, coral calcium and ginko biloba among others. They will often want to take them despite the lack of scientific evidence based on their own beliefs. Many of these compounds are not regulated in terms of purity and can be expensive. Sometimes they can be harmful in terms of drug-food interactions or side effects so check these before allowing patients to use them. Increased dietary fish or omega 3 fatty acid intake has shown benefit in observational studies and this may be due to the effects on vascular disease. Resveratrol might be one of the beneficial compounds in red wine and it exists as a supplement but studies of this compound are not yet conclusive.
In general high doses of individual vitamins do not seem to be beneficial (and some may be harmful) unless there is a vitamin deficiency. A multivitamin can be recommended in patients with poor nutritional status and can be allowed if patients wish to take one. Vitamin D intake of 800IU-1000IU daily is recommended for older adults although certain risk groups (e.g. those who are osteoporotic, institutionalized, exposed to limited light, taking vitamin D-interfering medications, malnourished or frail) may require higher doses and measuring levels of 25OH Vitamin D may aid with determining dosage. This is a costly test and supplementation is very inexpensive so if the suspicion is high then empiric treatment may be warranted depending on the scenario.
Certain medications are associated with worsening cognitive function. There are many resources available that list these including the Beer’s List. (AGS 2012)
The commonest culprits would be anticholinergics, antipsychotics, benzodiazepines (and related compounds) and H2 receptor blockers.
Blood pressure treatment has not been shown to specifically reduce the risk of dementia but has been shown to reduce heart failure, stroke and mortality. The ideal blood pressure changes according to your age and stage of life. Tighter control in middle age (<140/<90) is beneficial whereas in the elderly the goals differ (<150/<90). Blood pressure should always be measured lying and standing (as orthostasis is very common) and the goals applied to standing blood pressure. Isolated systolic hypertension is a frequent finding in the elderly and keeping the diastolic BP above 60-65mmHg is recommended regardless of the systolic value achieved. Overzealous treatment of hypertension may reduce cerebral perfusion and conversely worsen cognition. This is a general guide and these goals should always be individualized as patients with co-morbid diseases may benefit from lower or higher targets.
The management of diabetes should be tailored to the patient. Frail or cognitively impaired patients or those with co-morbidities such as renal or cardiac disease or longstanding complicated diabetes may be more at risk of hypoglycaemia than hyperglycaemia. Fit, community-dwelling patients with a life expectancy of over 10 years should be treated according to the same guidelines as younger patients.
Untreated atrial fibrillation results in poor cerebral perfusion and an increased risk of stroke. Anticoagulation is underutilized in the elderly due to perceived increased risk of bleeding that is often overestimated. There are numerous guidelines outlining the management and preferred strategy to treat this common condition.
High LDL cholesterol and low HDL is associated with dementia although fat is essential for brain to function. The current role of statins for dementia prevention is confusing for clinicians and patients alike. Statins have been shown to prevent dementia (even non-vascular dementia) in several large studies but may worsen cognition transiently in other patients. In general I recommend statins to patients who require them for other reasons such as secondary prevention or those who meet criteria for primary prevention.
OSA is an important cause of cognitive impairment and increased cardiovascular risk in the elderly. Elderly patients may have this condition without the typical obese phenotype and collateral information regarding sleep patterns is important.
Inadequate brain oxygenation via reduced PO2 or Hb levels is an obvious but overlooked correctable cause of cognitive impairment.
TSH screening in asymptomatic patients is controversial but as symptoms of thyroid dysfunction are non-specific many older patients would warrant this test. Treatment is usually done ‘slower and lower” than in the younger populations. Treating subclinical hypothyroidism if the TSH is <10mIU/l does not seem to have cognitive benefits and may be associated with risks- consult guidelines for details.
Vitamin B12 deficiency can contribute to cognitive and other neurological disease. Higher levels may be desirable in patients with cognitive impairment and we supplement those patients with levels of <300pmol/L.
Multiple risk factor reduction is additive- many of these risk factors have already been outlined.
This is mandatory.
Screening for depression is important and many simple tools such as the Geriatric Depression Scale exist. Depressed older adults are far more likely to develop AD. This may be due to neuropathophysiological changes, reduced cognitive reserve in depression and earlier unmasking of AD or the increasing recognition that depression can even represent an early stage of AD. Depression may also influence other risk factors such as socializing, physical exercise and eating habits causing additive harm.
Staying socially engaged reduces the risk of AD. Having a “purpose in life” is associated with better cognitive outcomes.
Higher education reduces the risk of AD. Later in life, stimulating mental activities are also beneficial, and can compensate for lower education. These activities should be enjoyable and challenging rather than a strain. Cognitive training, provided it is enjoyable is not harmful.
Exercise is one of the most beneficial strategies to slow or prevent dementia and may even increase brain volume. Recommendations are to exercise several times a week even for as little as 15 minutes a day or 90 minutes a week. Most of the research studied walking but it seems reasonable to extrapolate that any exercise that increases blood flow would be sufficient. Strength training also shown to be of benefit. Exercise also improves sleep and mood and can be incorporated into a daily routine. The assistance of a physiotherapist or biokineticist to design an individualised program is a good idea. Head injuries increase the risk of dementia and should be avoided when considering an exercise regimen.
Not enough evidence: NSAIDS and hormonal therapy among others.
Myths about AD: dental fillings, flu vaccines, aluminium pots and aspartame among many, many others.
In short: exercise, a healthy diet, mental stimulation, social engagement and stress reduction are key components.