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Potentially Modifiable Risk Factors in the Development of Alzheimer’s Disease
and dementia suggest that education is strongly linked with early life Table 1: Summary of Studies Investigating Potential
circumstances (e.g. socioeconomic status), motivational ability or
Risk Factors for Alzheimer’s Disease
health behaviour (e.g. nutrition and physical activity).
Potential Risk Factor Significant No Review or Example
Association Significant Meta- Studies
Pre-morbid Intelligence
Found Association analysis
Two studies using a more direct measure of pre-morbid intelligence
Found
found a significant association between performance in cognitive Cognitive Ability
tests and risk of AD or dementia. In one study, a measure of verbal
Educational level 11 4 9, 45 7, 8
intelligence (which is considered to provide a good estimate of pre-
Pre-morbid IQ 2 0 11, 12
morbid intelligence) applied at baseline was a better predictor of
Cognitive activity 6 1 46 13
Occupational 2 4 45 14
incident dementia four years later than was educational level.
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attainment
Another study in which several memory and intelligence tests were
Motivational Ability
applied at baseline found that lower memory function predicted
Conscientiousness 1 0 19
higher risk of dementia 22 years later.
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Emotional Health
Depression 5 6 20 21
Cognitive Activity
Neuroticism 3 0 22
Seven studies were identified that investigated the relation between
Physical Activity 12 4 46 23, 24
participation in cognitive activities (e.g. reading books and newspapers,
Social Activity
writing, studying, doing crossword puzzles) in mid- to late life and risk of
Social activity 4 0 46 25
AD and dementia. Almost all (six) studies found a reduced risk of AD in
Social network 4 0 46 26
individuals who frequently engaged in cognitive activities (e.g. relative
Vascular Risk Factors
risk 0.4, 95% CI 0.2–0.7), even when the APOE 4 allele was controlled.
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Diabetes 6 5 27 28
Hypertension 5 6 27 29
Occupational Attainment Hypercholesterol 2 2 27 30
Occupational activities may provide a source of continued cognitive
Obesity 1 4 27 31
stimulation, contributing to the development of cognitive reserve. Nutrition
Five of the six longitudinal studies identified used a two-category
Homocysteine 3 1 6, 40 33
variable of occupational attainment, e.g. low level (unskilled, semi-
Vitamin B
6
1 2 6, 40 34
skilled) versus high level (self-employed, professional, skilled). Only
Vitamin B
12
0 4 6, 40 34
Folate 5 1 6, 40 34
two of these five studies found that people who worked in low-skilled
Vitamin E 3 4 6, 40 35
occupations had a higher risk of AD or dementia (e.g. relative risk 2.3,
Vitamin C 1 5 6, 40 35
95% CI 1.3–3.8).
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A different approach is to rate each occupation in
Flavonoids 0 3 6, 40 35
terms of the complexity of work with data, people and things. One
Beta-carotene 0 5 6, 40 35
longitudinal study found a decreased risk of all-cause dementia, but
Polyunsaturated fat 3 1 6, 40 36
not AD, in people who have worked in occupations characterised by Diverse diet 2 0 6, 40 37, 38
high complexity of work with people and things.
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Fish 2 1 6, 40 39
In sum, lower cognitive ability seems to be a risk factor for AD and a more specific link to the development of AD.
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We are currently
dementia in general. Results differ depending on the measurement conducting longitudinal studies to investigate this relationship, partly in
approach. Although educational level, pre-morbid intelligence and co-operation with the German Competence Network on Dementia.
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cognitive activities are clearly linked to AD and any-cause dementia,
findings for occupational attainment are less conclusive, presumably Conscientiousness – one component of the five-factor model of
because this variable depends not only on cognitive ability, but also personality – is a related construct that can be defined as the
on motivational, social and other abilities.
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tendency to control impulses and to be goal-directed. Whereas
motivational ability is assumed to be modifiable through training,
Motivational Ability conscientiousness is thought to be a stable personality trait. One
The concept of brain reserve is more comprehensive than that of longitudinal study found that relative risk of AD is slightly lower in
cognitive reserve. Brain reserve enables the brain to tolerate highly conscientious individuals, even after adjusting for numerous
neuropathological dementia-related changes without clinical control variables (relative risk 0.97, 95% CI 0.93–0.997).
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manifestation. In the case of behavioural brain reserve,
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behavioural
and mental training throughout life is assumed to promote the more Emotional Health
efficient use of brain networks and compensation of disrupted A recent meta-analysis on the association of depression and risk of
networks. We have suggested that not only pre-morbid cognitive ability AD identified 11 longitudinal studies.
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Only half (five) of these studies
but also pre-morbid motivational ability contributes to brain reserve.
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found that the risk of AD was significantly higher in individuals who
We hypothesise that people with strong motivational abilities (e.g. reported depressive symptoms earlier in life.
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The mean risk in this
decision regulation, activation regulation, motivation regulation and meta-analysis was 1.9 (95% CI 1.6–2.3), suggesting that there is a link
self-efficacy) have a lower risk of AD. Epidemiological research has between depression and risk of AD. Depression often accompanies
shown that motivational ability is associated with some mental and early dementia and may therefore be an early prodrome of dementia
physical disorders and risk factors for AD (e.g. depressive symptoms, rather than an independent risk factor for AD. However, findings show
educational and occupational attainment, physical activity), suggesting that the interval between diagnoses of depression and AD is positively
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