An Attempt to Quantify the Degree to Which Alzheimer's is a Lifestyle Disease
To what degree is Alzheimer's disease a consequence of poor lifestyle choices such as being sedentary and overweight, as is largely the case for type 2 diabetes, versus a consequence of the unavoidable accumulation of cell and tissue damage that causes degenerative aging? Researchers here run the numbers to obtain a partial answer. You'll note a couple of interesting associations such as with low body mass index (BMI) in later life, as considerable loss of weight in old age is usually a sign of systematic health issues, and the fact that people with cancer tend not to get Alzheimer's, an phenomenon noted in recent years, but which as of yet has no full explanation.
Age-standardized prevalence of Alzheimer's disease (AD) for those aged ≥60 years varied in a narrow band, 5-7% in most world regions. AD accounts for approximately 60% of dementia incidence. Over the past 100+ years, researchers have never stopped to investigate the pathogenic mechanisms, prevention and therapy for AD. However, we had currently no effective drugs for this disease. Hence, it is increasingly attracting people's attentions to figure out how to prevent its occurrence. In the preventative perspective, Alzheimer's risk factors can be roughly categorized into two types: unmodifiable factors and modifiable factors. The former majorly refers to genetic underpinnings, aging and sex (female), et al.; and the latter comprises seven domains, including pre-existing physical disease, lifestyle, occupation, clinical drugs/therapy, blood biochemistry, diet, and mental psychology, which are exactly the potential targets for preventative strategies.The team spent about one year in database searching, paper screening, data collecting and analyzing. Finally, 323 eligible papers in which 93 modifiable factors were identified were selected from roughly 17,000 literatures. The study found the significant associations of 36 factors categorized into six domains (including drugs, diet, biochemistry, mental health, lifestyle and pre-existing disease) with Alzheimer's occurrence. The most significant risk factor is heavy smoking while the most significant protective factor is healthy diet, for example the Mediterranean diet. Furthermore, we graded the evidence strength of meta-analysis for each factor based on two major domains: pooled sample size and the heterogeneity of each analysis. We found 11 risk factor with grade I evidence strength, including heavy smoking, low diastolic blood pressure, high BMI in midlife, carotid atherosclerosis, type 2 diabetes in Asian population, low BMI, low educational attainment, high total homocystein level, depression, systolic blood pressure more than 160 mmHg and frailty.
Among these risk factors, a total of 9 risk factors (including obesity in mid-life, current smoking in Asian population, carotid atherosclerosis, type 2 diabetes in Asian population, low educational attainment, high total homocysteine level, depression, high systolic blood pressure ≥160 mmHg, and frailty) for which global prevalence was accessible were selected for calculating population attributable risk (PAR). The combined PAR% indicated that these nine potentially modifiable risk factors were associated with up to roughly 66% of AD cases globally. Additionally, our study also found grade I evidence for 18 protective factors, including coffee/caffeine drinking, high folate intake, cognitive activity, high vitamin E intake, high vitamin C intake, current statin use, arthritis, light-to-moderate drinking, ever alcohol use, ever use of estrogens, anti-hypertensive medications, NASIDs use, high BMI in late-life, high Aβ42/40 ratio and some pre-existing diseases including arthritis, heart disease, metabolic syndrome, and cancer.