Epidemiologic studies of modifiable factors associated with cognition and dementia: systematic review and meta-analysis

Abstract

BackgroundCognitive impairment, including dementia, is a major health concern with the increasing aging population. Preventive measures to delay cognitive decline are of utmost importance. Alzheimer’s disease (AD) is the most frequent cause of dementia, increasing in prevalence from <1% below the age of 60 years to >40% above 85 years of age.MethodsWe systematically reviewed selected modifiable factors such as education, smoking, alcohol, physical activity, caffeine, antioxidants, homocysteine (Hcy), n-3 fatty acids that were studied in relation to various cognitive health outcomes, including incident AD. We searched MEDLINE for published literature (January 1990 through October 2012), including cross-sectional and cohort studies (sample sizes > 300). Analyses compared study finding consistency across factors, study designs and study-level characteristics. Selecting studies of incident AD, our meta-analysis estimated pooled risk ratios (RR), population attributable risk percent (PAR%) and assessed publication bias.ResultsIn total, 247 studies were retrieved for systematic review. Consistency analysis for each risk factor suggested positive findings ranging from ~38.9% for caffeine to ~89% for physical activity. Education also had a significantly higher propensity for “a positive finding” compared to caffeine, smoking and antioxidant-related studies. Meta-analysis of 31 studies with incident AD yielded pooled RR for low education (RR = 1.99; 95% CI: 1.30-3.04), high Hcy (RR = 1.93; 95% CI: 1.50-2.49), and current/ever smoking status (RR = 1.37; 95% CI: 1.23-1.52) while indicating protective effects of higher physical activity and n-3 fatty acids. Estimated PAR% were particularly high for physical activity (PAR% = 31.9; 95% CI: 22.7-41.2) and smoking (PAR%=31.09%; 95% CI: 17.9-44.3). Overall, no significant publication bias was found.ConclusionsHigher Hcy levels, lower educational attainment, and decreased physical activity were particularly strong predictors of incident AD. Further studies are needed to support other potential modifiable protective factors, such as caffeine.

Cognitive correlates of cerebrospinal fluid biomarkers for Alzheimer’s disease

“…These findings are consistent with previous community studies showing an association between odour identification scores and decline on a general cognitive functioning measure [12,36]. The reason that we only found an association with the MMSE may be explained by the fact that the MMSE does not have a floor effect in mild-moderate dementia and is perhaps less vulnerable to practice effects as opposed to cognitive tests.…”

“…Also, in our study no association between CSF markers and semantic memory was found, but these results were just above threshold of statistical significance. In addition, we found that the association between CSF markers and memory performance was similar across diagnostic groups, while other studies reported that some of the associations between CSF markers and memory performance were observed in specific diagnostic groups only [15,36,37]. These differences may be explained by the statistical approach.…”

“…However, since the sample size was small (no intake n=25, mild to moderate intake n=28) this finding needs further replication. Protective effects against cognitive decline have been found for mild to moderate alcohol consumption, but these findings are somewhat controversial and further research is needed to confirm this [11,[36][37][38].…”

Normative data of the Brazilian elderly in Logical Memory subtest of WMS-R

“…Angel, Fay, Bouazzaoui, Baudouin, and Isingrini (2010) refer to the interaction between age and education in performing a wordlist recalling task, in which adults with lower levels of education performed poorly when compared with those with higher levels of formal education. Although it is expected that some cognitive skills decline with age, some changes are clearly associated with education (Beydoun et al, 2014). Foss, Formigheri and Speciali (2009), for example, find significant positive correlations between level of education and performance in VEM tests in the elderly.…”

Exploratory study of sublimed sulfur, in cognitively normal subjects and in Alzheimer’s dementia (AD) subjects: implications for Sulfur targeting Hydrogen sulfide (H2S)/Homocysteine (Hcy) and beta-galactosidase (GALAC)/Autophagy Signaling in AD

“…The emerging role of homocysteine in predicting cognitive decline independent of cardiovascular risks has drawn equal attention in the context of cognitive aging and AD [12][13][14][15][16][17]. In the seminal Framingham study recruiting 1092 normal healthy subjects (677 female and 425 male; mean age: 76 years) were followed for 8 years for repeated plasma Hcy monitoring [13].…”