Table 1.

Summary of most cited articles of risk factors for late onset Alzheimer’s disease from Columbia University in New York City. These manuscripts were based in the Washington Heights Inwood Columbia Aging Project (WHICAP; PI: R. Mayeux)

Study [Ref]	Participants/design	Exposures/outcomes	Findings
N Scarmeas, Y Stern, MX Tang, R Mayeux, JA Luchsinger (2006) Mediterranean diet and risk of Alzheimer’s disease. [1]	2,258 community-based nondemented individuals aged 65 years and older followed prospectively every 1.5 years	Adherence to the MeDi (0–9 point scale with higher scores indicating higher adherence) was the main predictor in models that were adjusted for cohort, age, gender, ethnicity, education, APOE genotype, caloric intake, smoking, medical comorbidity index, and BMI. The outcome was incident AD	There were 262 incident AD cases during the course of 4 (±3.0, 0.2–13.9) years of follow-up. Higher adherence to the MeDi was associated with lower risk of AD (HR, 0.91, 95% CI, 0.83–0.98; p = 0.015). Compared to subjects in the lowest MeDi tertile, subjects in the middle MeDi tertile had a HR of 0.85 (0.63–1.16) and those at the highest tertile a HR of 0.60 (0.42–0.87) for AD (p for trend 0.007)
N Scarmeas, JA Luchsinger, N Schupf, AM Brickman, S Cosentino, MX Tang, Y Stern (2009) Physical activity, diet and risk of Alzheimer’s disease. [4]	1,880 community-dwelling elders without dementia with both diet and PA information available information available followed prospectively every 1.5 years	Adherence to the MeDi (0–9 scale trichotomized into low-middle-high or dichotomized into low-high) and PA (sum of weekly participation in a variety of physical activities, weighted by the type of activity [light, moderate, vigorous] trichotomized into none-some-much or dichotomized into low-high), separately and combined, were the main predictors in Cox models. Models were adjusted for cohort, age, gender, ethnicity, education, APOE genotype, caloric intake, BMI, smoking, depression, leisure activities, a comorbidity index, and baseline clinical dementia rating. The outcome was AD	A total of 282 incident AD cases occurred during 5.4 (±3.3) years of follow-up. When considered simultaneously, both MeDi adherence (HR for middle 0.98 [0.72–1.33]; HR for high 0.60 [0.42–0.87]; p for trend 0.008) and PA (HR for some 0.75 [0.54–1.04]; HR for much 0.67 [0.47–0.95]; p for trend 0.03) were associated with lower AD risk. As compared with individuals neither adhering to the MeDi nor exercising (low–low; absolute AD risk 19%), those either adhering to the MeDi or exercising (low-high or high-low) had a lower risk (absolute risk 15%, HR 0.73; 0.56–0.95) for developing AD, while those both adhering to the MeDi and exercising (high–high) had an even lower risk (absolute risk 12%, HR 0.56; 0.40–0.78; p for trend <0.001)
N Scarmeas, Y Stern, R Mayeux, JA Luchsinger (2006) Mediterranean diet, Alzheimer’s disease and vascular mediation. [3]	A case-control study nested within WHICAP: 194 AD patients versus 1,790 non-demented	Adherence to the MeDi (0–9 point scale with higher scores indicating higher in logistic regression models that were adjusted for cohort, age, gender, ethnicity, education, APOE genotype, caloric intake, smoking, medical comorbidity index, and BMI. The outcome was AD. Mediation was evaluated by examining the attenuation of the OR with the introduction of vascular variables	Higher adherence to the MeDi was associated with lower risk of AD (OR, 0.76, 95% CI, 0.67–0.87; p < 0.001). Compared to subjects in the lowest MeDi tertile, subjects in the middle MeDi tertile had an OR of 0.47 (0.29–0.76) and those at the highest tertile an OR of 0.32 (0.17–0.59) for AD (p for trend <0.001). Introduction of the vascular variables in the model did not change the magnitude of the association
N Scarmeas, Y Stern, R Mayeux, JJ Manly, N Schupf, JA Luchsinger (2006) Mediterranean diet and mild cognitive impairment. [2]	There were 1,393 cognitively normal participants, 275 of whom developed MCI during 4.5 (±2.7, 0.9–16.4) years of follow-up. There were 482 subjects with MCI, 106 of whom developed AD during 4.3 (±2.7, 1.0–13.8) years of follow-up. Participants were followed every 1.5 years	We used Cox proportional hazards to investigate the association between adherence to the MeDi (0–9 scale; higher scores higher adherence) and (1) incidence of MCI and (2) progression from MCI to AD. All models were adjusted for cohort, age, gender, ethnicity, education, APOE genotype, caloric intake, BMI, and time duration between baseline dietary assessment and baseline diagnosis	Regarding incidence of MCI in cognitively normal subjects, compared to subjects in the lowest MeDi adherence tertile, subjects in the middle MeDi tertile had 17% (HR, 0.83; 95% CI, 0.62–1.12; p = 0.24) less risk of developing MCI, while those at the highest MeDi adherence tertile had 28% (HR, 0.72; 95% CI, 0.52–1.00; p = 0.05) less risk of developing MCI (trend HR, 0.85; 95% CI, 0.72–1.00; p for trend = 0.05). Regarding incidence of AD in subjects with MCI, compared to subjects in the lowest MeDi adherence tertile, subjects in the middle MeDi adherence tertile had 45% (HR, 0.55; 95% CI, 0.34–0.90; p = 0.01) less risk of developing AD, while those at the highest MeDi adherence tertile had 48% (HR, 0.52; 95% CI, 0.30–0.91; p = 0.02) less risk of developing AD (trend HR, 0.71; 95% CI, 0.53–0.95; p for trend = 0.02)

AD, Alzheimer’s disease; APOE, apolipoprotein E; BMI, body mass index; HR, hazards ratio; MCI, mild cognitive impairment; MeDi, Mediterranean diet; OR, odds ratio; PA, physical activity.