Table 3.

Summary of most cited articles reporting on the progression of late onset Alzheimer’s disease. The studies are based in a cohort of persons with late onset Alzheimer’s disease in New York City (PI: Y. Stern)

Study [Ref]	Participants/design	Exposures/outcomes	Findings
N Scarmeas, SM Albert, JJ Manly, Y Stern (2006) Education and rates of cognitive decline in incident Alzheimer’s disease. [5]	During the course of a community-based multiethnic prospective cohort study of individuals aged ≥65 years living in New York, 312 patients were diagnosed with incident AD and were followed overall for 5.6 (up to 13.3) years	The subjects received an average of 3.7 (up to 9) neuropsychological assessments consisting of 12 individual tests. With the aid of a normative sample, a standardized composite cognitive score, as well as individual cognitive domain scores were calculated. GEE models were used to examine the association between education and rates of cognitive decline	Composite cognitive performance declined by 9% of a standard deviation per year. Rates of decline before and after AD incidence were similar. For each additional year of education there was 0.3% standard deviation lower composite cognitive performance for each year of follow-up. The association between higher education and faster decline was noted primarily in the executive-speed (0.6%) and memory (0.5%) cognitive domains and was present over and above age, gender, ethnicity, differential baseline cognitive performance, depression, and vascular comorbidity
N Scarmeas, JA Luchsinger, R Mayeux, Y Stern (2007) Mediterranean diet and Alzheimer’s disease mortality. [12]	A total of 192 community-based individuals in New York who were diagnosed with AD were prospectively followed every 1.5 years	Adherence to the MeDi (0–9 point scale with higher scores indicating higher adherence) was the main predictor of mortality in Cox models that were adjusted for period of recruitment, age, gender, ethnicity, education, APOE genotype, caloric intake, smoking, and BMI	85 AD patients (44%) died during the course of 4.4 (±3.6, 0.2–13.6) years of follow-up. In unadjusted models, higher adherence to MeDi was associated with lower mortality risk (for each additional MeDi point HR 0.79; 95% CI 0.69–0.91; p = 0.001). This result remained significant after controlling for all covariates (0.76; [0.65–0.89]; p = 0.001). In adjusted models, as compared to AD patients at the lowest MeDi adherence tertile, those at the middle tertile had lower mortality risk (0.65; [0.38–1.09]; 1.33 years longer survival), while subjects at the highest tertile had an even lower risk (0.27 [0.10–0.69]; 3.91 years longer survival; p for trend 0.003)
JC Amatniek, WA Hauser, C DelCastillo-Castaneda, DM Jacobs, K Marder, K Bell, M Albert, J Brandt, Y Stern (2006) Incidence and predictors of seizures in patients with Alzheimer’s disease. [11]	Mild AD patients were prospectively followed at 6-month intervals	Estimate incidence of unprovoked seizures, compare age-specific risk of unprovoked seizures with population norms, and identify characteristics at baseline (demographics, duration and severity of AD, physical and diagnostic test findings, and comorbid medical and psychiatric conditions) influencing unprovoked seizure risk. Review of study charts and medical records supplemented coded end-point data	The cumulative incidence of unprovoked seizures at 7 years was nearly 8%. In all age groups, risk was increased compared with a standard population, with an 87-fold increase in the youngest group (age 50–59 years) and more than a threefold increase in the oldest group (age 85 + years). In multivariate modeling, independent predictors of unprovoked seizures were younger age (RR, 0.89 per year increase in age; 95% CI, 0.82–0.97), African-American ethnic background (RR, 7.35; 95% CI, 1.42–37.98), more-severe dementia (RR, 4.15; 95% CI, 1.06–16.27), and focal epileptiform findings on EEG (RR, 73.36; 95% CI, 1.75–3075.25)
EP Helzner, JA Luchsinger, N Scarmeas, S Cosentino, AM Brickman, MM Glymour, Y Stern (2009) Contribution of vascular risk factors to disease progression in Alzheimer’s disease. [6]	156 incident AD patients (mean age 83 years at diagnosis) were prospectively followed every 1.5 years	The exposures were vascular factors including medical history (heart disease, stroke, diabetes, hypertension), smoking, and pre-diagnosis blood lipid measurements (total cholesterol, HDL-C, LDL-C, and triglycerides). The main outcome was change in a composite score of cognitive ability from diagnosis on	In GEE models (adjusted for age, race/ethnicity and education), higher cholesterol (total and LDL-C), and diabetes history were associated with faster cognitive decline. Each 10-unit increase in cholesterol and LDL-C was associated with a 10% of a standard deviation decrease in cognitive score per year of follow-up (p < 0.001 for total cholesterol, p = 0.001 for LDL-C). HDL and triglycerides were not associated with rate of decline. Diabetes history was associated with an additional 50% of a standard deviation decrease in cognitive score per year (p = 0.05). History of heart disease and stroke were associated with cognitive decline among APOE ε4 carriers only. In a final GEE model that included HDL-C, LDL-C, and diabetes, only higher LDL-C was independently associated with faster cognitive decline

AD, Alzheimer’s disease; APOE, apolipoprotein E; BMI, body mass index; GEE, general estimating equation; HDL-C, high density lipoproteins; HR, hazards ratio; LDL-C, low density lipoproteins; MeDi, Mediterranean diet; RR, risk ratio.