Supplementary Material for: Timing of cognitive test score decline prior to incident dementia diagnosis in Blacks and Whites: The Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS)

Introduction: Commonly occurring dementias include those of Alzheimer’s, vascular, and mixtures of these and other pathologies. They are believed to evolve over many years, but that time interval has been difficult to establish. Our objective is to determine how many years in advance of a dementia diagnosis cognitive scores begin to change. Methods: 14,086 dementia-free ARIC participants underwent a cognitive exam at baseline visit 2 (1990-1992, mean age 57±5.72), and in 11,244 at visit 4 (1996-1998), 5,640 at visit 5 (2011-2013), and 3,574 at visit 6 (2016-2017) with surveillance for dementias of all causes combined. Within 5-year intervals after each visit, we compared performance on the Delayed Word Recall Test (DWRT), the Digit Symbol Substitution Test (DSST), the Word Fluency Test (WFT), and the combined mean of three cognitive tests at baseline in participants who were diagnosed with dementia within each interval versus those who survived the interval without a dementia diagnosis. Z-scores were adjusted for demographics and education in separate regression models for each visit. We plotted adjusted z-score means by time interval following each visit. Results: During follow-up 3,334, 2,821, 1,218, and 329 dementia cases were ascertained after visits 2, 4, 5, and 6 respectively. Adjusted DWRT z-scores were significantly lower 20-25 years before dementia than those who did not experience dementia within 25 years. DSST z-scores were significantly lower at 25-30 years and 3-test combination z-scores were significantly lower as early as 30-31 years before onset. The difference between dementia and non-dementia group in the visit 2 3-test combination z-score was -0.20 at 30-31 years prior to dementia diagnosis. As expected, differences between the dementia and non-dementia groups increased closer to the time of dementia occurrence, up to their widest point at 0-5 years prior to dementia diagnosis. The difference between dementia and non-dementia groups in the visit 2 3-test combination z-score was -0.90. WFT z-score differences were smaller than for the DSST or DWRT and began later. Patterns were similar in Black and White participants. Conclusion: DWRT, DSST and combined 3-test z-scores were significantly lower more than 20 years prior to diagnosis in the dementia group versus the non-dementia group. Findings contribute to our knowledge of the long prodromal period in Blacks and Whites

Supplementary Material for: Cognition and Incident Dementia Hospitalization: Results from the Atherosclerosis Risk in Communities Study

<b><i>Background/Aims:</i></b> Cognitive decline is a defining feature of dementia. We sought to determine if a single baseline cognitive test score or change in test score over time is more strongly associated with risk of dementia hospitalization. We also sought to compare short- and long-term dementia risk. <b><i>Methods:</i></b> Prospective cohort study of 9,399 individuals from the Atherosclerosis Risk in Communities Study (median 10 years of follow-up). Cognition was assessed at two time points (6 years apart) using three tests: Delayed Word Recall Test (DWRT), Digit Symbol Substitution Test (DSST), and Word Fluency Test. Dementia hospitalizations were determined using ICD-9 codes. <b><i>Results:</i></b> Baseline cognitive test scores were associated with both short-term and long-term risk of dementia. The association of 6-year change in cognitive test score with dementia risk was stronger than that of individual test scores at a single visit [change from highest to lowest tertile, DWRT: hazard ratio = 6.45 (95% confidence interval = 1.80–23.08); DSST: hazard ratio = 10.94 (95% confidence interval = 3.07–38.97)]. <b><i>Conclusions:</i></b> In this community-based population, 6-year changes in cognitive scores were more strongly associated with risk of incident dementia hospitalization than baseline scores, although single DWRT and DSST scores were predictive. Our findings support the contention that cognitive changes may precede clinical dementia by a decade or more

Supplementary Material for: Occupation, Retirement Age, and 20-Year Cognitive Decline: The Atherosclerosis Risk in Communities Neurocognitive Study

Introduction: We examined the association of both midlife occupation and age at retirement with cognitive decline in the Atherosclerosis Risk in Communities (ARIC) biracial community-based cohort. Methods: Current or most recent occupation at ARIC baseline (1987-89; ages 45-64y) was categorized based on 1980 US census major occupation groups and tertiles of the Nam-Powers-Boyd occupational status score (n=14,090). Retirement status via annual follow-up questionnaires administered ascertained in 1999-2007 was classified as occurring before or after age 70 (n=7,503). Generalized estimating equation models were used to examine associations of occupation and age at retirement with trajectories of global cognitive factor scores, assessed from visit 2 (1990-92) to visit 5 (2011–2013). Models were a priori stratified by race and sex and adjusted for demographics and comorbidities. Results: Low occupational status and blue-collar occupations were associated with low baseline cognitive scores in all race-sex strata. Low occupational status and homemaker status were associated with faster decline in White women but slower decline in Black women compared to high occupational status. Retirement before age 70 was associated with slower cognitive decline in White men and women and in Black men. Results did not change substantially after accounting for attrition. Conclusion: Low occupational status was associated with cognitive decline in women but not in men. Earlier retirement was associated with a slower cognitive decline in White participants and in Black men. Further research should explore reasons for the observed associations and race-sex differences

Supplementary Material for: The Metabolic Syndrome and Cognitive Decline in the Atherosclerosis Risk in Communities Study (ARIC)

<b><i>Background:</i></b> Midlife metabolic syndrome (MetS) may impact cognitive health as a construct independently of hypertension, hyperlipidemia and other components. <b><i>Methods:</i></b> 10,866 participants aged 45-64 years at baseline were assessed for MetS and completed cognitive testing at two later time points (3 and 9 years from the baseline visit). <b><i>Results:</i></b> MetS is associated with increased odds of low cognitive performance in the domains of executive function and word fluency, but not with 6-year cognitive decline. Individual MetS components explained this association (hypertension, diabetes, low HDL, elevated triglycerides and increased waist circumference). <b><i>Conclusions:</i></b> A focus on the individual risk factors as opposed to MetS during midlife is important to reduce the incidence of cognitive impairment in later life

Supplementary Material for: Serum Vitamin D Concentrations and Cognitive Change Over 20 Years: The Atherosclerosis Risk in Communities Neurocognitive Study

<b><i>Background/Aims:</i></b> 25-hydroxyvitamin D (25[OH]D) concentrations have been associated with cognitive decline and incident dementia in elderly populations; however, these relationships are susceptible to reverse causation. Less is known about the association of midlife 25(OH)D with long-term cognitive decline. <b><i>Methods:</i></b> This was a prospective cohort study of 13,044 participants (mean age 57 years at baseline) in the Atherosclerosis Risk in Communities Study. 25(OH)D was measured from serum collected at baseline (1990–1992) using liquid chromatography tandem high-sensitivity mass spectrometry. Cognition was assessed using 3 neuropsychological tests at 3 time points, which were combined into a composite cognitive <i>Z</i>-score. Multivariable-adjusted linear mixed-effects models with random intercepts and slopes were used to estimate associations between 25(OH)D and cognitive change over 20 years. <b><i>Results:</i></b> Compared to persons with sufficient 25(OH)D (≥30 ng/mL), those with deficient (< 20 ng/mL) and intermediate (20–< 30 ng/mL) 25(OH)D concentrations had similar cognitive decline in composite cognitive <i>Z</i>-scores (deficient versus sufficient: –0.035 [95% CI –0.104 to 0.033] and intermediate versus sufficient: –0.029 [95% CI –0.080 to 0.023]). <b><i>Conclusions:</i></b> Lower concentrations of 25(OH)D measured in midlife were not significantly associated with more rapid cognitive decline over a 20-year follow-up period. The results of this prospective study are less susceptible to reverse causation than prior studies