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. 2017 Oct 1;74(10):1246-1254.
doi: 10.1001/jamaneurol.2017.1658.

Associations Between Midlife Vascular Risk Factors and 25-Year Incident Dementia in the Atherosclerosis Risk in Communities (ARIC) Cohort

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Associations Between Midlife Vascular Risk Factors and 25-Year Incident Dementia in the Atherosclerosis Risk in Communities (ARIC) Cohort

Rebecca F Gottesman et al. JAMA Neurol. .
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Importance: Vascular risk factors have been associated with cognitive decline. Midlife exposure to these factors may be most important in conferring late-life risk of cognitive impairment.

Objectives: To examine Atherosclerosis Risk in Communities (ARIC) participants in midlife and to explore associations between midlife vascular risk factors and 25-year dementia incidence.

Design, setting, and participants: This prospective cohort investigation of the Atherosclerosis Risk in Communities (ARIC) Study was conducted from 1987-1989 through 2011-2013. The dates of this analysis were April 2015 through August 2016. The setting was ARIC field centers (Washington County, Maryland; Forsyth County, North Carolina; Jackson, Mississippi; and Minneapolis suburbs, Minnesota). The study comprised 15 744 participants (of whom 27.1% were black and 72.9% white) who were aged 44 to 66 years at baseline.

Main outcomes and measures: Demographic and vascular risk factors were measured at baseline (obesity, smoking, diabetes, prehypertension, hypertension, and hypercholesterolemia) as well as presence of the APOE ε4 genotype. After the baseline visit, participants had 4 additional in-person visits, for a total of 5 in-person visits, hospitalization surveillance, telephone calls, and repeated cognitive evaluations. Most recently, in 2011-2013, through the ARIC Neurocognitive Study (ARIC-NCS), participants underwent a detailed neurocognitive battery, informant interviews, and adjudicated review to define dementia cases. Additional cases were identified through the Telephone Interview for Cognitive Status-Modified or informant interview, for participants not attending the ARIC-NCS visit, or by an International Classification of Diseases, Ninth Revision dementia code during a hospitalization. Fully adjusted Cox proportional hazards regression was used to evaluate associations of baseline vascular and demographic risk factors with dementia.

Results: In total, 1516 cases of dementia (57.0% female and 34.9% black, with a mean [SD] age at visit 1 of 57.4 [5.2] years) were identified among 15 744 participants. Black race (hazard ratio [HR], 1.36; 95% CI, 1.21-1.54), older age (HR, 8.06; 95% CI, 6.69-9.72 for participants aged 60-66 years), lower educational attainment (HR, 1.61; 95% CI, 1.28-2.03 for less than a high school education), and APOE ε4 genotype (HR, 1.98; 95% CI, 1.78-2.21) were associated with increased risk of dementia, as were midlife smoking (HR, 1.41; 95% CI, 1.23-1.61), diabetes (HR, 1.77; 95% CI, 1.53-2.04), prehypertension (HR, 1.31; 95% CI, 1.14-1.51), and hypertension (HR, 1.39; 95% CI, 1.22-1.59). The HR for dementia for diabetes was almost as high as that for APOE ε4 genotype.

Conclusions and relevance: Midlife vascular risk factors are associated with increased risk of dementia in black and white ARIC Study participants. Further studies are needed to evaluate the mechanism of and opportunities for prevention of the cognitive sequelae of these risk factors in midlife.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Gottesman reported being an associate editor for Neurology. Dr Davis reported serving on a data and safety monitoring board for Eli Lilly. Dr Windham reported being an investigator in a clinical trial sponsored by Acadia Pharmaceuticals. Dr Knopman reported serving on a data and safety monitoring board for Lundbeck Pharmaceuticals and for the Dominantly Inherited Alzheimer Network (DIAN) study; reported being an investigator in clinical trials sponsored by Biogen, TauRx Therapeutics, and Eli Lilly; and reported receiving research support from the National Institutes of Health. No other disclosures were reported. No authors were compensated for being coauthors or helping with the adjudication process.


Figure 1.
Figure 1.. Chronology of Atherosclerosis Risk in Communities (ARIC) Study Visits for All Black and White Participants
ARIC-NCS indicates ARIC Neurocognitive Study.
aContinuous surveillance of hospitalizations and deaths; annual telephone calls from study onset through 2012, when the calls were switched to a semiannual schedule. Informant telephone interviews for dementia also began in 2013.
Figure 2.
Figure 2.. Distribution of Dates of Dementia Diagnoses
Darker circles represent dementia cases; lighter circles represent other censored cases (due to either death or dropout). TICSm indicates Telephone Interview for Cognitive Status–Modified.

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