Kucharska‐Newton, Anna

Background: Vascular aging is associated with cognitive decline. Aortic stiffness is a hallmark of vascular aging. We tested the hypothesis that greater aortic stiffness is associated with a faster rate of cognitive decline over 5 years among older adults. Methods: A prospective cohort study at the 5th (2011-2013) and 6th (2016-2017) examinations of the Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS) was conducted to quantify the association between baseline aortic stiffness and cognitive decline over 5 years. A total of 4639 participants (mean age: 75 years, 41% men, 22% Black) with baseline measures of aortic stiffness and cognitive function were included in the analysis. Aortic stiffness was measured as carotid-femoral pulse wave velocity (cfPWV) using the Omron VP-1000 Plus device and analyzed continuously per 1 standard deviation meter/second (3.20 m/s). Elevated aortic stiffness was defined as the upper 25th percentile of cfPWV (13.39 m/s). Cognitive function was based on ten neuropsychological tests across multiple domains of cognition, including memory, executive function/processing speed, and language. A global cognitive performance factor score was estimated based on all cognitive tests at both visits. Multivariable linear regression was used to examine the associations of each standard deviation (SD) increment in cfPWV and elevated cfPWV with annual cognitive decline over 5 years. Interactions with baseline cognitive status were assessed. To account for attrition (35% over 5 years), multiple imputation by chained equations was used to impute missing global cognitive performance factor scores at visit 6. Results: Each 1 SD increase in cfPWV was associated with 0.008 SD (Beta (β)=-0.008, 95% confidence interval (CI): -0.010, -0.003) annual rate of decline in cognitive function after adjustment for age, sex, education, race-center and ApoE4. With additional adjustment for ever smoking, total weekly physical activity time, mean arterial pressure, diabetes, and body mass index, each SD higher cfPWV was associated with 0.005 SD (β=-0.005, 95% CI: -0.010, -0.001) annual rate of decline in cognitive function. Elevated cfPWV was associated with 0.015 SD (β=-0.015, 95% CI: -0.024, -0.005) annual decline in cognitive function, and with 0.010 SD (β=-0.010, 95% CI: -0.020, 0.0001) annual decline after additional adjustment. Conclusion: Higher aortic stiffness is associated with the rate of decline in global cognitive function among community-dwelling older adults. The hemodynamic sequelae of aortic stiffening may contribute to cognitive decline among older adults.

Background Changes in white matter microstructural integrity are detectable before appearance of white matter lesions on magnetic resonance imaging as a manifestation of cerebral small‐vessel disease. The information relating poor white matter microstructural integrity to aortic stiffness, a hallmark of aging, is limited. We aimed to examine the association between aortic stiffness and white matter microstructural integrity among older adults. Methods and Results We conducted a cross‐sectional study to examine the association between aortic stiffness and white matter microstructural integrity among 1484 men and women (mean age, 76 years) at the 2011 to 2013 examination of the ARIC‐NCS (Atherosclerosis Risk in Communities Neurocognitive Study). Aortic stiffness was measured as carotid‐femoral pulse wave velocity. Cerebral white matter microstructural integrity was measured as fractional anisotropy and mean diffusivity using diffusion tensor imaging. Multivariable linear regression was used to examine the associations of carotid‐femoral pulse wave velocity with fractional anisotropy and mean diffusivity of the overall cerebrum and at regions of interest. Each 1‐m/s higher carotid‐femoral pulse wave velocity was associated with lower overall fractional anisotropy (β=−0.03; 95% CI , −0.05 to −0.02) and higher overall mean diffusivity (β=0.03; 95% CI , 0.02–0.04). High carotid‐femoral pulse wave velocity (upper 25th percentile) was associated with lower fractional anisotropy (β=−0.40; 95% CI , −0.61 to −0.20) and higher overall mean diffusivity (β=0.27; 95% CI , 0.10–0.43). Similar associations were observed at individual regions of interest. Conclusions High aortic stiffness is associated with low cerebral white matter microstructural integrity among older adults. Aortic stiffness may serve as a target for the prevention of poor cerebral white matter microstructural integrity.

Introduction: Stiffening of the aorta is associated with greater pulse pressure and transmission of pulsatile energy into the cerebral circulation, which can increase susceptibility to microvascular damage in the brain. We tested the hypothesis that higher aortic stiffness measured in late-life is associated with a greater prevalence odds of dementia measured ~5 years later. Methods: Dementia-free ARIC-NCS participants (n=4753; mean age: 75 years; 42% male; 21% black) with measures of aortic stiffness at the visit 5 (2011-2013) examination were included. Aortic stiffness was measured by carotid-femoral pulse wave velocity (cfPWV) using the VP-1000 Plus device (Omron Co., Japan) and modeled as continuous (per standard deviation (SD)), categorical into distribution-based quartiles, and as elevated vs. non-elevated cfPWV according to the upper 25 th percentile (13.34 m/s). Cognitive status (normal/mild cognitive impairment (MCI)/dementia) was ascertained at the visit 5 and 6 (2016-2017) examinations with expert review by an adjudication committee of in-person cognitive testing. A multivariable logistic regression model estimated the adjusted association of cfPWV with 5-year odds of dementia. Results: Among dementia-free participants, a 1 SD higher cfPWV was associated with a greater odds of dementia (Odds Ratio (OR): 1.19 (95% Confidence Interval (CI): 1.03, 1.39). Elevated cfPWV (upper 25 th percentile) was also associated with a greater odds of dementia (OR: 1.54, 95% CI: 1.08, 2.19) in this sample. This association was stronger among participants who were cognitively normal at visit 5 (n=3758, Table): the multivariable-adjusted OR of dementia = 2.16 (95% CI: 1.35, 3.47) for elevated vs. non-elevated cfPWV. The risk of dementia among those with baseline MCI (n=955) was not associated with cfPWV levels. Results were robust to adjustment for vascular risk factors. Conclusions: Among older adults, especially when MCI is not present, greater central aortic stiffness is associated with dementia risk.

Background Central arterial stiffening and increased pulsatility, with consequent cerebral hypoperfusion, may result in structural brain damage and cognitive impairment. Methods and Results We analyzed a cross‐sectional sample of ARIC ‐ NCS (Atherosclerosis Risk in Communities–Neurocognitive Study) participants (aged 67–90 years, 60% women) with measures of cognition (n=3703) and brain magnetic resonance imaging (n=1255). Central arterial hemodynamics were assessed as carotid‐femoral pulse wave velocity and pressure pulsatility (central pulse pressure). We derived factor scores for cognitive domains. Brain magnetic resonance imaging using 3‐Tesla scanners quantified lacunar infarcts; cerebral microbleeds; and volumes of white matter hyperintensities, total brain, and the Alzheimer disease signature region. We used logistic regression, adjusted for demographics, apolipoprotein E ɛ4, heart rate, mean arterial pressure, and select cardiovascular risk factors, to estimate the odds of lacunar infarcts or cerebral microbleeds. Linear regression, additionally adjusted for intracranial volume, estimated the difference in log‐transformed volumes of white matter hyperintensities , total brain, and the Alzheimer disease signature region. We estimated the mean difference in cognitive factor scores across quartiles of carotid‐femoral pulse wave velocity or central pulse pressure using linear regression. Compared with participants in the lowest carotid‐femoral pulse wave velocity quartile, participants in the highest quartile of carotid‐femoral pulse wave velocity had a greater burden of white matter hyperintensities ( P =0.007 for trend), smaller total brain volumes (−18.30 cm 3 ; 95% CI , −27.54 to −9.07 cm 3 ), and smaller Alzheimer disease signature region volumes (−1.48 cm 3 ; 95% CI , −2.27 to −0.68 cm 3 ). These participants also had lower scores in executive function/processing speed (β=−0.04 z score; 95% CI , −0.07 to −0.01 z score) and general cognition (β=−0.09 z score; 95% CI , −0.15 to −0.03 z score). Similar results were observed for central pulse pressure . Conclusions Central arterial hemodynamics were associated with structural brain damage and poorer cognitive performance among older adults.

Objectives To examine the association between hospitalization, critical illness, and infection occurring during middle‐ and late‐life and structural brain abnormalities in older adults. Design Prospective cohort study. Setting Atherosclerosis Risk in Communities (ARIC) Study. Participants A community sample of adults who were 44 to 66 years of age at study baseline. Measurements Active surveillance of local hospitals and annual participant contact were used to gather hospitalization information (including International Classification of Diseases, Ninth Revision , codes) on all participants over a 24‐year surveillance period. Subsequently, a subset of participants underwent 3‐Tesla brain magnetic resonance imaging (MRI) to quantify total and regional brain volumes, white matter hyperintensity (WMH) volume, and white matter microstructural integrity (fractional anisotropy (FA) and mean diffusivity (MD) as measured using diffusion tensor imaging (DTI)). Results Of the 1,689 participants included (mean age at MRI 76±5), 72% were hospitalized, 14% had a major infection, and 4% had a critical illness during the surveillance period. Using covariate‐adjusted regression, hospitalization was associated with 0.12–standard deviation (SD) greater WMH volume (95% confidence interval (CI)=0.00–0.24) and poorer white matter microstructural integrity (0.17‐SD lower FA, 95% CI=–0.27 to –0.06; 0.16‐SD greater MD, 95% CI=0.07–0.25) than no hospitalization. There was a dose‐dependent relationship between number of hospitalizations, smaller brain volumes, and lower white matter integrity ( p ‐trends ≤.048). In hospitalized participants, critical illness was associated with smaller Alzheimer's disease (AD) signature region (–1.64 cm 3 , 95% CI=–3.16 to –0.12); major infection was associated with smaller AD signature region (–1.28 cm 3 , 95% CI=–2.21 to –0.35) and larger ventricular volume (3.79 cm 3 , 95% CI= 0.81–6.77). Conclusions Whereas all‐cause hospitalization was primarily associated with lower white matter integrity, critical illness and major infection were associated with smaller brain volume, particularly within regions implicated in AD.

Background Prior studies have demonstrated a link between the metabolic syndrome and increased risk of cardiovascular mortality. Whether the metabolic syndrome is associated with sudden cardiac death is uncertain. Methods and Results We characterized the relationship between sudden cardiac death and metabolic syndrome status among participants of the ARIC (Atherosclerosis Risk in Communities) Study (1987–2012) free of prevalent coronary heart disease or heart failure. Among 13 168 participants, 357 (2.7%) sudden cardiac deaths occurred during a median follow‐up of 23.6 years. Participants with the metabolic syndrome (n=4444) had a higher cumulative incidence of sudden cardiac death than those without it (n=8724) (4.1% versus 2.3%, P <0.001). After adjustment for participant demographics and clinical factors other than components of the metabolic syndrome, the metabolic syndrome was independently associated with sudden cardiac death (hazard ratio, 1.70, 95% confidence interval, 1.37–2.12, P <0.001). This relationship was not modified by sex (interaction P =0.10) or race (interaction P =0.62) and was mediated by the metabolic syndrome criteria components. The risk of sudden cardiac death varied according to the number of metabolic syndrome components (hazard ratio 1.31 per additional component of the metabolic syndrome, 95% confidence interval, 1.19–1.44, P <0.001). Of the 5 components, elevated blood pressure, impaired fasting glucose, and low high‐density lipoprotein were independently associated with sudden cardiac death. Conclusions We observed that the metabolic syndrome was associated with a significantly increased risk of sudden cardiac death irrespective of sex or race. The risk of sudden cardiac death was proportional to the number of metabolic syndrome components.

Background Atrial fibrillation ( AF ) is associated with increased risk of hospitalization. Little is known about the impact of AF on utilization of noninpatient health care or about sex or race differences in AF ‐related utilization. We examined rates of inpatient and outpatient utilization by AF status in the Atherosclerosis Risk in Communities study. Methods and Results Participants with incident AF enrolled in fee‐for‐service Medicare for at least 12 continuous months between 1991 and 2009 (n=932) were matched on age, sex, race and field center with up to 3 participants without AF (n=2729). Healthcare utilization was ascertained from Medicare claims and classified by primary International Classification of Diseases, ninth revision code. The average annual numbers of days hospitalized were 13.2 (95% CI 11.6 to 15.0) and 2.8 (95% CI 2.5 to 3.1) for those with and without AF , respectively. The corresponding numbers of annual outpatient claims were 53.3 (95% CI 50.5 to 56.3) and 22.9 (95% CI 22.1 to 23.8) for those with and without AF , respectively. Most utilization among AF patients was attributable to non‐ AF conditions. The adjusted rate ratio for annual days hospitalized for other cardiovascular disease–related reasons was 4.58 (95% CI : 3.41 to 6.16) for those with AF versus those without AF . The association between AF and healthcare utilization was similar among men and women and among white and black participants. Conclusions Participants with AF had considerably greater healthcare utilization, and the difference in utilization for other cardiovascular disease –related reasons was substantial. In addition to rate or rhythm treatment, AF management should focus on the accompanying cardiovascular comorbidities.

We examined the association of variation in the type 2 diabetes risk-conferringTCF7L2gene with the risk of incident coronary heart disease (CHD) among the lean, overweight, and obese members of the Atherosclerosis Risk in Communities (ARIC) Study cohort. Cox proportional hazard regression analyses were performed using a general model, with the major homozygote as the reference category. For 9,865 whites, a significant increase in the risk of CHD was seen only among lean (BMI<25 kg/m2) individuals homozygous for theTallele of theTCF7L2rs7903146 gene risk variant (hazard ratio 1.42; 95% CI 1.03,1.97;P=.01). No association was found among 3,631 blacks, regardless of BMI status. An attenuated hazard ratio was observed among the nondiabetic ARIC cohort members. This study suggests that body mass modifies the association of theTCF7L2rs7903146 T allele with CHD risk.