Abstract 47: Subclinical Atherosclerosis and 20-Year Cognitive Decline: The Atherosclerosis Risk in Communities (ARIC) Neurocognitive Study

Circulation ◽  
2015 ◽  
Vol 131 (suppl_1) ◽  
Author(s):  
Shelly-Ann M Love ◽  
Priya Palta ◽  
Corey A Kalbaugh ◽  
A.Richey Sharrett ◽  
Alden L Gross ◽  
...  

Introduction: Cardiovascular risk factors are reportedly predictive of cognitive decline and dementia but the association between the extent and severity of subclinical atherosclerosis with cognitive decline remains understudied. Hypothesis: The systemic burden of atherosclerosis measured non-invasively is associated with the rate of decline in domain-specific (memory, executive function and language) and global cognition from mid-life to late life. Methods: Members of the ARIC cohort (N=12313; 58% women, 24% African American (AA), 76% white) aged 46-70 years at their 1990-1992 examination were followed through 2011-2013. Participants with prevalent stroke, myocardial infarction or coronary heart disease were excluded. Atherosclerosis at baseline (n=5217) was assessed by carotid artery b-mode ultrasound (presence and number of plaques, bilaterally) and by ankle-brachial index <0.9 measured with an oscillometric device. Tests of memory (Delayed Word Recall Test), executive function (Digit Symbol Substitution Test), and language (Word Fluency Test) were administered in 1990-92, 1996-98 and 2011-13. Test-specific z scores were calculated at each exam based on the means and standard deviations at baseline. A global cognition z score was estimated by averaging the 3 test-specific z scores and standardizing to baseline. Race-stratified linear random effects regression was used to estimate the association between subclinical atherosclerosis and 20-year declines in domain-specific cognition and global cognition. We adjusted for age, sex and level of education. Inverse probability weighting (IPW) was used to limit bias due to attrition. Results: In AA, the presence of carotid plaque and/or ABI <0.90 (n=490) was associated with a lower memory z score (Beta=-0.10, 95% confidence interval, CI: -0.18, -0.02), a lower language z score (Beta=-0.07, 95% CI: -0.14,-0.002) and a lower global cognition z score at baseline (Beta=-0.09, 95% CI: -0.16, -0.02), but not with rates of change in any cognitive score. Among whites at baseline, individuals with subclinical atherosclerosis (n=4099) exhibited lower executive function (Beta=-0.05, 95% CI: -0.08, -0.02) and global cognition (Beta=-0.04, 95% CI: -0.07, -0.01). White participants with subclinical atherosclerosis had a greater 20-year rate of decline in global cognition (Beta=-0.06, 95% CI: -0.10, -0.00) compared to those without subclinical atherosclerosis. Conclusions: Baseline memory, language, and global cognition in AA and executive function and global cognition in whites were lower among those with non-invasively ascertained atherosclerosis compared to those without, independent of covariates in the model. Among whites, subclinical clinical measures of atherosclerosis in mid-life may be indicative of modest, but measurable declines in cognition after additional adjustment for potential bias due to attrition.

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Katherine Samaras ◽  
Steve Makkar ◽  
John D Crawford ◽  
Nicole A Kochan ◽  
Wei Wen ◽  
...  

Abstract Background Metformin use in diabetes has been associated with both increased and decreased dementia rates in observational studies of people with diabetes. Objective: To examine changes in global cognition and specific cognitive domains over 6 years in older adults with diabetes treated with metformin, compared to other glucose lowering medications, and to people without diabetes. Methods Data were examined from the Sydney Memory and Ageing Study, a prospective observational study of 6 years duration of 1037 non-demented community-dwelling elderly aged 70-90 at baseline, derived from a compulsory electoral roll. Neuropsychological testing was performed every 2 years with domain measures of memory, executive function, language, visuospatial function, attention and processing speed and a composite of global cognition. Data were analysed by linear mixed modelling, including age, sex, education, body mass index, heart disease, diabetes, hypertension, stroke, smoking and apolipoprotein E ε4 carriage as covariates. Results: At baseline, 123 participants had diabetes (DM) with 67 receiving metformin (DM+MF) who were similar in demographics to those not receiving metformin (DM-noMF) and those without diabetes (no-DM). Participants with diabetes had higher BMI, lower HDL- and LDL-cholesterol and more prevalent heart disease, hypertension and smoking, compared to no-DM. Over 6-years, DM+MF participants had significantly slower rates of decline in global cognition and executive function, compared to DM-noMF, adjusted for covariates. The rate of decline for each cognitive domain was similar between DM+MF and controls. No impact was found in analyses examining interactions with sex, ApoEε4 carriage or hyperlipidemia. No difference was found in the rate of decline in brain volumes between the groups over 2 years. Incident dementia was significantly higher in DM-noMF, compared to DM+MF (adjusted OR 5.29 [95% CI 1.17-23.88], p,0.05), whereas risk of incident dementia was similar between DM+MF and participants without diabetes. Conclusions: In older people with diabetes receiving metformin, rates of cognitive decline and dementia were similar to that found in people without diabetes and significantly less than that found in people with diabetes not receiving metformin. Large randomized studies in people with and without diabetes are required to determine whether these associations can be attributed to metformin alone or if other factors explain these observations. Future studies will clarify if this cheap and safe medication can be repurposed for prevention of cognitive decline in older people.


Circulation ◽  
2017 ◽  
Vol 135 (suppl_1) ◽  
Author(s):  
Priya Palta ◽  
Honglei Chen ◽  
Jennifer A Deal ◽  
David Knopman ◽  
Michael Griswold ◽  
...  

Introduction: Impairment in the sense of smell is associated with plaques and tangles in the olfactory region of the brain, which connects to the hippocampus where neuropathologic changes related to mild cognitive impairment (MCI) and dementia due to Alzheimer’s disease are first sited. Olfactory impairments may thus be a marker for poor cognitive function and MCI. We assessed olfaction and cognitive function in 6055 White and Black men and women aged 60-99 years. Methods: Sense of smell was measured in ARIC-NCS participants (2011-2013) by the 12-item Sniffin’ Sticks screening test (score range: 0-12, median: 10). A clinically validated threshold (smell score <6) defined olfactory impairment (OI). A multidimensional neuropsychological assessment (10 tests) ascertained performance in domains of memory, language, executive function/processing speed, and global cognition. For relative comparisons across the tests, raw cognitive test scores were standardized to z scores and averaged to yield domain scores. Following review of neuropsychological assessments, medical history, cerebral magnetic resonance imaging, and physical examinations, MCI was classified by a neurologist and neuropsychologist, and adjudicated by a third reviewer. Multivariable linear regression estimated the mean difference in domain-specific z scores among participants with and without OI. Logistic regression was used to quantify the prevalence odds of MCI in participants with vs. those without OI. Models were adjusted for age, sex, race, education, ARIC study center, hypertension, diabetes, smoking, and ApoE4. Race and sex were explored as effect modifiers. Results: The participants’ mean age was 76 years; 41% were male and 23% Black. The prevalence of olfactory impairment was 14%. Compared to participants with no OI, those with OI had a statistically significantly lower mean z score across all cognitive domains [memory: Beta= -0.37 (95% confidence interval [CI]: -0.45, -0.30); language: Beta= -0.39 (95% CI: -0.46, -0.33); executive function/processing speed: Beta= -0.24 (95% CI: -0.32, -0.17); global cognition: Beta= -0.34 (95% CI: -0.41, -0.26). Effect modification by race was observed in the domain of language. Blacks with OI had a greater mean difference in language z score compared to Blacks without OI (Beta= -0.57 (95% CI: -0.70, -0.44)). OI was associated with MCI in Whites, but not Blacks: white participants with OI had greater odds of MCI (Odds Ratio [OR] =1.76, 95% CI: 1.40, 2.21). Sex did not modify these associations. Conclusions: Compared to average cognitive aging (annual rate of decline of 0.04-0.05 standard deviation units/year) relatively large differences in standardized cognitive domain scores are observed between those with and without olfactory impairment among older adults. An impaired sense of smell may serve as a readily accessible early marker of neurodegeneration.


Neurology ◽  
2022 ◽  
pp. 10.1212/WNL.0000000000013174
Author(s):  
Nan Huo ◽  
Prashanthi Vemuri ◽  
Jonathan Graff-Radford ◽  
Jeremy Syrjanen ◽  
Mary Machulda ◽  
...  

Background and Objectives:The prevalence of mid-life cardiovascular conditions and risk factors are higher in men than women. Associations between mid-life cardiovascular conditions or risk factors and mid-life cognitive decline has been reported, but few studies have assessed sex differences in these associations.Methods:We included 1,857 participants enrolled in the population-based Mayo Clinic Study of Aging who were aged 50-69 years at baseline. Participants were evaluated every 15 months by a coordinator, neurologic evaluation, and neuropsychological testing. The neuropsychological testing used nine tests to calculate global cognitive and domain-specific (memory, language, executive function, and visuospatial skills) z-scores. Nurse abstractors reviewed participant medical records to determine the presence of cardiovascular conditions (coronary heart disease, arrhythmias, congestive heart failure) and risk factors (hypertension, diabetes, dyslipidemia, obesity, ever smoking). Linear mixed-effect models evaluated the association between baseline cardiovascular conditions or risk factors and global and domain-specific cognitive decline. Multivariable models adjusted for demographics, APOE genotype, depression, and other medical conditions. Interactions between sex and each cardiovascular condition or risk factor were examined, and results were stratified by sex.Results:Overall, 1,465 (70.3%) participants had at least one cardiovascular condition or risk factor; the proportion of men was higher than women (767 (83.4%) vs 698 (74.5%), p<0.0001). Cross-sectionally, coronary heart disease and ever smoking were associated with a lower visuospatial z-score in multivariable models. Longitudinally, several cardiovascular conditions and risk factors were associated with declines in global and/or domain-specific z scores, but not visuospatial z-scores. Most cardiovascular conditions were more strongly associated with cognition among women: coronary heart disease, and other cardiovascular conditions were associated with global cognition decline only in women (all p<0.05). Additionally, diabetes, dyslipidemia, and coronary heart disease were associated with language z-score decline only in women (all p<0.05). However, congestive heart failure was associated with language z-score decline only in men (all p<0.05).Conclusions:Mid-life cardiovascular conditions and risk factors are associated with mid-life cognitive decline. Moreover, specific cardiovascular conditions and risk factors have stronger associations with cognition decline in mid-life for women than men despite the higher prevalence of those conditions in men.


2020 ◽  
Vol 26 (10) ◽  
pp. 1143-1152
Author(s):  
Ithamar Ganmore ◽  
Isak Elkayam ◽  
Ramit Ravona-Springer ◽  
Hung-Mo Lin ◽  
Xiaoyu Liu ◽  
...  

Objective: Type 2 diabetes (T2D) is associated with motor impairments and a higher dementia risk. The relationships of motor decline with cognitive decline in T2D older adults has rarely been studied. Using data from the Israel Diabetes and Cognitive Decline study (N = 892), we examined associations of decline in motor function with cognitive decline over a 54-month period. Methods: Motor function measures were strength (handgrip) and gait speed (time to walk 3 m). Participants completed a neuropsychologic battery of 13 tests transformed into z-scores, summarized into 4 cognitive domains: episodic memory, attention/working memory, executive functions, and language/semantic categorization. The average of the 4 domains’ z-scores defined global cognition. Motor and cognitive functions were assessed in 18-months intervals. A random coefficients model delineated longitudinal relationships of cognitive decline with baseline and change from baseline in motor function, adjusting for sociodemographic, cardiovascular, and T2D-related covariates. Results: Slower baseline gait speed levels were significantly associated with more rapid decline in global cognition ( P = .004), language/semantic categorization ( P = .006) and episodic memory ( P = .029). Greater decline over time in gait speed was associated with an accelerated rate of decline in global cognition ( P = .050), attention/working memory ( P = .047) and language/semantic categorization ( P<.001). Baseline strength levels were not associated with cognitive decline but the rate of declining strength was associated with an accelerated decline in executive functions ( P = .025) and language/semantic categorization ( P = .006). Conclusion: In T2D older adults, the rate of decline in motor function, beyond baseline levels, was associated with accelerated cognitive decline, suggesting that cognitive and motor decline share common neuropathologic mechanisms in T2D. Abbreviations: HbA1c = hemoglobin A1c; IDCD = Israel Diabetes and Cognitive Decline; T2D = type 2 diabetes


Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Deborah A Levine ◽  
Alden L Gross ◽  
Emily M Briceño ◽  
Nicholas Tilton ◽  
Mohammed U Kabeto ◽  
...  

Background: Sex differences in dementia risk are unclear but some have found greater risk for women. We hypothesized that women have greater cognitive decline than men, after adjusting for potential confounders. Objective: Determine associations between sex and cognitive decline. Methods: We pooled data from 19,378 participants free of stroke and dementia (mean [SD] age 59.8 [10.4] years at first cognitive assessment), of whom 8,654 (44.7%) were men and 3,852 (19.9%) were black, from 5 longitudinal cohorts between 1971 and 2017: Atherosclerosis Risk in Communities Study, Coronary Artery Risk Development in Young Adults Study, Cardiovascular Health Study, Framingham Offspring Study, and Northern Manhattan Study. The primary outcome was change in global cognition. Secondary outcomes were change in memory and executive function. Linear mixed-effects models measured changes in each continuous cognitive outcome over time by sex, adjusted for demographics, education, vascular risk factors, and age*follow-up time, race*follow-up time, systolic blood pressure*follow-up time, and use of antihypertensive medication*follow-up time interaction terms. Cognitive outcomes were set to a t-score metric (mean 50, standard deviation [SD] 10) at a participant’s first cognitive assessment; a 1-point difference represents a 0.1 SD difference in the distribution of cognition across the 5 cohorts. Median follow-up was 12.4 (IQR: 5.9, 21.0) years. Results: Women had significantly higher baseline performance than men in global cognition, executive function, and memory (adjusted differences in intercepts, 2.09 to 2.15 points; all P<0.001) ( Figure ). Compared with men, women had significantly faster declines in global cognition, executive function, and memory (adjusted differences in slopes, 0.04 to 0.06 points per year faster; P <0.001) ( Figure ). Conclusion: These results are consistent with women having greater cognitive reserve but faster cognitive decline than men.


2020 ◽  
Vol 111 (6) ◽  
pp. 1252-1258
Author(s):  
Danni Li ◽  
Jeffrey R Misialek ◽  
Ma Jing ◽  
Michael Y Tsai ◽  
John H Eckfeldt ◽  
...  

Abstract Background Very-long-chain SFAs (VLSFAs) have recently gained considerable attention as having beneficial effects on health and aging. Objectives The objective of this study was to assess the associations of plasma phospholipid VLSFAs [arachidic acid (20:0), behenic acid (22:0), tricosanoic acid (23:0), and lignoceric acid (24:0)] with 20-y cognitive decline in the Atherosclerosis Risk in Communities (ARIC) participants. Furthermore, this study compared the associations of plasma phospholipid VLSFAs with 5 common groups of fatty acids [i.e., total SFAs, total MUFAs, total ω-3 (n–3) PUFAs, total marine-derived ω-3 PUFAs, total ω-6 PUFAs]. Methods This study used a cohort study design of 3229 ARIC participants enrolled at the Minnesota field center. Fatty acids were measured at visit 1 (1987–1989); and cognition was assessed at visits 2 (1990–1992), 4 (1996–1998), and 5 (2011–2013) using 3 tests: the Delayed Word Recall Test (DWRT), the Digit-Symbol Substitution Test (DSST), and the Word Fluency Test (WFT). Results Higher proportions of plasma phospholipid total VLSFAs and each individual VLSFA were associated with less decline in WFT, a test of verbal fluency. For example, 1 SD higher in total VLSFAs at baseline was associated with 0.057 SD (95% CI: 0.018, 0.096, P = 0.004) less cognitive decline over 20 y as measured by WFT score. None of the 5 common fatty acid groups were associated with change in WFT, but a higher proportion of plasma phospholipid total MUFAs was associated with greater decline in DWRT; higher total ω-6 PUFAs with less decline in DWRT; and higher total ω-3 and total marine-derived ω-3 PUFAs with less decline in DSST. Conclusions This study suggests that higher proportions of plasma phospholipid VLSFAs in midlife may be associated with less 20-y cognitive decline.


2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 162-162
Author(s):  
Jessie VanSwearingen ◽  
Mark Redfern ◽  
Ervin Sejdic ◽  
Andrea Rosso ◽  
Anisha Suri

Abstract Community mobility involves walking with physical and cognitive challenges. In older adults (N=116; results here from initial analyses: N=29, Age=75±5 years, 51% females), we assessed gait speed and smoothness (harmonic-ratio) while walking on even and uneven surfaces, with or without an alternate alphabeting dual-task (ABC). ANOVA assessed surface and dual-task effects; Pearson correlations compared gait with global cognition and executive function composite z-scores. The four conditions (even, uneven, even-ABC and uneven-ABC) affected speed(m/s) (0.97±0.14 vs 0.90±0.15 vs 0.83±0.17 vs 0.79±0.16). Smoothness (2.19±0.48 vs 1.89±0.38 vs 1.92±0.53 vs 1.7±0.43) was affected by only surface (controlled for speed). Greater speed was associated with better global cognition(ρ=0.47 to 0.49, p&lt;0.05) for all conditions and with better executive function for even-ABC(ρ=0.39, p=0.04) and uneven-ABC(ρ=0.40, p=0.03). Executive function was associated with smoothness during even(ρp=-0.42, p=0.03) and uneven(ρp=-0.39, p=0.04) walking. Type of walking challenge differentially affects gait quality and associations with cognitive function.


Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Jennifer L Dearborn ◽  
David Knopman ◽  
Richey Sharrett ◽  
Andrea L Schneider ◽  
Clifford Jack ◽  
...  

Background: Midlife obesity is associated with dementia in later life, but how the metabolic syndrome (MetS) relates to cognitive change is less understood. We hypothesized that MetS would be more predictive of 6-year cognitive decline than its individual components in a large biethnic cohort (the ARIC study) and that combinations of risk factors would further increase likelihood of change. Methods: The MetS was defined in 1987-89 on 10,687 participants with two cognitive assessments at two time points. In subjects aged 44 to 66, obesity measures included body mass index (BMI) and waist-to-hip ratio (WTHR). The main outcome measure was change in 1990-92 to 96-99 of three cognitive tests: Delayed Word Recall (DWR), Digit Symbol Substitution Test (DSST), and Word Fluency Test (WFT). Linear and logistic regressions were all adjusted for age, combined race-center, sex, education, smoking, drinking, coronary artery disease and prior stroke. Change was measured as the difference divided by the number of years between visits. Results: At baseline, the prevalence of MetS was 22% (mean age 54 years, 27% black, 55% female, and 28% BMI>30 kg/m2). Subjects with MetS performed in the lowest test quintile (adjusted ORs: DWR 1.3 95% CI 1.1-1.4) in 1996-99, and much of this effect size was explained by an elevated WTHR (DWR OR 1.3 CI 1.1-1.5) and diabetes (DWR OR 1.4 CI 1.2-1.7). MetS was not associated with annual cognitive change, and diabetes was the only significant component associated with change (adjusted beta: DWR 0.03 p=.01, DSST 0.2 p<.001, WFT 0.09 p=.01). Conclusion: MetS at ages 44 to 66 was associated with worse cognitive function at follow-up, but not with annual cognitive decline over several years. Elevated WTHR and diabetes explained most of the association of MetS with cognitive function measures, and diabetes with cognitive decline. Until we have a definition of the MetS more based on pathophysiology, the components of the MetS should be the focus of analysis in future studies.


2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 32-32
Author(s):  
Xiaoran Liu ◽  
Klodian Dhana ◽  
Jeremy Furtado ◽  
Puja Agarwal ◽  
Neelum Aggarwal ◽  
...  

Abstract Objectives There is emerging evidence linking fruit and vegetable consumption and cognitive function. However, mechanistic evidence underlying this relationship is lacking. We aim to examine the association between plasma carotenoids and cognition in a population at risk for cognitive decline. Methods The Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) trial (R01 AG052583) is an ongoing randomized controlled intervention on the effects of the MIND diet in preventing cognitive decline. The primary outcome is global cognition assessed using a battery of 12 cognitive tests. Plasma carotenoid levels were measured in 295 participants. Multivariate linear regression models were used to examine the association between blood nutrients and global and domain-specific cognition. Model was adjusted for age, sex, education, study site, smoking status, and frequency of cognitive and physical activities. The Benjamini-Hochberg method with a false discovery rate of 0.25 was used for multiple testing. Results Participants are predominantly Caucasian females (68%) with obesity (BMI 33.6) and a mean age of 69.8 years. High plasma α-carotene was associated with higher average scores for a global measure of cognition. Individuals in the highest tertile of plasma α-carotene levels (tertile median: 155.8 mcg/L) had a higher average score of 0.17 for global cognition compared to those in the lowest tertile (tertile median: 34.9 mcg/L, P = 0.002). Individuals with high plasma α-carotene levels had a dietary pattern that featured high consumption of vegetables other than green leafy vegetables (i.e., carrots, corn, beets, green beans, and onions), and fruits, as well as, lower consumption of butter, margarine, and fried foods. Plasma levels of α-carotene (p for trend 0.007) and lutein plus zeaxanthin (p for trend 0.009) were also associated with higher mean scores for semantic memory. Conclusions Higher circulating levels of specific forms of carotenoids i.e., α-carotene, lutein plus zeaxanthin was associated with higher scores of global and domain-specific cognitive function in a US population at risk for cognitive decline. Funding Sources Funding: R01 AG052583


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