EFFECTS OF CEREBROVASCULAR INFARCT BURDEN ON COGNITIVE DECLINE IN THE PRESENCE OF DEMENTIA AND DEATH: ACCOUNTING FOR POTENTIALLY INFORMATIVE DROPOUT USING COMPETING RISK SHARED PARAMETER MODELS: THE ARIC STUDY

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.

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Association of lung function with cognitive decline and dementia: the Atherosclerosis Risk in Communities (ARIC) Study

European Journal of Neurology ◽

10.1111/j.1468-1331.2010.03340.x ◽

2011 ◽

Vol 18 (6) ◽

pp. 888-898 ◽

Cited By ~ 44

Author(s):

S. S. Pathan ◽

R. F. Gottesman ◽

T. H. Mosley ◽

D. S. Knopman ◽

A. R. Sharrett ◽

...

Keyword(s):

Lung Function ◽

Cognitive Decline ◽

Atherosclerosis Risk In Communities ◽

Atherosclerosis Risk ◽

Aric Study

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4489 Association between surgery with general anesthesia and cognitive decline in older adults: analysis using shared parameter models for informative dropout

Journal of Clinical and Translational Science ◽

10.1017/cts.2020.168 ◽

2020 ◽

Vol 4 (s1) ◽

pp. 45-45

Author(s):

Phillip Schulte ◽

Katrina Devick ◽

Juraj Sprung

Keyword(s):

Older Adults ◽

Cognitive Decline ◽

Mixed Effects ◽

Cognitive Outcomes ◽

Drop Out ◽

Mixed Effects Models ◽

Z Score ◽

Informative Dropout ◽

Linear Mixed Effects Models ◽

Linear Mixed Effects

OBJECTIVES/GOALS: Recent studies have assessed the association between surgery with general anesthesia and cognitive decline in longitudinal cohorts of older adults. Patients diagnosed with dementia more frequently drop out of these longitudinal studies or are unable to complete the test battery. We revisit this aim with focus on methods for informative dropout. METHODS/STUDY POPULATION: We use data from the Mayo Clinic Study of Aging (MCSA), a longitudinal epidemiological study of the prevalence, incidence, and risk factors for mild cognitive impairment (MCI) and dementia. Our primary outcome of interest was global cognitive z-score, assessed at study visits every 15 months. We implement linear mixed effects models to assess the association between post-enrollment exposure to surgery/anesthesia and subsequent cognitive decline trajectories. Demented patients more frequently drop out of MCSA, so, subjects with the worst cognitive outcomes are unobserved and missing data may be informative. Since this missingness may be missing not at random, we use shared parameter models to analyze continuous cognitive outcomes while jointly modeling time to dementia. RESULTS/ANTICIPATED RESULTS: A total 1948 subjects, non-demented at baseline, from the MCSA were included. Median age was 79, 51% of subjects were male, and 16% had MCI at enrollment. Among median follow-up of 4 study visits over median 5.4 years, 172 patients developed dementia and dropped out from further assessments of cognitive function. In adjusted linear mixed effects models, our data suggest post-enrollment exposure to surgery/anesthesia is associated with a decline in cognitive function over time (change in slope = −0.07 standard deviations of cognitive z-score per year, 95%CI = −0.08, −0.05, p<.001). After adjusting for informative dropout using shared parameter models, surgery/anesthesia is associated with greater cognitive decline (change in slope = −0.14 per year, 95%CI = −0.16, −0.12, p<.001). DISCUSSION/SIGNIFICANCE OF IMPACT: We revisited a prior analysis by our group with consideration of informative dropout. Subjects who dropout due to dementia may have different trajectories of cognitive decline compared to non-demented subjects. Shared parameter models estimate the association between surgery/anesthesia and cognitive decline accounting for informative dropout.

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Cognitive Decline and Oral Health in Middle-aged Adults in the ARIC Study

Journal of Dental Research ◽

10.1177/0022034513497960 ◽

2013 ◽

Vol 92 (9) ◽

pp. 795-801 ◽

Cited By ~ 44

Author(s):

S. Naorungroj ◽

G.D. Slade ◽

J.D. Beck ◽

T.H. Mosley ◽

R.F. Gottesman ◽

...

Keyword(s):

Oral Health ◽

Cognitive Decline ◽

Middle Aged ◽

Middle Aged Adults ◽

Aric Study

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Obstructive Sleep Apnea and 15-Year Cognitive Decline: The Atherosclerosis Risk in Communities (ARIC) Study

SLEEP ◽

10.5665/sleep.5434 ◽

2016 ◽

Vol 39 (2) ◽

pp. 309-316 ◽

Cited By ~ 24

Author(s):

Pamela L. Lutsey ◽

Lindsay G.S. Bengtson ◽

Naresh M. Punjabi ◽

Eyal Shahar ◽

Thomas H. Mosley ◽

...

Keyword(s):

Obstructive Sleep Apnea ◽

Sleep Apnea ◽

Cognitive Decline ◽

Atherosclerosis Risk In Communities ◽

Obstructive Sleep ◽

Atherosclerosis Risk ◽

Aric Study

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RELATIONSHIPS OF VERY SMALL, INFARCT-LIKE LESIONS WITH 20-YEAR COGNITIVE DECLINE: THE ARIC STUDY

Alzheimer s & Dementia ◽

10.1016/j.jalz.2017.07.083 ◽

2017 ◽

Vol 13 (7) ◽

pp. P211

Author(s):

B.Gwen Windham ◽

Steven R. Wilkening ◽

Jonathan V. Tingle ◽

Laura Coker ◽

David S. Knopman ◽

...

Keyword(s):

Cognitive Decline ◽

Aric Study ◽

Small Infarct

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Abstract 28: Orthostatic Hypotension is Associated With 20-year Cognitive Decline and Incident Dementia: the Atherosclerosis Risk in Communities (ARIC) Study

Circulation ◽

10.1161/circ.135.suppl_1.28 ◽

2017 ◽

Vol 135 (suppl_1) ◽

Author(s):

Andreea Rawlings ◽

Stephen Juraschek ◽

Gerardo Heiss ◽

Timothy Hughes ◽

Michelle Meyer ◽

...

Keyword(s):

Cognitive Decline ◽

Orthostatic Hypotension ◽

Cox Regression ◽

Underlying Disease ◽

P Value ◽

Atherosclerosis Risk In Communities ◽

Incident Dementia ◽

History Of ◽

Aric Study

Background: Orthostatic hypotension (OH) has been associated with incident cardiovascular disease and all-cause mortality, but few studies have examined long-term associations with cognitive decline and dementia Hypothesis: OH will be associated with greater cognitive decline and risk of incident dementia Methods: We prospectively analyzed 11503 participants who attended visit 1 (1987-1989) of the ARIC study and had no history of coronary heart disease or stroke. OH was defined as a drop in systolic blood pressure (BP) >=20 mmHg or a drop in diastolic BP >=10 mmHg upon standing from a supine position. Dementia was ascertained using cohort surveillance, telephone contact with the participant or their proxy, or a comprehensive cognitive and neurologic exam in 2011-2013. Cognition was measured via three neuropsychological tests administered in 1990-1992, 1996-1998, and 2011-2013 that were summarized using a Z score. We used adjusted Cox regression and linear mixed models. Results: At visit 1 (mean age 54 years, 57% female, 27% black) 6% of participants had OH. In adjusted models, persons with OH at baseline were 40% more likely to develop dementia than those without OH (HR: 1.40, 95%CI: 1.13, 1.73; Table). Associations were significantly larger in persons with hypertension (p-value for interaction=0.023). Persons with OH compared to those without had significantly more cognitive decline over 20 years (difference: -0.12, 95% CI: -0.23, -0.02; Table). Conclusions: OH assessed in midlife was independently associated with incident dementia and cognitive decline over 20 years. Although typically considered a transient mechanism, these data suggest that OH, or the underlying disease conditions manifesting as OH, persist over time. Whether OH is a marker of vulnerability beyond that of standard hypertension measures, or whether repeated transient exposure to hypotension reduces perfusion to the brain sufficiently to lead to long-term cerebral dysfunction is an important area for further research.

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Milk Intake at Midlife and Cognitive Decline over 20 Years. The Atherosclerosis Risk in Communities (ARIC) Study

Nutrients ◽

10.3390/nu9101134 ◽

2017 ◽

Vol 9 (10) ◽

pp. 1134 ◽

Cited By ~ 8

Author(s):

Natalia Petruski-Ivleva ◽

Anna Kucharska-Newton ◽

Priya Palta ◽

David Couper ◽

Katie Meyer ◽

...

Keyword(s):

Cognitive Decline ◽

Milk Intake ◽

Atherosclerosis Risk In Communities ◽

Atherosclerosis Risk ◽

Aric Study

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Periodontitis and Risk of Diabetes in the Atherosclerosis Risk In Communities (ARIC) Study: A BMI-modified Association

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgab337 ◽

2021 ◽

Author(s):

Shaoping Zhang ◽

Kamaira H Philips ◽

Kevin Moss ◽

Di Wu ◽

Hamdi S Adam ◽

...

Keyword(s):

Periodontal Disease ◽

Risk Model ◽

Continuous Variable ◽

Competing Risk ◽

Incident Diabetes ◽

Disease Stage ◽

Atherosclerosis Risk In Communities ◽

Biological Variables ◽

Atherosclerosis Risk ◽

Aric Study

Abstract Purpose To determine whether periodontal disease is positively associated with incident diabetes across the continuum of body mass levels (BMI) and test the hypothesis that the periodontal risk for incident diabetes is modified by BMI. Methods We included 5569 diabetes-free participants from Visit 4 (1996-1998) of the Atherosclerosis Risk in Communities (ARIC) Study and followed them until 2018. Periodontal disease status was classified by periodontal profile class (PPC)-Stages and incident diabetes was based on participant report of physician diagnosis. We estimated the hazard ratios (HR) for diabetes using a competing risk model for each PPC-Stage. We assessed multiplicative interactions between periodontal disease and BMI (as a continuous variable) on risk of diabetes. Results During a median time of 19.4 years of follow-up, 1,348 incident diabetes cases and 1,529 deaths occurred. Compared to “healthy/incidental disease” Stage , participants with PPC-“severe periodontal disease” or “severe tooth loss” Stage and lower BMI had elevated risk for diabetes adjusting for demographic, smoking, education and biological variables when accounting for death as a competing risk with HRs 1.76 (95%CI 1.10-2.80) and 2.11 (95% CI 1.46-3.04), respectively. The interaction between PPC-stages and BMI was significant (p= 0.01). No significant associations of PPC-Stages with incident diabetes were present when BMI was above 31 kg/m 2. Conclusion Periodontal disease was associated with incident diabetes, especially in non-obese participants. Dentists should be aware that periodontal disease is associated with incident diabetes but the association may be modified for patient’s at higher BMI levels.

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