Diabetes, disability, and dementia risk: Results from the Hispanic Established Populations for the Epidemiologic Studies of the Elderly (H-EPESE)

Background: Emerging research has elucidated pathophysiological relationships among diabetes, disability, cognitive impairment, and incident dementia. However, the relationships between diabetes, disability, and dementia have been largely underexamined in Latino populations, which have a disproportionate prevalence of diabetes and its complications. Aims: This study examines diabetes as a risk factor for subsequent disability and dementia risk in a Mexican-origin older adult sample. Methods: The data are drawn from eight waves (1993–2013) of the Hispanic Established Populations for the Epidemiologic Study of the Elderly (HEPESE; N = 3,050, mean age at baseline = 73.6 (±6.8)). Respondents’ diabetes status at baseline was ascertained by self-report. Disability was assessed using eight functional domains assessed through the Lawton Instrumental Activities of Daily Living (IADL) Scale. Dementia risk was assessed using a Mini-Mental Status Exam (MMSE) score below 18 and the need for aid with at least two IADLs. We used multivariable Cox proportional hazards models to predict the relation between diabetes and time to disability, cognitive impairment, and incident dementia, adjusting for age at migration, socioeconomic status, acculturation, and health status. Results: At baseline, diabetes prevalence was 28.1%, and 37.7% had IADL disability. Diabetes was associated with a higher risk of developing dementia (Hazard Ratio (HR) = 1.22, p < .001) over the approximetely 20 year study period. In addition, immigrants who migrated at age 50 or older had a higher dementia risk (HR = 1.35, p = .01) when compared to their US-born counterpart. Conclusion: Our results highlight the importance of better characterizing the role of diabetes and nativity in the co-occurrence of disability and dementia risk.

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Diabetes, Disability, and Dementia Risk: Results From the HEPESE

Innovation in Aging ◽

10.1093/geroni/igaa057.1906 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

pp. 574-574

Author(s):

Elizabeth Vasquez ◽

Meghana Gadgil ◽

Weihu Zhang ◽

Jacqueline L Angel

Keyword(s):

Older Adults ◽

Proportional Hazards ◽

Oldest Old ◽

Epidemiologic Study ◽

The Elderly ◽

Cox Proportional Hazards ◽

Mexican Origin ◽

Foreign Born ◽

Dementia Risk ◽

Diabetes Status

Abstract The relationship between cognitive function, diabetes and disability among the oldest-old remains largely unexplored, particularly in the Latino population. This study examines dementia risk and diabetes status in a Mexican-origin older adult sample. The data are drawn from eight waves (1993 -2013) of the Hispanic Established Populations for the Epidemiologic Study of the Elderly (HEPESE; N=3,039, mean age at baseline=73.6 (±6.8)). We use multivariable Cox proportional hazards models to predict the relation between diabetes and time to incident dementia (MMSE<24, 1+ IADL), with risk adjustment for age of migration, socioeconomic status, acculturation, and health. Diabetes prevalence at baseline was 27.8 %. Diabetes was associated with a higher risk of developing dementia (HR)=1.22, p<0.001). Foreign-born older adults who migrated at ages 20- 49 had a higher survival probability of being dementia-free (HR=0.84, p=0.001). Our results further highlight the importance of evaluating differences in the cognitive outcomes of Mexican origin older adults.

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Bi-directional association between epilepsy and dementia

Neurology ◽

10.1212/wnl.0000000000011077 ◽

2020 ◽

Vol 95 (24) ◽

pp. e3241-e3247 ◽

Cited By ~ 1

Author(s):

Maria Stefanidou ◽

Alexa S. Beiser ◽

Jayandra Jung Himali ◽

Teng J. Peng ◽

Orrin Devinsky ◽

...

Keyword(s):

Proportional Hazards ◽

Secondary Analysis ◽

Cox Proportional Hazards ◽

Dementia Risk ◽

Incident Dementia ◽

Heart Study ◽

Allele Status ◽

Ε4 Allele ◽

Nested Case Control

ObjectiveTo assess the risk of incident epilepsy among participants with prevalent dementia and the risk of incident dementia among participants with prevalent epilepsy in the Framingham Heart Study (FHS).MethodsWe analyzed prospectively collected data in the Original and Offspring FHS cohorts. To determine the risk of developing epilepsy among participants with dementia and the risk of developing dementia among participants with epilepsy, we used separate, nested, case–control designs and matched each case to 3 age-, sex- and FHS cohort–matched controls. We used Cox proportional hazards regression analysis, adjusting for sex and age. In secondary analysis, we investigated the role of education level and APOE ε4 allele status in modifying the association between epilepsy and dementia.ResultsA total of 4,906 participants had information on epilepsy and dementia and dementia follow-up after age 65. Among 660 participants with dementia and 1,980 dementia-free controls, there were 58 incident epilepsy cases during follow-up. Analysis comparing epilepsy risk among dementia cases vs controls yielded a hazard ratio (HR) of 1.82 (95% confidence interval 1.05–3.16, p = 0.034). Among 43 participants with epilepsy and 129 epilepsy-free controls, there were 51 incident dementia cases. Analysis comparing dementia risk among epilepsy cases vs controls yielded a HR of 1.99 (1.11–3.57, p = 0.021). In this group, among participants with any post–high school education, prevalent epilepsy was associated with a nearly 5-fold risk for developing dementia (HR 4.67 [1.82–12.01], p = 0.001) compared to controls of the same educational attainment.ConclusionsThere is a bi-directional association between epilepsy and dementia. with either condition carrying a nearly 2-fold risk of developing the other when compared to controls.

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Illiteracy, dementia risk, and cognitive trajectories among older adults with low education

Neurology ◽

10.1212/wnl.0000000000008587 ◽

2019 ◽

Vol 93 (24) ◽

pp. e2247-e2256 ◽

Cited By ~ 3

Author(s):

Miguel Arce Rentería ◽

Jet M.J. Vonk ◽

Gloria Felix ◽

Justina F. Avila ◽

Laura B. Zahodne ◽

...

Keyword(s):

Older Adults ◽

Cognitive Decline ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Independent Effect ◽

Growth Curve Models ◽

Cox Proportional Hazards Models ◽

Dementia Risk ◽

Incident Dementia ◽

Low Education

ObjectiveTo investigate whether illiteracy was associated with greater risk of prevalent and incident dementia and more rapid cognitive decline among older adults with low education.MethodsAnalyses included 983 adults (≥65 years old, ≤4 years of schooling) who participated in a longitudinal community aging study. Literacy was self-reported (“Did you ever learn to read or write?”). Neuropsychological measures of memory, language, and visuospatial abilities were administered at baseline and at follow-ups (median [range] 3.49 years [0–23]). At each visit, functional, cognitive, and medical data were reviewed and a dementia diagnosis was made using standard criteria. Logistic regression and Cox proportional hazards models evaluated the association of literacy with prevalent and incident dementia, respectively, while latent growth curve models evaluated the effect of literacy on cognitive trajectories, adjusting for relevant demographic and medical covariates.ResultsIlliterate participants were almost 3 times as likely to have dementia at baseline compared to literate participants. Among those who did not have dementia at baseline, illiterate participants were twice as likely to develop dementia. While illiterate participants showed worse memory, language, and visuospatial functioning at baseline than literate participants, literacy was not associated with rate of cognitive decline.ConclusionWe found that illiteracy was independently associated with higher risk of prevalent and incident dementia, but not with a more rapid rate of cognitive decline. The independent effect of illiteracy on dementia risk may be through a lower range of cognitive function, which is closer to diagnostic thresholds for dementia than the range of literate participants.

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Long-Term Exposure to Ambient Hydrocarbons Increases Dementia Risk in People Aged 50 Years and above in Taiwan

Current Alzheimer Research ◽

10.2174/1567205017666200103112443 ◽

2020 ◽

Vol 16 (14) ◽

pp. 1276-1289

Author(s):

Han-Wei Zhang ◽

Victor C. Kok ◽

Shu-Chun Chuang ◽

Chun-Hung Tseng ◽

Chin-Teng Lin ◽

...

Keyword(s):

Air Pollutants ◽

Proportional Hazards ◽

The Elderly ◽

Cox Proportional Hazards ◽

Proportional Hazards Regression ◽

Hazard Ratios ◽

Dementia Risk ◽

Disease Exposure ◽

Total Hydrocarbons

Background: Alzheimer’s disease, the most common cause of dementia among the elderly, is a progressive and irreversible neurodegenerative disease. Exposure to air pollutants is known to have adverse effects on human health, however, little is known about hydrocarbons in the air that can trigger a dementia event. Objective: We aimed to investigate whether long-term exposure to airborne hydrocarbons increases the risk of developing dementia. Method: The present cohort study included 178,085 people aged 50 years and older in Taiwan. Cox proportional hazards regression analysis was used to fit the multiple pollutant models for two targeted pollutants, including total hydrocarbons and non-methane hydrocarbons, and estimated the risk of dementia. Results: Before controlling for multiple pollutants, hazard ratios with 95% confidence intervals for the overall population were 7.63 (7.28-7.99, p <0.001) at a 0.51-ppm increases in total hydrocarbons, and 2.94 (2.82-3.05, p <0.001) at a 0.32-ppm increases in non-methane hydrocarbons. The highest adjusted hazard ratios for different multiple-pollutant models of each targeted pollutant were statistically significant (p <0.001) for all patients: 11.52 (10.86-12.24) for total hydrocarbons and 9.73 (9.18-10.32) for non-methane hydrocarbons. Conclusion: Our findings suggest that total hydrocarbons and non-methane hydrocarbons may be contributing to dementia development.

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Abstract WP479: Associations Between Vascular Risk, Amyloid Burden and Incident Dementia: The ARIC-PET Study

Stroke ◽

10.1161/str.51.suppl_1.wp479 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Rebecca F Gottesman ◽

Aozhou Wu ◽

Josef Coresh ◽

Clifford R Jack ◽

David S Knopman ◽

...

Keyword(s):

Risk Factors ◽

Proportional Hazards ◽

Brain Mri ◽

Amyloid Β ◽

Standardized Uptake Value ◽

Cox Proportional Hazards ◽

Vascular Risk ◽

Brain Volumes ◽

Dementia Risk ◽

Incident Dementia

Background: Midlife vascular risk factors (MVRF) are associated with incident dementia. Similarly, amyloid β(Aβ) and neurodegeneration (e.g.brain volumes), as parts of the Alzheimer’s Disease (AD) ATN framework, are associated with cognition. Whether vascular and AD-associated factors contribute to dementia independently or interact synergistically to reduce cognitive ability is not well understood. Methods: Recruited from 3 U.S. communities, ARIC-PET participants were followed from 1987-89 (45-64 yo) through 2016-17 (74-94 yo). Cognition was evaluated in 2011-13 (ages 69-88), and twice more, every 2-3 years. In 2011-13, nondemented ARIC-PET participants had a brain MRI, with measurement of white matter hyperintensities (WMH) and brain volumes, with florbetapir (Aβ) PET scans in 2012-14; global cortical standardized uptake value ratio (SUVR) was log-transformed and standardized. Dementia was classified by expert review, as well as phone and medical record surveillance. The relative contributions of vascular risk (MVRF, WMH volume) and AD pathology (elevated Aβ SUVR, smaller AD signature region volumes) to incident dementia were evaluated with Cox proportional hazards regression. Results: In 298 individuals, 36 developed dementia. In models with key MVRF, demographics, and Aβ SUVR, hypertension and Aβ each independently predicted dementia risk (per SD of Aβ SUVR: HR 2.57, 95% CI 1.72-3.84; hypertension: HR 2.57, 95% CI 1.16-5.67), but didn’t interact on dementia risk. WMH (per SD: HR 1.51, 95% CI 1.03-2.20) and Aβ SUVR (per SD: HR 2.52, 95% CI 1.83-3.47) each contributed to incident dementia but WMH lost significance when MVRF were added to the model. Smaller AD signature regions were associated with incident dementia, independent of Aβ SUVR, and remained significant after adjustment for MVRF (HR per SD 2.18, 95% CI 1.18-4.01). Conclusions: Midlife hypertension and late-life Aβ independently contribute to dementia risk, but don’t synergize on a multiplicative scale. Neurodegeneration (e.g.smaller AD signature region volume) is also associated with incident dementia, independent of Aβ and MVRF. Multiple pathways leading to dementia should be considered when evaluating risk factors and interventions to reduce the burden of dementia.

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Blood pressure from mid‐ to late life and risk of incident dementia

Neurology ◽

10.1212/wnl.0000000000004741 ◽

2017 ◽

Vol 89 (24) ◽

pp. 2447-2454 ◽

Cited By ~ 46

Author(s):

Emer R. McGrath ◽

Alexa S. Beiser ◽

Charles DeCarli ◽

Kendra L. Plourde ◽

Ramachandran S. Vasan ◽

...

Keyword(s):

Blood Pressure ◽

Systolic Hypertension ◽

Proportional Hazards ◽

Late Life ◽

Cox Proportional Hazards ◽

Elevated Blood Pressure ◽

Elevated Blood ◽

Dementia Risk ◽

Incident Dementia ◽

Steep Decline

Objective:To determine the association between blood pressure during midlife (40–64 years) to late life (≥65 years) and risk of incident dementia.Methods:This study included 1,440 (758 women, mean age 69 ± 6 years) Framingham Offspring participants who were free of dementia and attended 5 consecutive examinations at 4-year intervals starting at midlife (1983–1987, mean age 55 years) until late life (1998–2001, mean 69 years) and subsequently were followed up for incident dementia (mean 8 years). We determined the effect of midlife hypertension (≥140/90 mm Hg), late life hypertension, lower late life blood pressure (<100/70 mm Hg), persistence of hypertension during mid- to late life, and steep decline in blood pressure from mid- to late life over an 18-year exposure period.Results:During the follow-up period, 107 participants (71 women) developed dementia. Using multivariable Cox proportional hazards models, we found that midlife systolic hypertension (hazard ratio [HR] 1.57, 95% confidence interval [CI] 1.05–2.35) and persistence of systolic hypertension into late life (HR 1.96, 95% CI 1.25–3.09) were associated with an elevated risk of incident dementia. However, in individuals with low to normal blood pressure (≤140/90 mm Hg) at midlife, a steep decline in systolic blood pressure during mid- to late life was also associated with a >2-fold increase in dementia risk (HR 2.40, 95% CI 1.39–4.15).Conclusions:Elevated blood pressure during midlife, persistence of elevated blood pressure into late life, and, among nonhypertensives, a steep decline in blood pressure during mid- to late life were associated with an increased dementia risk in a community-based cohort. Our data highlight the potential sustained cognitive benefits of lower blood pressures in midlife but also suggest that declining blood pressure in older adults with prehypertension or normotension, but not in those with hypertension, may be a risk marker for dementia.

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Neuropsychological Criteria for Mild Cognitive Impairment and Dementia Risk in the Framingham Heart Study

Journal of the International Neuropsychological Society ◽

10.1017/s1355617716000199 ◽

2016 ◽

Vol 22 (9) ◽

pp. 937-943 ◽

Cited By ~ 41

Author(s):

Amy J. Jak ◽

Sarah R. Preis ◽

Alexa S. Beiser ◽

Sudha Seshadri ◽

Philip A. Wolf ◽

...

Keyword(s):

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Diagnostic Criteria ◽

Framingham Heart Study ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Alternative Methods ◽

Cognitive Test ◽

Incident Dementia ◽

Heart Study

AbstractObjectives: To refine mild cognitive impairment (MCI) diagnostic criteria, we examined progression to dementia using two approaches to identifying MCI. Methods: A total of 1203 Framingham Heart Study participants were classified at baseline as cognitively normal or MCI (overall and four MCI subtypes) via conventional Petersen/Winblad criteria (single cognitive test impaired per domain, >1.5 SD below expectations) or Jak/Bondi criteria (two tests impaired per domain, >1 SD below norms). Cox proportional hazards models were constructed to examine the association between each MCI definition and incident dementia. Results: The Petersen/Winblad criteria classified 34% of participants as having MCI while the Jak/Bondi criteria classified 24% as MCI. Over a mean follow-up of 9.7 years, 58 participants (5%) developed incident dementia. Both MCI criteria were associated with incident dementia [Petersen/Winblad: hazards ratio (HR) = 2.64; p-value=.0002; Jak/Bondi: HR=3.30; p-value <.0001]. When both MCI definitions were included in the same model, only the Jak/Bondi definition remained statistically significantly associated with incident dementia (HR=2.47; p-value=.008). Multi-domain amnestic and single domain non-amnestic MCI subtypes were significantly associated with incident dementia for both diagnostic approaches (all p-values <.01). Conclusions: The Jak/Bondi MCI criteria had a similar association with dementia as the conventional Petersen/Winblad MCI criteria, despite classifying ~30% fewer participants as having MCI. Further exploration of alternative methods to conventional MCI diagnostic criteria is warranted. (JINS, 2016, 22, 937–943)

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Influence of Diabetes Duration and Glycemic Control on Dementia: A Cohort Study

The Journals of Gerontology Series A ◽

10.1093/gerona/glab221 ◽

2021 ◽

Author(s):

Fu-Rong Li ◽

Hai-Lian Yang ◽

Rui Zhou ◽

Jia-Zhen Zheng ◽

Guo-Chong Chen ◽

...

Keyword(s):

Glycemic Control ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Diabetes Duration ◽

Self Report ◽

Diabetes Diagnosis ◽

Duration Of Diabetes ◽

Incident Dementia ◽

Patients With Diabetes ◽

The Uk

Abstract Background To investigate the influence of diabetes duration and glycemic control, assessed by glycated hemoglobin (HbA1c) levels, on risk of incident dementia. Methods The present study is a prospective study of 461,563 participants from the UK Biobank. The age at diabetes diagnosis was determined by self-report. Diabetes duration was calculated as baseline age minus age at diagnosis. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) with 95% confidential intervals (CIs). Results During a median follow-up of 8.1 y, 2,233 dementia cases were recorded. As compared with normoglycemic individuals, individuals with diabetes had higher risk of all-cause dementia, and the risk increased with increasing duration of diabetes; compared with participants with diabetes duration of <5 y, the multivariable-adjusted HRs (95% CIs) were 1.49 (1.12-1.97), 1.71 (1.21-2.41), and 2.15 (1.60-2.90) for those with diabetes durations ≥5 to < 10, ≥10 to <15, and ≥ 15 y, respectively (P for trend < 0.001). Among participants with diabetes, those with both longer diabetes duration (diabetes duration ≥10 y) and poor glycemic control (HbA1c ≥8%) had the highest risk of All-cause dementia (multivariable-adjusted HR =2.07, 95% CI 1.45, 2.94), compared with patients with shorter duration of diabetes and better glycemic control (diabetes duration <10 y and HbA1c <8%). Conclusions Diabetes duration appeared to be associated with the risk of incident dementia due to factors beyond glycemic control. Clinicians should consider not only glycemic control but also diabetes duration in dementia risk assessments for patients with diabetes.

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Intentional Weight Loss and Obesity-Related Cancer Risk

JNCI Cancer Spectrum ◽

10.1093/jncics/pkz054 ◽

2019 ◽

Vol 3 (4) ◽

Cited By ~ 9

Author(s):

Juhua Luo ◽

Michael Hendryx ◽

JoAnn E Manson ◽

Jane C Figueiredo ◽

Erin S LeBlanc ◽

...

Keyword(s):

Weight Loss ◽

Cancer Risk ◽

Postmenopausal Women ◽

Proportional Hazards ◽

Epidemiologic Studies ◽

Cox Proportional Hazards ◽

Self Report ◽

Intentional Weight Loss ◽

Colon And Rectum ◽

Kidney Liver

Abstract Background Epidemiologic studies regarding weight loss and subsequent cancer risk are sparse. The study aim was to evaluate the association between weight change by intentionality and obesity-related cancer incidence in the Women’s Health Initiative Observational Study. Eleven cancers were considered obesity related: breast, ovary, endometrium, colon and rectum, esophagus, kidney, liver, multiple myeloma, pancreas, stomach, and thyroid. Methods Postmenopausal women (n = 58 667) aged 50–79 years had body weight and waist circumference (WC) measured at baseline and year 3. Weight or WC change was categorized as stable (change < ±5%), loss (≥5%), and gain (≥5%). Self-report at year 3 characterized weight loss as intentional or unintentional. During the subsequent 12 years (mean) of follow-up, 6033 incident obesity-related cancers were identified. Relationships were evaluated using multivariable Cox proportional hazards regression models. Results Compared to women with stable weight, women with intentional weight loss had lower obesity-related cancer risk (hazard ratio [HR] = 0.88, 95% confidence interval [CI] = 0.80 to 0.98). A similar result was observed for intentional WC reduction (HR = 0.88, 95% CI = 0.80 to 0.96). Among all cancers, intentional weight loss was most strongly associated with endometrial cancer (HR = 0.61, 95% CI = 0.42 to 0.88). Intentional WC loss was also associated with lower colorectal cancer risk (HR = 0.79, 95% CI = 0.63 to 0.99). Unintentional weight loss or weight gain was not associated with overall obesity-related cancer risk. Conclusion Intentional weight or WC loss in postmenopausal women was associated with lower risk of obesity-related cancer. These findings suggest that postmenopausal women who intentionally lose weight can reduce their obesity-related cancer risk.

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Association Between Informant-Reported Sleep Disturbance and Incident Dementia: An Analysis of the National Alzheimer’s Coordinating Center Uniform Data Set

Journal of Applied Gerontology ◽

10.1177/0733464820967202 ◽

2020 ◽

pp. 073346482096720

Author(s):

Woojung Lee ◽

Shelly L. Gray ◽

Douglas Barthold ◽

Donovan T. Maust ◽

Zachary A. Marcum

Keyword(s):

Older Adults ◽

Sleep Disturbance ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Cognitive Screening ◽

Cognitive Level ◽

Data Set ◽

Cox Proportional Hazards Models ◽

Incident Dementia ◽

Normal Cognition

Informants’ reports can be useful in screening patients for future risk of dementia. We aimed to determine whether informant-reported sleep disturbance is associated with incident dementia, whether this association varies by baseline cognitive level and whether the severity of informant-reported sleep disturbance is associated with incident dementia among those with sleep disturbance. A longitudinal retrospective cohort study was conducted using the uniform data set collected by the National Alzheimer’s Coordinating Center. Older adults without dementia at baseline living with informants were included in analysis. Cox proportional hazards models showed that participants with an informant-reported sleep disturbance were more likely to develop dementia, although this association may be specific for older adults with normal cognition. In addition, older adults with more severe sleep disturbance had a higher risk of incident dementia than those with mild sleep disturbance. Informant-reported information on sleep quality may be useful for prompting cognitive screening.

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