Illiteracy, dementia risk, and cognitive trajectories among older adults with 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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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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Neighborhood greenspace exposure as a protective factor in dementia risk among U.S. adults 75 years or older: a cohort study

Environmental Health ◽

10.1186/s12940-022-00830-6 ◽

2022 ◽

Vol 21 (1) ◽

Author(s):

Erik D. Slawsky ◽

Anjum Hajat ◽

Isaac C. Rhew ◽

Helen Russette ◽

Erin O. Semmens ◽

...

Keyword(s):

Older Adults ◽

Protective Factor ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Future Research ◽

Cox Proportional Hazards Models ◽

Linear Distance ◽

Dementia Risk ◽

Normalized Difference Vegetative Index ◽

Multiple Covariates

Abstract Background Research suggests that greenspace may confer neurocognitive benefits. This study examines whether residential greenspace is associated with risk of dementia among older adults. Methods Greenspace exposure was computed for 3047 participants aged 75 years and older enrolled in the Gingko Evaluation of Memory Study (GEMS) across four U.S. sites that prospectively evaluated dementia and its subtypes, Alzheimer’s disease (AD), vascular dementia (VaD), and mixed pathologies, using neuropsychiatric evaluations between 2000 and 2008. After geocoding participant residences at baseline, three greenspace metrics—Normalized Difference Vegetative Index, percent park overlap within a 2-km radius, and linear distance to nearest park—were combined to create a composite residential greenspace measure categorized into tertiles. Cox proportional hazards models estimated the associations between baseline greenspace and risk of incident all-cause dementia, AD, and Mixed/VaD. Results Compared to low residential greenspace, high residential greenspace was associated with a reduced risk of dementia (HR = 0.76 95% CI: 0.59,0.98) in models adjusted for multiple covariates. After additional adjustment for behavioral characteristics, Apolipoprotein E ɛ4 status, and other covariates, the association was slightly attenuated (HR = 0.82; 95% CI:0.63,1.06). Those exposed to medium levels of greenspace also had 28% lower risk (HR = 0.72; CI: 0.55, 0.95) of dementia compared to those with low greenspace in adjusted models. Subtype associations between high residential greenspace and AD were not statistically significant. Greenspace was not found to be significantly associated with mixed/vascular pathologies. Conclusions This study showed evidence for an association between residential greenspace and all-cause dementia among older adults. Future research with larger sample size, precise characterization of different dementia subtypes, and assessment of residential greenspace earlier in life may help clarify the role between exposure to greenspace and dementia risk.

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Suicide risk within one year of cognitive impairment diagnosis in older adults: a nationwide retrospective cohort study

10.21203/rs.2.19129/v1 ◽

2019 ◽

Author(s):

Jae Woo Choi ◽

Kang Soo Lee ◽

Euna Han

Keyword(s):

Alzheimer’S Disease ◽

Older Adults ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mental Disorders ◽

Suicide Risk ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Models ◽

One Year

Abstract Background This study aims to investigate suicide risk within one year of receiving a diagnosis of cognitive impairment in older adults without mental disorders. Methods This study used National Health Insurance Service-Senior Cohort data on older adults with newly diagnosed cognitive impairment including Alzheimer’s disease, vascular dementia, other/unspecified dementia, and mild cognitive impairment from 2004 to 2012. We selected 41,195 older adults without cognitive impairment through 1:1 propensity score matching using age, gender, Charlson Comorbidity Index, and index year, with follow-up throughout 2013. We eliminated subjects with mental disorders and estimated adjusted hazard ratios (AHR) of suicide deaths within one year after diagnosis using the Cox proportional hazards models. Results We identified 49 suicide deaths during the first year after cognitive impairment diagnosis. The proportion of observed suicide deaths was the highest within one year after cognitive impairment diagnosis (48.5% of total); older adults with cognitive impairment were at a higher suicide risk than those without cognitive impairment (AHR, 1.89; 95% confidence interval [CI], 1.18–3.04). Subjects with Alzheimer’s disease and other/unspecified dementia were at greater suicide risk than those without cognitive impairment (AHR, 1.94, 1.94; 95% CI, 1.12–3.38, 1.05–3.58). Suicide risk in female and young-old adults (60–74 years) with cognitive impairment was higher than in the comparison group (AHR, 2.61, 5.13; 95% CI, 1.29–5.28, 1.48–17.82). Conclusions Older patients with cognitive impairment were at increased suicide risk within one year of diagnosis. Early intervention for suicide prevention should be provided to older adults with cognitive impairment.

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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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Metformin vs sulfonylurea use and risk of dementia in US veterans aged ≥65 years with diabetes

Neurology ◽

10.1212/wnl.0000000000004586 ◽

2017 ◽

Vol 89 (18) ◽

pp. 1877-1885 ◽

Cited By ~ 41

Author(s):

Ariela R. Orkaby ◽

Kelly Cho ◽

Jean Cormack ◽

David R. Gagnon ◽

Jane A. Driver

Keyword(s):

Lower Risk ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Hazard Ratio ◽

Confounding By Indication ◽

Cox Proportional Hazards Models ◽

Incident Dementia ◽

Us Veterans

Objective:To determine whether metformin is associated with a lower incidence of dementia than sulfonylureas.Methods:This was a retrospective cohort study of US veterans ≥65 years of age with type 2 diabetes who were new users of metformin or a sulfonylurea and had no dementia. Follow-up began after 2 years of therapy. To account for confounding by indication, we developed a propensity score (PS) and used inverse probability of treatment weighting (IPTW) methods. Cox proportional hazards models estimated the hazard ratio (HR) of incident dementia.Results:We identified 17,200 new users of metformin and 11,440 new users of sulfonylureas. Mean age was 73.5 years and mean HbA1c was 6.8%. Over an average follow-up of 5 years, 4,906 cases of dementia were diagnosed. Due to effect modification by age, all analyses were conducted using a piecewise model for age. Crude hazard ratio [HR] for any dementia in metformin vs sulfonylurea users was 0.67 (95% confidence interval [CI] 0.61–0.73) and 0.78 (95% CI 0.72–0.83) for those <75 years of age and ≥75 years of age, respectively. After PS IPTW adjustment, results remained significant in veterans <75 years of age (HR 0.89; 95% CI 0.79–0.99), but not for those ≥75 years of age (HR 0.96; 95% CI 0.87–1.05). A lower risk of dementia was also seen in the subset of younger veterans who had HbA1C values ≥7% (HR 0.76; 95% CI 0.63–0.91), had good renal function (HR 0.86; 95% CI 0.76–0.97), and were white (HR 0.87; 95% CI 0.77–0.99).Conclusions:After accounting for confounding by indication, metformin was associated with a lower risk of subsequent dementia than sulfonylurea use in veterans <75 years of age. Further work is needed to identify which patients may benefit from metformin for the prevention of dementia.

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Association between anticholinergic burden and dementia in UK Biobank

Innovation in Aging ◽

10.1093/geroni/igab046.3356 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. 936-936

Author(s):

Jure Mur ◽

Simon Cox ◽

Riccardo Marioni ◽

Tom Russ ◽

Graciela Muniz-Terrera

Keyword(s):

Proportional Hazards ◽

Cox Proportional Hazards ◽

Anticholinergic Drugs ◽

Uk Biobank ◽

General Measure ◽

Future Studies ◽

Cox Proportional Hazards Models ◽

Dementia Risk ◽

Anticholinergic Burden

Abstract Previous studies on the association between the long-term use of anticholinergic drugs and dementia report heterogenous results. This variability could be due to, among other factors, different anticholinergic scales used, and differential effects of distinct classes of anticholinergic drugs. Here, we use 171,775 participants of UK Biobank with linked GP prescription records to calculate the cumulative annual anticholinergic burden (ACB) and ascertain dementia diagnoses through GP- and inpatient records. We then use Cox proportional hazards models to compare 13 anticholinergic scales and anticholinergic burden (ACB) due to different classes of drugs in their association with dementia. We find dementia to be more strongly predicted by ACB than by polypharmacy across most anticholinergic scales (standardised ORs range: 1.027-1.125). Furthermore, not only the baseline ACB, but the slope of the longitudinal trajectory of ACB (HR=1.094; 95% CI: 1.068-1.119) is predictive of dementia. However, the association between ACB and dementia holds only for some classes of drugs – especially antidepressants, antiepileptics, and high-ceiling antidiuretics. Moreover, we do not find a clear relationship between reported anticholinergic potency and dementia risk. The heterogeneity in findings on the association between ACB and dementia may in part be due to different effects for different classes of drugs. Future studies should establish such differences in more detail and further examine the practicality of using a general measure of anticholinergic potency as it relates to the risk of dementia.

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Restriction of Pharmacoepidemiologic Cohorts to Initiators of Medications in Unrelated Preventive Drug Classes to Reduce Confounding by Frailty in Older Adults

American Journal of Epidemiology ◽

10.1093/aje/kwz083 ◽

2019 ◽

Vol 188 (7) ◽

pp. 1371-1382 ◽

Cited By ~ 2

Author(s):

Henry T Zhang ◽

Leah J McGrath ◽

Alan R Ellis ◽

Richard Wyss ◽

Jennifer L Lund ◽

...

Keyword(s):

Older Adults ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Standardized Mortality Ratio ◽

Drug Classes ◽

Cox Proportional Hazards Models ◽

Hazard Ratios ◽

All Cause Mortality ◽

Preventive Drug ◽

Mortality Ratio

Abstract Nonexperimental studies of the effectiveness of seasonal influenza vaccine in older adults have found 40%–60% reductions in all-cause mortality associated with vaccination, potentially due to confounding by frailty. We restricted our cohort to initiators of medications in preventive drug classes (statins, antiglaucoma drugs, and β blockers) as an approach to reducing confounding by frailty by excluding frail older adults who would not initiate use of these drugs. Using a random 20% sample of US Medicare beneficiaries, we framed our study as a series of nonrandomized “trials” comparing vaccinated beneficiaries with unvaccinated beneficiaries who had an outpatient health-care visit during the 5 influenza seasons occurring in 2010–2015. We pooled data across trials and used standardized-mortality-ratio–weighted Cox proportional hazards models to estimate the association between influenza vaccination and all-cause mortality before influenza season, expecting a null association. Weighted hazard ratios among preventive drug initiators were generally closer to the null than those in the nonrestricted cohort. Restriction of the study population to statin initiators with an uncensored approach resulted in a weighted hazard ratio of 1.00 (95% confidence interval: 0.84, 1.19), and several other hazard ratios were above 0.95. Restricting the cohort to initiators of medications in preventive drug classes can reduce confounding by frailty in this setting, but further work is required to determine the most appropriate criteria to use.

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Periodontal disease and incident dementia

Neurology ◽

10.1212/wnl.0000000000010312 ◽

2020 ◽

Vol 95 (12) ◽

pp. e1660-e1671

Author(s):

Ryan T. Demmer ◽

Faye L. Norby ◽

Kamakshi Lakshminarayan ◽

Keenan A. Walker ◽

James S. Pankow ◽

...

Keyword(s):

Periodontal Disease ◽

Proportional Hazards ◽

Brain Mri ◽

Cox Proportional Hazards ◽

Incidence Density ◽

Adjusted Risk ◽

Cox Proportional Hazards Models ◽

Incident Dementia ◽

Increased Risk ◽

Combined Dementia

ObjectiveTo test the hypothesis that periodontal disease would be associated with increased risk for dementia and mild cognitive impairment (MCI) by assessing dementia/MCI outcomes after a baseline periodontal examination.MethodsParticipants enrolled in the Atherosclerosis Risk in Communities study with a clinical periodontal examination (or edentulous participants) at visit 4 (1996–1998; mean ± SD age 63 ± 6 years, 55% female, 21% black) and adjudicated dementia outcomes through 2016 were included (n = 8,275). A subgroup of 4,559 participants had adjudicated dementia and MCI assessments at visit 5 (2011–2013). Participants received a full-mouth periodontal examination and were classified into periodontal profile classes (PPCs) based on the severity and extent of gingival inflammation and attachment loss. MCI and dementia were determined via neurocognitive testing, neurological examination and history, informant interviews, and brain MRI in a subset. Cox proportional hazards models regressed incident dementia on PPCs. Relative risk regression models were used for the composite of MCI/dementia.ResultsThe cumulative incidence and incidence density of dementia during follow-up (average 18.4 years) were 19% (n = 1,569) and 11.8 cases per 1,000 person-years. Multivariable adjusted hazard ratios for incident dementia among participants with severe PPC or edentulism (vs periodontal healthy) were 1.22 (95% confidence interval [CI] 1.01–1.47) and 1.21 (95% CI 0.99–1.48), respectively. For the combined dementia/MCI outcome, adjusted risk ratios among participants with mild/intermediate PPC, severe PPC, or edentulism (vs periodontal healthy) were 1.22 (95% CI 1.00–1.48), 1.15 (95% CI 0.88–1.51), and 1.90 (95% CI 1.40–2.58). Results were stronger among younger (≤62 years) participants (p for interaction = 0.02).ConclusionPeriodontal disease was modestly associated with incident MCI and dementia in a community-based cohort of black and white participants.

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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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Indicators of Crash Risk in Older Adults: A Longitudinal Analysis From the ACTIVE Study

Journal of Aging and Health ◽

10.1177/08982643211031346 ◽

2021 ◽

pp. 089826432110313

Author(s):

Karlene K. Ball ◽

Olivio J. Clay ◽

Jerri D. Edwards ◽

Bernadette A. Fausto ◽

Katie M. Wheeler ◽

...

Keyword(s):

Older Adults ◽

Proportional Hazards ◽

Secondary Data ◽

Cox Proportional Hazards ◽

Crash Risk ◽

Significant Finding ◽

Site Location ◽

Cox Proportional Hazards Models ◽

Male Sex

Objective: This study aims to examine indicators of crash risk longitudinally in older adults ( n = 486). Method: This study applied secondary data analyses of the 10 years of follow-up for the ACTIVE study combined with state-recorded crash records from five of the six participating sites. Cox proportional hazards models were first used to examine the effect of each variable of interest at baseline after controlling for miles driven and then to assess the three cognitive composites as predictors of time to at-fault crash in covariate-adjusted models. Results: Older age, male sex, and site location were each predictive of higher crash risk. Additionally, worse scores on the speed of processing cognitive composite were associated with higher crash risk. Discussion: Results support previous findings that both age and male sex are associated with higher crash risk. Our significant finding of site location could be attributed to the population density of our testing sites and transportation availability.

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