Examining the Combined Estimated Effects of Hearing Impairment and Depression on Cognitive Decline and Dementia

Abstract Late-life depression is a comorbidity which may co-occur in older adults with hearing loss- each as prevalent and independent modifiable risk factors for dementia. We used data from 1,820 participants (74 ± 2.8 years, 38% Black race) from the Health Aging and Body Composition Study to test if the hearing loss-dementia/cognitive decline (Modified Mini Mental State Exam[3MS] and Digit Symbol Substitution[DSST]) relationship differed in hearing impaired participants who also had depressive symptoms. Depressive symptoms were defined as CES-D 10 ≥10) at one or more visits from years 1-5. Algorithmic incident dementia defined using medication use, hospitalizations and cognitive test scores. Audiometric hearing loss was measured at year 5 and categorized as normal/mild vs ≥moderate loss. In linear mixed models adjusted for demographic and clinical covariates, presence of both hearing loss and depressive symptoms (vs. having neither) was associated with faster rates of decline in 3MS (-0.30, 95% CI:-0.78, -0.19) and DSST (-0.35,95% CI:-0.67, -0.03) over 10 years of follow-up. Both hearing loss and depressive symptoms (vs. neither) was associated with increased risk (hazard ratio (HR):2.91, 95%CI: 1.59, 5.33) of incident dementia in multivariable-adjusted Cox proportional hazards models. Comorbid conditions among hearing impaired older adults should be considered and may aid in dementia prevention and management strategies.

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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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Associations of Hearing Loss and Depressive Symptoms With Incident Disability in Older Adults: Health, Aging, and Body Composition Study

The Journals of Gerontology Series A ◽

10.1093/gerona/gly251 ◽

2018 ◽

Vol 75 (3) ◽

pp. 531-536 ◽

Cited By ~ 7

Author(s):

Nicole M Armstrong ◽

Jennifer A Deal ◽

Joshua Betz ◽

Stephen Kritchevsky ◽

Sheila Pratt ◽

...

Keyword(s):

Older Adults ◽

Hearing Loss ◽

Body Composition ◽

Depressive Symptoms ◽

Mobility Disability ◽

Body Composition Study ◽

Increased Risk ◽

Health Aging ◽

Composition Study ◽

Adl Disability

Abstract Background Depressive symptoms and hearing loss (HL) are independently associated with increased risk of incident disability; whether the increased risk is additive is unclear. Methods Cox Proportional Hazards models were used to assess joint associations of HL (normal, mild, moderate/severe) and late-life depressive symptoms (defined by a score of ≥8 on the 10-item Center for Epidemiologic Studies-Depression scale) with onset of mobility disability (a lot of difficulty or inability to walk ¼ mile and/or climb 10 steps) and any disability in activities of daily living (ADL), among 2,196 participants of the Health, Aging and Body Composition Study, a cohort of well-functioning older adults aged 70–79 years. Models were adjusted for age, race, sex, education, diabetes, hypertension, and body mass index. Results Relative to participants with normal hearing and without depressive symptoms, participants without depressive symptoms who had mild or moderate/severe HL had increased risk of incident mobility and ADL disability (hazard ratio [HR] for mobility disability, mild HL:1.34, 95% confidence interval [CI]: 1.09, 1.64 and HR for mobility disability, moderate/severe HL: 1.37, 95% CI: 1.08, 1.75 and HR for ADL disability, mild HL: 1.32, 95% CI: 1.08, 1.63, and HR for ADL disability, moderate/severe HL: 1.42, 95% CI: 1.11, 1.82). Among participants with depressive symptoms, mild HL (HR: 1.71, 95% CI: 1.09, 2.70) was associated with increased risk of incident mobility disability. Conclusions Independent of depressive symptoms, risk of incident disability was greater in older adults with HL, regardless of severity. Further research into HL interventions may delay disability onset.

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Long‐Term Blood Pressure Variability and Risk of Cognitive Decline and Dementia Among Older Adults

Journal of the American Heart Association ◽

10.1161/jaha.120.019613 ◽

2021 ◽

Author(s):

Michael E. Ernst ◽

Joanne Ryan ◽

Enayet K. Chowdhury ◽

Karen L. Margolis ◽

Lawrence J. Beilin ◽

...

Keyword(s):

Blood Pressure ◽

Older Adults ◽

Cognitive Impairment ◽

Cognitive Decline ◽

Blood Pressure Variability ◽

Link Type ◽

Incident Dementia ◽

Increased Risk ◽

The Impact

Background Blood pressure variability (BPV) in midlife increases risk of late‐life dementia, but the impact of BPV on the cognition of adults who have already reached older ages free of major cognitive deficits is unknown. We examined the risk of incident dementia and cognitive decline associated with long‐term, visit‐to‐visit BPV in a post hoc analysis of the ASPREE (Aspirin in Reducing Events in the Elderly) trial. Methods and Results ASPREE participants (N=19 114) were free of dementia and significant cognitive impairment at enrollment. Measurement of BP and administration of a standardized cognitive battery evaluating global cognition, delayed episodic memory, verbal fluency, and processing speed and attention occurred at baseline and follow‐up visits. Time‐to‐event analysis using Cox proportional hazards regression models were used to calculate hazard ratios (HR) and corresponding 95% CI for incident dementia and cognitive decline, according to tertile of SD of systolic BPV. Individuals in the highest BPV tertile compared with the lowest had an increased risk of incident dementia and cognitive decline, independent of average BP and use of antihypertensive drugs. There was evidence that sex modified the association with incident dementia (interaction P =0.02), with increased risk in men (HR, 1.68; 95% CI, 1.19–2.39) but not women (HR, 1.01; 95% CI, 0.72–1.42). For cognitive decline, similar increased risks were observed for men and women (interaction P =0.15; men: HR, 1.36; 95% CI, 1.16–1.59; women: HR, 1.14; 95% CI, 0.98–1.32). Conclusions High BPV in older adults without major cognitive impairment, particularly men, is associated with increased risks of dementia and cognitive decline. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01038583; isrctn.com . Identifier: ISRCTN83772183.

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Subjective cognitive decline and subsequent dementia: a nationwide cohort study of 579,710 people (66 year-olds) in South Korea

10.21203/rs.2.19062/v1 ◽

2019 ◽

Author(s):

Yeong Chan Lee ◽

Jae Myeong Kang ◽

Hyewon Lee ◽

Kiwon Kim ◽

Soyeon Kim ◽

...

Keyword(s):

Depressive Symptoms ◽

South Korea ◽

Cognitive Decline ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Population Based ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Subjective Cognitive Decline ◽

Increased Risk

Abstract Background: Subjective cognitive decline (SCD) is a potential risk factor for dementia. We aimed to investigate the association between SCD and subsequent dementia in a nationwide population-based cohort in South Korea.Methods: This cohort included 579,710 66-year-old adults who completed a questionnaire about SCD and were followed-up for a total of 3,870,293 person-years (average 6.68 years per person). Hazard ratios were estimated using the Cox proportional hazards model and compared between subjects with and without SCD.Results: Compared to subjects without SCD, those with SCD were more likely to develop dementia (incidence per 100,000 person-years: no SCD: 566.14; SCD: 859.35). After adjusting for potential confounding factors, the risk of subsequent dementia significantly increased in subjects with SCD, with an adjusted hazard ratio (aHR) of 1.38 (95% confidence interval [CI] 1.34 to 1.41). The risk of subsequent dementia was greatly increased in subjects with higher SCD scores (aHR=2.77, 95% CI 2.47 to 3.11). A significant association between SCD and dementia was observed in both depressive and non-depressive symptom groups (aHR=1.50, 95% CI 1.42 to 1.57 in subjects with depressive symptoms; aHR=1.33, 95% CI 1.29 to 1.37 in subjects without depressive symptoms; P =0.001).Conclusions: In the participating 66-year-old population, SCD was significantly associated with an increased risk of subsequent dementia, independent of the presence of depressive symptoms. Our findings suggest that SCD indicates a risk for dementia. Further studies are needed to delineate potential approaches to preventing the development of dementia in individuals with SCD.

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Gait Speed and Grip Strength Are Predictors of Cognitive Decline and Dementia in Older Individuals

Innovation in Aging ◽

10.1093/geroni/igab046.2454 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. 652-653

Author(s):

Suzanne Orchard ◽

Joanne Ryan ◽

Robyn Woods ◽

Galina Polekhina ◽

Elsdon Storey ◽

...

Keyword(s):

Older Adults ◽

Cognitive Decline ◽

Grip Strength ◽

Gait Speed ◽

Specific Interaction ◽

Cognitive Outcomes ◽

Older Individuals ◽

Incident Dementia ◽

Increased Risk ◽

Longitudinal Association

Abstract Lower gait speed and grip strength are common in older adults. However, the results of lower motor function on cognitive outcomes have been mixed. We examined the longitudinal association between baseline slow gait speed and weak grip strength, alone and in combination, with risk of incident dementia or cognitive decline in a cohort of older adults. Participants (n=19,114) aged 70 and over (65 if U.S. minority) without documented evidence of dementia, significant cognitive impairment, physical disability or previous cardiovascular disease at baseline, were recruited from community settings. Incident dementia was adjudicated by an expert panel using DSM-IV criteria. Incident cognitive decline was defined as a persistent intra-individual decline in score of >1.5 SD from baseline on any of the cognitive tests. Using cox proportional hazard models, slow gait speed at baseline was associated with an increased risk of dementia (63%) and cognitive decline (43%), over a median 4.7 years. Weak grip strength was not as strong a predictor, but was also associated with risk (43% and 11%, respectively). Both outcomes showed higher risk for dementia than cognitive decline. There was no gender-specific interaction. When considered together (adjusted for one another), gait speed and grip strength were both independently associated with cognitive decline and dementia. The synergistic association of these physical measures, each of which is readily administered in the clinic or home, serve as effective early markers of increasing risk of cognitive decline and incident dementia and thus, should be considered for routine health assessments for older adults.

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AGE-RELATED HEARING LOSS, LATE-LIFE DEPRESSION, AND RISK FOR INCIDENT DEMENTIA IN OLDER ADULTS

American Journal of Geriatric Psychiatry ◽

10.1016/j.jagp.2020.01.118 ◽

2020 ◽

Vol 28 (4) ◽

pp. S90-S93

Author(s):

Katharine Brewster ◽

Melanie Wall ◽

Alexandra Stein ◽

Sigal Zilcha-Mano ◽

Bret R. Rutherford

Keyword(s):

Older Adults ◽

Hearing Loss ◽

Late Life ◽

Late Life Depression ◽

Age Related ◽

Incident Dementia ◽

Age Related Hearing Loss

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Subjective cognitive decline and subsequent dementia: a nationwide cohort study of 579,710 people aged 66 years in South Korea

10.21203/rs.2.19062/v2 ◽

2020 ◽

Author(s):

Yeong Chan Lee ◽

Jae Myeong Kang ◽

Hyewon Lee ◽

Kiwon Kim ◽

Soyeon Kim ◽

...

Keyword(s):

Depressive Symptoms ◽

South Korea ◽

Cognitive Decline ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Depression Scale ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Subjective Cognitive Decline ◽

Increased Risk

Abstract Background Subjective cognitive decline (SCD) is a potential risk factor for dementia. We aimed to investigate the association between SCD and subsequent dementia in a nationwide population-based cohort in South Korea. Methods This cohort included 579,710 66-year-old adults who were followed for a total of 3,870,293 person-years (average 6.68±1.33 years per person). All subjects completed a questionnaire about subjective memory impairment, the Pre-screening Korean Dementia Screening Questionnaire (KDSQ-P), which included a validated 5-item derivative, and were determined to have SCD based on a single question assessing memory decline. Depressive symptoms were assessed in all subjects using a 3-item modified geriatric depression scale. Hazard ratios were estimated using the Cox proportional hazards model and compared between subjects with and without SCD. Results Compared to subjects without SCD, those with SCD were more likely to develop dementia (incidence per 1,000 person-years: non-SCD: 5.66; SCD: 8.59). After adjusting for potential confounding factors, the risk of subsequent dementia significantly increased in subjects with SCD, with an adjusted hazard ratio (aHR) of 1.38 (95% confidence interval [CI] 1.34 to 1.41). The risk of subsequent dementia was greatly increased in subjects with higher KDSQ-P scores (aHR = 2.77, 95% CI 2.47 to 3.11). A significant association between SCD and dementia was observed in both depressive and non-depressive symptom groups (aHR = 1.50, 95% CI 1.42 to 1.57 in subjects with depressive symptoms; aHR = 1.33, 95% CI 1.29 to 1.37 in subjects without depressive symptoms; P = 0.001). Conclusions In this population of 66-year-old individuals, SCD was significantly associated with an increased risk of subsequent dementia. This association was found in both depressive and non-depressive groups, with an increased risk of dementia in the presence of depressive symptoms. Our findings suggest that SCD indicates a risk for dementia. Further studies are needed to delineate potential approaches to preventing the development of dementia in individuals with SCD.

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APOE ε2ε4 genotype, incident AD and MCI, cognitive decline, and AD pathology in older adults

Neurology ◽

10.1212/wnl.0000000000005677 ◽

2018 ◽

Vol 90 (24) ◽

pp. e2127-e2134 ◽

Cited By ~ 13

Author(s):

Shahram Oveisgharan ◽

Aron S. Buchman ◽

Lei Yu ◽

Jose Farfel ◽

Vladimir Hachinski ◽

...

Keyword(s):

Older Adults ◽

Cognitive Impairment ◽

Cognitive Decline ◽

Reference Group ◽

Cox Proportional Hazards ◽

European Ancestry ◽

Linear Regression Models ◽

Mixed Effect ◽

Increased Risk ◽

Β Amyloid

ObjectiveTo examine the association of the APOE ε2ε4 genotype with incident Alzheimer disease (AD), mild cognitive impairment (MCI), cognitive decline, and AD pathology in older adults.MethodsWe used data from 2,151 older adults of European ancestry who were free of dementia at baseline and underwent structured annual clinical evaluation in a longitudinal study for incident AD and MCI, and cognitive decline. Postmortem examination in decedents documented pathologic AD and quantified β-amyloid and neurofibrillary tangles. Participants were stratified into 4 groups based on APOE genotyping: ε2ε4, ε4 (ε4ε4, ε4ε3), ε2 (ε2ε2, ε2ε3), with ε3ε3 carriers serving as the reference group. We used Cox proportional hazards models to examine the association of APOE genotype with incident AD and MCI. Linear mixed-effect models were used to examine the association with cognitive decline. Logistic and linear regression models were used to examine AD pathology. All the models controlled for age, sex, and education.ResultsOf the 2,151 participants included in this study, ε2ε4 accounted for 2.1%, ε3/4 and 4/4 21.8%, ε2/3 and 2/2 14.0%, and ε3ε3 62.1%. We did not observe a difference in the risk of AD for ε2ε4 compared to ε3ε3. In cases without cognitive impairment at baseline, ε2ε4 carriers had an increased risk of incident MCI (hazard ratio 2.13, 95% confidence interval 1.34–3.39, p = 0.002) and a faster rate of cognitive decline (estimate −0.047, SE 0.018, p = 0.008) compared to ε3ε3 carriers. In decedents (n = 1,100), ε2ε4 showed a 3-fold increased odds of pathologic AD and a higher β-amyloid load than ε3ε3.ConclusionAPOE ε2ε4 genotype in older adults is associated with risk of MCI, cognitive decline, and a greater burden of AD pathology, especially β-amyloid.

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Positron emission tomography imaging of serotonin degeneration and beta-amyloid deposition in late-life depression evaluated with multi-modal partial least squares

Translational Psychiatry ◽

10.1038/s41398-021-01539-9 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Gwenn S. Smith ◽

Clifford I. Workman ◽

Hillary Protas ◽

Yi Su ◽

Alena Savonenko ◽

...

Keyword(s):

Depressive Symptoms ◽

Cognitive Decline ◽

Least Squares ◽

Partial Least Squares ◽

Late Life ◽

Beta Amyloid ◽

Healthy Controls ◽

Late Life Depression ◽

Spatial Covariance ◽

Increased Risk

AbstractDepression in late-life is associated with increased risk of cognitive decline and development of all-cause dementia. The neurobiology of late-life depression (LLD) may involve both neurochemical and neurodegenerative mechanisms that are common to depression and dementia. Transgenic amyloid mouse models show evidence of early degeneration of monoamine systems. Informed by these preclinical data, the hypotheses were tested that a spatial covariance pattern of higher beta-amyloid (Aβ) and lower serotonin transporter availability (5-HTT) in frontal, temporal, and parietal cortical regions would distinguish LLD patients from healthy controls and the expression of this pattern would be associated with greater depressive symptoms. Twenty un-medicated LLD patients who met DSM-V criteria for major depression and 20 healthy controls underwent PET imaging with radiotracers for Aβ ([11C]-PiB) and 5-HTT ([11C]-DASB). A voxel-based multi-modal partial least squares (mmPLS) algorithm was applied to the parametric PET images to determine the spatial covariance pattern between the two radiotracers. A spatial covariance pattern was identified, including higher Aβ in temporal, parietal and occipital cortices associated with lower 5-HTT in putamen, thalamus, amygdala, hippocampus and raphe nuclei (dorsal, medial and pontine), which distinguished LLD patients from controls. Greater expression of this pattern, reflected in summary 5-HTT/Aβ mmPLS subject scores, was associated with higher levels of depressive symptoms. The mmPLS method is a powerful approach to evaluate the synaptic changes associated with AD pathology. This spatial covariance pattern should be evaluated further to determine whether it represents a biological marker of antidepressant treatment response and/or cognitive decline in LLD patients.

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Chronic kidney disease biomarkers, cognitive impairment and incident dementia in an older healthy cohort

Kidney360 ◽

10.34067/kid.0005672021 ◽

2021 ◽

pp. 10.34067/KID.0005672021

Author(s):

Anne M. Murray ◽

Le Thi Phuong Thao ◽

Joanne Ryan ◽

Rory Wolfe ◽

James B. Wetmore ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Cognitive Impairment ◽

Kidney Disease ◽

Cognitive Decline ◽

Test Scores ◽

Older Persons ◽

Cognitive Test ◽

Cognitive Tests ◽

Incident Dementia ◽

Increased Risk

Background: Chronic kidney disease is a risk factor for cognitive impairment (CI),but reports of individual associations of estimated glomerular filtration rate (eGFR) and albuminuria with CI and incident dementia in healthier older longitudinal populations are lacking. Our goal was to estimate these associations in a large cohort of older healthy persons. Methods: In a longitudinal cohort study of older persons without prior cardiovascular disease, we estimated the associations between baseline eGFR (in mL/min per 1.73 m2) and albuminuria, measured as urine albumin-to-creatinine ratio (UACR, in mg/mmol) and cognitive test scores, declines in cognitive test scores and incident dementia, using adjusted linear and linear mixed models. Cox proportional hazards regression models assessed the association between baseline kidney function and incident CI no dementia (CIND) or dementia at a median of 4.7 years. Results: At baseline, among 18,131 participants, median age was 74 years, eGFR 74 (IQR 63, 84), UACR 0.8 (IQR 0.5, 1.5; (7.1 (4.4- 13.3 mg/g and 56% were female. Baseline eGFR was not associated with performance on any cognitive tests in cross-sectional analysis, nor incident CIND or dementia over median follow-up of 4.7 years. However, baseline UACR ≥ 3 (≥ 26.6 mg/g) was significantly associated with lower baseline scores and larger declines on the Modified Mini Mental State Exam, verbal memory and processing speed tests, and with incident CIND [(hazard ratio, HR, 1.19; 95% confidence interval, CI,1.07 - 1.33)] and dementia (HR 1.32;1.06 - 1.66). Conclusion: Mild albuminuria was associated with worse baseline cognitive function, cognitive decline, and increased risk for incident CIND and dementia. Screening global cognitive tests for older persons with UACR ≥ 3 mg/mmol could identify those at elevated risk of cognitive decline and dementia.

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