Depressive symptoms are associated with late life cognitive decline independent of common age-related pathologies

AbstractWhile all individuals are susceptible to age-related cognitive decline, significant inter- and intra-individual variability exists. However, the sources of this variation remain poorly understood. Here, we examined the association between 30-year trajectories of cognitive decline and multimodal indices of brain microstructure and morphology in older age. We used the Whitehall II Study, an extensively characterised cohort using 3T brain magnetic resonance images acquired at older age (mean age = 69.52 ± 4.9) and 5 repeated cognitive performance assessments between mid-life (mean age = 53.2 ± 4.9 years) and late-life (mean age = 67.7 ± 4.9). Using non-negative matrix factorization, we identified 10 brain microstructural components that integrate measures of cortical thickness, surface area, fractional anisotropy, and mean and radial diffusivities. We observed two modes of variance that describe the association between cognition and brain microstructure. The first describes variations in 5 microstructural components associated with low mid-life performance across multiple cognitive domains, decline in reasoning abilities, but a relative maintenance of lexical and semantic fluency from mid-to-late life. The second describes variations in 5 microstructural components that are associated with low mid-life performance in lexical fluency, semantic fluency and short-term memory performance, but a retention of abilities in multiple domains from mid-to-late life. The extent to which a subject loads onto a latent variables predicts their future cognitive performance 3.2 years later (mean age = 70.87 ± 4.9). This data-driven approach highlights a complex pattern of brain-behavior relationships, wherein the same individuals express both decline and maintenance in function across cognitive domains and in brain structural features.Significance StatementAlthough declines in cognitive performance are an established aspect of aging, inter- and intra-individual variation exists. Nevertheless, the sources of this variation remain unclear. We analyse a unique sample to examine associations between 30-year trajectories of cognitive decline and multimodal indices of brain anatomy in older age. Using data-driven techniques, we find that age-related cognitive decline is not uniform. Instead, each individual expresses a mixture of maintenance and decline across cognitive domains, that are associated with a mixture of preservation and degeneration of brain structure. Further, we find the primary determinants of late-life cognitive performance are mid-life performance and higher brain surface area. These results suggest that early and mid-life preventative measures may be needed to reduce age-related cognitive decline.

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P1-118: The Tasmanian Healthy Brain Study (THBS): Does late-life education prevent age-related cognitive decline and dementia?

Alzheimer s & Dementia ◽

10.1016/j.jalz.2012.05.395 ◽

2012 ◽

Vol 8 (4S_Part_4) ◽

pp. P147-P147

Author(s):

Mathew Summers ◽

Michael Valenzuela ◽

Jeffery Summers ◽

Karen Ritchie ◽

Tracey Dickson ◽

...

Keyword(s):

Cognitive Decline ◽

Late Life ◽

Age Related ◽

Life Education ◽

Age Related Cognitive Decline ◽

Brain Study

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O4-08-06: To what extent do common, age-related pathologies contribute to late life cognitive decline?

Alzheimer s & Dementia ◽

10.1016/j.jalz.2013.04.382 ◽

2013 ◽

Vol 9 ◽

pp. P699-P700

Author(s):

Patricia Boyle ◽

Robert Wilson ◽

Lei Yu ◽

Julie Schneider ◽

David Bennett

Keyword(s):

Cognitive Decline ◽

Late Life ◽

Age Related

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Gamma-Glutamyltransferase (GGT) as a biomarker of cognitive decline at the end of life: contrasting age and time to death trajectories

International Psychogeriatrics ◽

10.1017/s1041610217002393 ◽

2017 ◽

Vol 30 (7) ◽

pp. 981-990 ◽

Cited By ~ 6

Author(s):

Marcus Praetorius Björk ◽

Boo Johansson

Keyword(s):

Longitudinal Study ◽

Cognitive Decline ◽

Cognitive Performance ◽

Late Life ◽

Cognitive Change ◽

Gamma Glutamyltransferase ◽

Time To Death ◽

Age Related ◽

Increased Risk ◽

Underlying Mechanisms

ABSTRACTBackground:A recently published study suggests that Gamma-Glutamyltransferase (GGT) in midlife is related to an increased risk of dementia. In the present longitudinal study, we explore the effects of serum GGT on cognitive decline and dementia also in more advanced ages.Methods:We analyzed GGT in a sample of 452 individuals, aged 80 years and older at baseline, with the purpose to explore subsequent effects on cognitive performance. We specifically modeled GGT to cognitive change, time to death, and dementia.Results:Our main finding is that a higher level of GGT is associated with cognitive decline prior to death and vascular dementia in late life. These findings were evident across cognitive domains.Conclusions:This is the first longitudinal study to report on significant associations in late life between GGT, cognitive performance and dementia. Further research is needed to examine the underlying mechanisms of GGT as a marker of age-related cognitive decline.

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Depressive Symptoms Imputed Across the Life Course Are Associated with Cognitive Impairment and Cognitive Decline

Journal of Alzheimer s Disease ◽

10.3233/jad-210588 ◽

2021 ◽

pp. 1-11

Author(s):

Willa D. Brenowitz ◽

Adina Zeki Al Hazzouri ◽

Eric Vittinghoff ◽

Sherita H. Golden ◽

Annette L. Fitzpatrick ◽

...

Keyword(s):

Cognitive Impairment ◽

Depressive Symptoms ◽

Life Course ◽

Cognitive Decline ◽

Early Adulthood ◽

Adult Life ◽

Late Life ◽

Cognitive Outcomes ◽

Life Stages ◽

The Life Course

Background: Depressive symptoms may increase risk for dementia, but findings are controversial because late-life depression may be a prodromal dementia symptom. Life course data on depression and dementia risk may clarify this association; however, data is limited. Objective: To impute adult depressive symptoms trajectories across adult life stages and estimate the association with cognitive impairment and decline. Methods: Using a pooled study of 4 prospective cohorts (ages 20–89), we imputed adult life course depressive symptoms trajectories based on Center for Epidemiologic Studies Depression Scale-10 (CESD-10) and calculated time-weighted averages for early adulthood (ages 20–49), mid-life (ages 50–69), and late-life (ages 70–89) for 6,122 older participants. Adjusted pooled logistic and mixed-effects models estimated associations of imputed depressive symptoms with two cognitive outcomes: cognitive impairment defined by established criteria and a composite cognitive score. Results: In separate models, elevated depressive symptoms in each life stage were associated with cognitive outcomes: early adulthood OR for cognitive impairment = 1.59 (95%CI: 1.35,1.87); mid-life OR = 1.94 (95%CI:1.16, 3.26); and late-life OR = 1.77 (95%CI:1.42, 2.21). When adjusted for depressive symptoms in the other life-stages, elevated depressive symptoms in early adulthood (OR = 1.73; 95%CI: 1.42,2.11) and late-life (OR = 1.43; 95%CI: 1.08,1.89) remained associated with cognitive impairment and were also associated with faster rates of cognitive decline (p < 0.05). Conclusion: Imputing depressive symptom trajectories from pooled cohorts may help expand data across the life course. Our findings suggest early adulthood depressive symptoms may be a risk factor for cognitive impairment independent of mid- or late-life depressive symptoms.

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Limbic-predominant age-related TDP-43 encephalopathy, ADNC pathology, and cognitive decline in aging

Neurology ◽

10.1212/wnl.0000000000010454 ◽

2020 ◽

Vol 95 (14) ◽

pp. e1951-e1962

Author(s):

Alifiya Kapasi ◽

Lei Yu ◽

Patricia A. Boyle ◽

Lisa L. Barnes ◽

David A. Bennett ◽

...

Keyword(s):

Alzheimer Disease ◽

Cognitive Decline ◽

Late Life ◽

Cognitive Testing ◽

Mixed Effect ◽

Mixed Effect Models ◽

Age Related ◽

Global Cognition ◽

Rate Of Decline ◽

The Impact

ObjectiveTo examine the impact of 3 pathologic groups, pure limbic-predominant age-related transactive response DNA-binding protein 43 encephalopathy (LATE) neuropathologic changes (NC), pure Alzheimer disease neuropathologic change (ADNC), and mixed ADNC with LATE-NC, on late-life cognitive decline.MethodsData came from 1,356 community-based older persons who completed detailed annual cognitive testing and systematic neuropathologic examination at autopsy to identify LATE-NC, ADNC, and other age-related pathologies. Persons were categorized into (0) a group without a pathologic diagnosis of LATE or ADNC (n = 378), (1) LATE-NC without ADNC (n = 91), (2) ADNC without LATE-NC (n = 535), and (3) mixed ADNC with LATE-NC (n = 352). We used mixed-effect models to examine the group associations with rate of decline in global cognition and 5 cognitive domains and then examined whether age modified associations.ResultsCompared to those without LATE-NC or ADNC, those with pure LATE-NC had a faster decline in global cognition (p = 0.025) and episodic memory (p = 0.002); however, compared to persons with pure ADNC, those with pure LATE-NC showed a slower decline. Those with mixed ADNC with LATE-NC showed the fastest decline compared to those with either pathology alone. Persons ≥90 years of age with mixed ADNC with LATE-NC had slower cognitive decline compared to those ≤89 years of age.ConclusionPersons with pure LATE-NC follow a slower trajectory compared to those with pure ADNC. Those with mixed LATE/ADNC have a steeper decline than individuals with either pathology alone. In addition, age may modify the effect of pathology on cognitive decline. These findings have important implications for the development of biomarkers and prognosis for late-life cognitive decline.Classification of evidenceThis study provides Class I evidence that LATE-NC and Alzheimer disease pathologic changes are associated with different trajectories of late-life cognitive decline.

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AGE-RELATED HEARING LOSS AS A RISK FACTOR FOR LATE LIFE DEPRESSION AND COGNITIVE DECLINE

American Journal of Geriatric Psychiatry ◽

10.1016/j.jagp.2019.01.195 ◽

2019 ◽

Vol 27 (3) ◽

pp. S43-S44

Author(s):

Anu Sharma ◽

Bret R Rutherford ◽

Frank Lin ◽

Justin Scott Golub ◽

Katharine Kim Brewster

Keyword(s):

Hearing Loss ◽

Risk Factor ◽

Cognitive Decline ◽

Late Life ◽

Late Life Depression ◽

Age Related ◽

Age Related Hearing Loss

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Sensation and Psychiatry: Linking Age-Related Hearing Loss to Late-Life Depression and Cognitive Decline

American Journal of Psychiatry ◽

10.1176/appi.ajp.2017.17040423 ◽

2018 ◽

Vol 175 (3) ◽

pp. 215-224 ◽

Cited By ~ 77

Author(s):

Bret R. Rutherford ◽

Katharine Brewster ◽

Justin S. Golub ◽

Ana H. Kim ◽

Steven P. Roose

Keyword(s):

Hearing Loss ◽

Cognitive Decline ◽

Late Life ◽

Late Life Depression ◽

Age Related ◽

Age Related Hearing Loss

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Nine-Year Ethanol Intake Trajectories and Their Association With 15-Year Cognitive Decline Among Black and White Adults

American Journal of Epidemiology ◽

10.1093/aje/kwaa006 ◽

2020 ◽

Vol 189 (8) ◽

pp. 788-800

Author(s):

Shelly-Ann M Love ◽

Kari E North ◽

Donglin Zeng ◽

Natalia Petruski-Ivleva ◽

Anna Kucharska-Newton ◽

...

Keyword(s):

Cognitive Decline ◽

Heavy Drinking ◽

Late Life ◽

Ethanol Intake ◽

Linear Regression Models ◽

Atherosclerosis Risk In Communities ◽

Moderate Drinking ◽

Black And White ◽

Age Related ◽

White Adults

Abstract Faster rates of age-related cognitive decline might result in early onset of cognitive impairment and dementia. The relationship between ethanol intake and cognitive decline, although studied extensively, remains poorly understood. Previous studies used single measurements of ethanol, and few were conducted in diverse populations. We assessed the association of 9-year trajectories of ethanol intake (1987–1998) with 15-year rate of decline in cognitive performance from mid- to late life (1996–2013) among 2,169 Black and 8,707 White participants of the US Atherosclerosis Risk in Communities study using multivariable linear regression models. We hypothesized that stable, low to moderate drinking would be associated with lesser 15-year cognitive decline, and stable, heavy drinking with greater 15-year cognitive decline. Stable, low to moderate drinking (for Blacks, adjusted mean difference (MD) = 0.03 (95% confidence interval (CI): −0.13, 0.19); for Whites, adjusted MD = 0.02 (95% CI: −0.05, 0.08)) and stable, heavy drinking (for Blacks, adjusted MD = 0.08 (95% CI: −0.34, 0.50); for Whites, adjusted MD = −0.03 (95% CI: −0.18, 0.11)) in midlife compared with stable never-drinking were not associated with 15-year decline in general cognitive function from mid- to late life. No association was observed for the stable former and “mostly” drinking trajectories with 15-year cognitive decline. Stable low, low to moderate, and stable heavy drinking in midlife are not associated with lesser and greater cognitive decline, respectively, from mid- to late life among Black and White adults.

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