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

2017 ◽  
Vol 30 (7) ◽  
pp. 981-990 ◽  
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.

scholarly journals Individual variation in brain microstructural-cognition relationships in aging

2021 ◽  
Author(s):  
Raihaan Patel ◽  
Clare E. Mackay ◽  
Michelle G. Jansen ◽  
Gabriel A. Devenyi ◽  
M. Clare O’Donoghue ◽  
...  
Keyword(s):  
Cognitive Decline ◽  
Cognitive Performance ◽  
Late Life ◽  
Older Age ◽  
Data Driven ◽  
Semantic Fluency ◽  
Cognitive Domains ◽  
Age Related ◽  
Brain Microstructure ◽  
Age Related Cognitive Decline

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.

Association of Military Employment With Late-Life Cognitive Decline and Dementia: A Population-Based Prospective Cohort Study

2021 ◽  
Author(s):  
Melinda C Power ◽  
Alia E Murphy ◽  
Kan Z Gianattasio ◽  
Y i Zhang ◽  
Rod L Walker ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Cohort Study ◽  
Brain Injury ◽  
Cognitive Decline ◽  
Late Life ◽  
Cognitive Change ◽  
Effect Modification ◽  
Sensitivity Analyses ◽  
Loss Of Consciousness ◽  
Increased Risk

ABSTRACT Introduction As the number of U.S. veterans over age 65 has increased, interest in whether military service affects late-life health outcomes has grown. Whether military employment is associated with increased risk of cognitive decline and dementia remains unclear. Materials and Methods We used data from 4,370 participants of the longitudinal Adult Changes in Thought (ACT) cohort study, enrolled at age 65 or older, to examine whether military employment was associated with greater cognitive decline or higher risk of incident dementia in late life. We classified persons as having military employment if their first or second-longest occupation was with the military. Cognitive status was assessed at each biennial Adult Changes in Thought study visit using the Cognitive Abilities Screening Instrument, scored using item response theory (CASI-IRT). Participants meeting screening criteria were referred for dementia ascertainment involving clinical examination and additional cognitive testing. Primary analyses were adjusted for sociodemographic characteristics and APOE genotype. Secondary analyses additionally adjusted for indicators of early-life socioeconomic status and considered effect modification by age, gender, and prior traumatic brain injury with loss of consciousness TBI with LOC. Results Overall, 6% of participants had military employment; of these, 76% were males. Military employment was not significantly associated with cognitive change (difference in modeled 10-year cognitive change in CASI-IRT scores in SD units (95% confidence interval [CI]): −0.042 (−0.19, 0.11), risk of dementia (hazard ratio [HR] [95% CI]: 0.92 [0.71, 1.18]), or risk of Alzheimer’s disease dementia (HR [95% CI]: 0.93 [0.70, 1.23]). These results were robust to additional adjustment and sensitivity analyses. There was no evidence of effect modification by age, gender, or traumatic brain injury with loss of consciousness. Conclusions Among members of the Adult Changes in Thought cohort, military employment was not associated with increased risk of cognitive decline or dementia. Nevertheless, military veterans face the same high risks for cognitive decline and dementia as other aging adults.

scholarly journals Prescription Medications and Co-Morbidities in Late Middle-Age are Associated with Greater Cognitive Declines: Results from WRAP

2022 ◽  
Vol 2 ◽  
Author(s):  
Lianlian Du ◽  
Rebecca Langhough Koscik ◽  
Nathaniel A. Chin ◽  
Lisa C. Bratzke ◽  
Karly Cody ◽  
...  
Keyword(s):  
Executive Function ◽  
Cognitive Performance ◽  
Repeated Measures ◽  
Cognitive Change ◽  
Cognitive Domain ◽  
Objective Measures ◽  
Mixed Effect ◽  
Health History ◽  
Age Related ◽  
Increased Risk

The present study investigated: 1) sex differences in polypharmacy, comorbidities, self-rated current health (SRH), and cognitive performance, 2) associations between comorbidities, polypharmacy, SRH, and objective measures of health, and 3) associations of these factors with longitudinal cognitive performance. Analyses included 1039 eligible Wisconsin Registry for Alzheimer’s Prevention (WRAP) participants who were cognitively unimpaired at baseline and had ≥2 visits with cognitive composites, self-reported health history, and concurrent medication records. Repeated measures correlation (rmcorr) examined the associations between medications, co-morbidities, SRH, and objective measures of health (including LIfestyle for BRAin Health Index (LIBRA), and depression). Linear mixed-effect models examined associations between medications, co-morbidities, and cognitive change over time using a preclinical Alzheimer’s cognitive composite (PACC3) and cognitive domain z-scores (executive function, working memory, immediate learning, and delayed recall). In secondary analyses, we also examined whether the number of medications interacted with co-morbidities and whether they modified age-related cognitive trajectories. The number of prescribed medications was associated with worse SRH and a higher number of self-reported co-morbidities. More prescribed medications were associated with a faster decline in executive function, and more comorbidities were associated with faster PACC3 decline. Those with a non-elevated number of co-morbidities and medications performed an average of 0.26 SD higher (better) in executive function and an average of 0.18 SD higher on PACC3 than those elevated on both. Associations between medications, co-morbidities, and executive function, and PACC3 suggest that persons with more co-morbidities and medications may be at increased risk of reaching clinical levels of impairment earlier than healthier, less medicated peers.

scholarly journals Multimodal measurement approach to identify individuals with mild cognitive impairment: study protocol for a cross-sectional trial

BMJ Open ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. e046879
Author(s):  
Bernhard Grässler ◽  
Fabian Herold ◽  
Milos Dordevic ◽  
Tariq Ali Gujar ◽  
Sabine Darius ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Statistical Analysis ◽  
Cognitive Decline ◽  
Cognitive Performance ◽  
Classification Accuracy ◽  
Multimodal Approach ◽  
Cross Sectional ◽  
Age Related ◽  
Age Related Cognitive Decline

IntroductionThe diagnosis of mild cognitive impairment (MCI), that is, the transitory phase between normal age-related cognitive decline and dementia, remains a challenging task. It was observed that a multimodal approach (simultaneous analysis of several complementary modalities) can improve the classification accuracy. We will combine three noninvasive measurement modalities: functional near-infrared spectroscopy (fNIRS), electroencephalography and heart rate variability via ECG. Our aim is to explore neurophysiological correlates of cognitive performance and whether our multimodal approach can aid in early identification of individuals with MCI.Methods and analysisThis study will be a cross-sectional with patients with MCI and healthy controls (HC). The neurophysiological signals will be measured during rest and while performing cognitive tasks: (1) Stroop, (2) N-back and (3) verbal fluency test (VFT). Main aims of statistical analysis are to (1) determine the differences in neurophysiological responses of HC and MCI, (2) investigate relationships between measures of cognitive performance and neurophysiological responses and (3) investigate whether the classification accuracy can be improved by using our multimodal approach. To meet these targets, statistical analysis will include machine learning approaches.This is, to the best of our knowledge, the first study that applies simultaneously these three modalities in MCI and HC. We hypothesise that the multimodal approach improves the classification accuracy between HC and MCI as compared with a unimodal approach. If our hypothesis is verified, this study paves the way for additional research on multimodal approaches for dementia research and fosters the exploration of new biomarkers for an early detection of nonphysiological age-related cognitive decline.Ethics and disseminationEthics approval was obtained from the local Ethics Committee (reference: 83/19). Data will be shared with the scientific community no more than 1 year following completion of study and data assembly.Trial registration numberClinicalTrials.gov, NCT04427436, registered on 10 June 2020, https://clinicaltrials.gov/ct2/show/study/NCT04427436.

Bidirectional Association Between Depression and Hearing Loss: Evidence From the China Health and Retirement Longitudinal Study

2021 ◽  
pp. 073346482110423
Author(s):  
Chao Wu
Keyword(s):  
Hearing Loss ◽  
Longitudinal Study ◽  
Cognitive Decline ◽  
Age Related ◽  
Bidirectional Association ◽  
Health Related ◽  
Clinically Significant ◽  
Using Data ◽  
Bidirectional Associations ◽  
Age Related Hearing Loss

The relationship between depression and age-related hearing loss (ARHL) is not fully understood. This study tested the bidirectional associations between clinically significant depressive symptoms (CSDSs) and ARHL in middle-aged and older adults using data from the China Health and Retirement Longitudinal Study. Among 3,418 participants free of baseline ARHL, baseline CSDS was associated with an increased odds of incident ARHL (odds ratio [OR]: 1.51). Cognitive decline, BMI, and arthritis partially mediated the longitudinal CSDS–ARHL association and explained 24% of the variance in the total effect. Among 4,921 participants without baseline CSDS, baseline ARHL was associated with an increased odds of incident CSDS (OR: 1.37). The bidirectional associations remained significant after adjustments for baseline demographic factors, comorbidities, and other health-related covariates. Depression may contribute to the development of ARHL, and vice versa. Interventions in depression, cognitive decline, and arthritis may delay the onset of ARHL and break the vicious circle between them.

scholarly journals Do social factors mediate or moderate the sensory-cognitive associations in older adults in the Canadian Longitudinal Study on Aging?

2019 ◽  
Author(s):  
Anni Hämäläinen ◽  
Natalie Phillips ◽  
Walter Wittich ◽  
Paul Mick ◽  
M Kathleen Pichora-Fuller
Keyword(s):  
Longitudinal Study ◽  
Cognitive Decline ◽  
Social Factors ◽  
Pure Tone Audiometry ◽  
Sensory Function ◽  
Sensory Loss ◽  
Protective Effects ◽  
Social Variables ◽  
Cross Sectional ◽  
Age Related

Sensory and cognitive function both tend to decline with increasing age. Sensory impairments are risk factors for age-related cognitive decline and dementia. One hypothesis about sensory-cognitive associations is that sensory loss results in social isolation which, in turn, is a risk factor for cognitive decline. We tested whether social factors are associated with cognitive and sensory function, and whether sensory-cognitive associations are mediated or moderated by social factors. We used cross-sectional data from 30,029 participants in the Canadian Longitudinal Study of Aging, aged 45-85 years, who had no reported cognitive impairment or diagnosis of dementia. We found strong independent associations of self-reported social variables with hearing (pure-tone audiometry), vision (pinhole-corrected visual acuity), and executive function and weaker associations with memory. The moderating and mediating effects of social variables on sensory-cognitive associations were weak and mostly non-significant, but social factors could be slightly more important for females and older people. Partial retirement (relative to full retirement or not being retired) may have protective effects on cognition in the presence of hearing loss. These findings confirm the association between social factors and sensory and cognitive measures. However, support is weak for the hypothesis that social factors shape sensory-cognitive associations.

scholarly journals Subtypes of Late-Life Depression: A Data-Driven Approach on Cognitive Domains and Physical Frailty

2020 ◽  
Vol 76 (1) ◽  
pp. 141-150 ◽  
Author(s):  
Astrid Lugtenburg ◽  
Marij Zuidersma ◽  
Klaas J Wardenaar ◽  
Ivan Aprahamian ◽  
Didi Rhebergen ◽  
...  
Keyword(s):  
Depressive Symptom ◽  
Cognitive Performance ◽  
Latent Profile Analysis ◽  
Profile Analysis ◽  
Late Life ◽  
Late Life Depression ◽  
Physical Frailty ◽  
Cognitive Domains ◽  
Age Related ◽  
Latent Profile

Abstract Background With increasing age, symptoms of depression may increasingly overlap with age-related physical frailty and cognitive decline. We aim to identify late-life-related subtypes of depression based on measures of depressive symptom dimensions, cognitive performance, and physical frailty. Methods A clinical cohort study of 375 depressed older patients with a DSM-IV depressive disorder (acronym NESDO). A latent profile analysis was applied on the three subscales of the Inventory of Depressive Symptomatology, as well as performance in five cognitive domains and two proxies for physical frailty. For each class, we investigated remission, dropout, and mortality at 2-year follow-up as well as change over time of depressive symptom severity, cognitive performance, and physical frailty. Results A latent profile analysis model with five classes best described the data, yielding two subgroups suffering from pure depression (“mild” and “severe” depression, 55% of all patients) and three subgroups characterized by a specific profile of cognitive and physical frailty features, labeled as “amnestic depression,” “frail-depressed, physically dominated,” and “frail-depressed, cognitively dominated.” The prospective analyses showed that patients in the subgroup of “mild depression” and “amnestic depression” had the highest remission rates, whereas patients in both frail-depressed subgroups had the highest mortality rates. Conclusions Late-life depression can be subtyped by specific combinations of age-related clinical features, which seems to have prospective relevance. Subtyping according to the cognitive profile and physical frailty may be relevant for studies examining underlying disease processes as well as to stratify treatment studies on the effectiveness of antidepressants, psychotherapy, and augmentation with geriatric rehabilitation.

scholarly journals Early-Life Exposure to the Chinese Famine and Risk of Cognitive Decline

2019 ◽  
Vol 8 (4) ◽  
pp. 484 ◽  
Author(s):  
Hongguo Rong ◽  
Xiaozhen Lai ◽  
Elham Mahmoudi ◽  
Hai Fang
Keyword(s):  
Cognitive Decline ◽  
Cognitive Performance ◽  
Early Life ◽  
Late Life ◽  
Cognitive Status ◽  
Word Recall ◽  
Long Term Effects ◽  
Negative Effects ◽  
Multi Stage ◽  
Famine Exposure

Previous studies on the Chinese famine suggested long-term effects of early-life famine exposure on health conditions. This study aims to investigate the association between exposure to the Chinese famine of 1959–1961 at different early-life stages and the risk of cognitive decline in adulthood. A total of 6417 adults born between 1952 and 1964 in the 2015 survey data of China Health and Retirement Longitudinal Study were included in this study. Cognitive performance was estimated through a series of comprehensive neuropsychological tests, including the Telephone Interview of Cognitive Status (TICS-10), word recall, and pentagon drawing. Multiple generalized linear model (GLM) was employed to detect the association between multi-stage early-life famine exposure and late-life cognitive performance. Compared with the unexposed group, respondents exposed to famine in the fetal period performed worse in the TICS (difference −0.52, 95% confidence interval (CI): −0.93 to −0.10), word recall (difference −0.46, 95% CI: −0.74 to −0.19), and general cognition (difference −1.05, 95% CI: −1.64 to −0.47). Furthermore, we also found negative effects of famine exposure on performance of word recall and pentagon drawing in the early (word recall difference −0.56, 95% CI: −1.00 to −0.11; pentagon drawing difference −0.76, 95% CI: −1.40 to −0.12), mid (word recall difference −0.46, 95% CI: −0.81 to −0.11; pentagon drawing difference −0.66, 95% CI: −1.16 to −0.16), and late (word recall difference −0.30, 95% CI: −0.55 to −0.04; pentagon drawing difference −0.75, 95% CI: −1.13 to −0.37) childhood-exposed groups. Early-life famine exposure in different stages is positively associated with late-life cognitive decline. Fetal famine exposure might affect the overall cognitive status in adulthood, and childhood famine exposure has potential adverse effects on visuospatial episodic memory.

scholarly journals PARASYMPATHETIC INFLUENCE ON COGNITIVE AGING IS MODERATED BY SYMPATHETIC ACTIVITY, ESPECIALLY IN EARLY MIDLIFE

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S94-S94 ◽  
Author(s):  
Erik L Knight ◽  
Ryan Giuliano ◽  
Sean Shank ◽  
Megan Clarke ◽  
David M Almeida
Keyword(s):  
Nervous System ◽  
Cognitive Decline ◽  
Cognitive Aging ◽  
Parasympathetic Nervous System ◽  
Cognitive Change ◽  
Interactive Effects ◽  
Cognitive Test ◽  
Cognitive Changes ◽  
Beneficial Effects ◽  
Age Related

Abstract The two branches of the autonomic nervous system (ANS) have been individually linked to age-related changes in cognitive functioning: The parasympathetic nervous system (PNS) is thought to support healthy cognitive aging, whereas the sympathetic nervous system (SNS) has been linked to heightened cognitive decline. Despite these separate findings and despite the integrative nature of the ANS, little work has examined the two branches simultaneously to better understand their interactive effects on age-related cognitive changes. We examined cognitive change in two waves of the MIDUS cognitive project and indexed PNS and SNS activity from heart rate variability and epinephrine levels (respectively) from the MIDUS biomarker project (n = 764, 56% female, mean age = 54.1 years). Our findings indicate that higher PNS levels attenuate cognitive decline, but only among individuals with low SNS levels; at higher SNS levels, the beneficial effects of the PNS are blocked. Further, lower PNS levels can be somewhat compensated for by increased SNS levels. This pattern was most robust among individuals transitioning to mid-life (i.e., 35-40 years old at the initial cognitive test). These results suggest that interventions targeting the ANS as a modifiable factor in cognitive aging should consider both ANS branch’s effects simultaneously, particularly in the early stages of midlife.

Do cognitive complaints either predict future cognitive decline or reflect past cognitive decline? A longitudinal study of an elderly community sample

1997 ◽  
Vol 27 (1) ◽  
pp. 91-98 ◽  
Author(s):  
A. F. JORM ◽  
H. CHRISTENSEN ◽  
A. E. KORTEN ◽  
A. S. HENDERSON ◽  
P. A. JACOMB ◽  
...  
Keyword(s):  
Longitudinal Study ◽  
Cognitive Decline ◽  
Mini Mental State Examination ◽  
Community Sample ◽  
Cognitive Change ◽  
Cognitive Disorder ◽  
Anxiety And Depression ◽  
Cognitive Complaints ◽  
Cognitive Changes ◽  
State Examination

Data from a two-wave longitudinal study of an elderly community sample were used to assess whether cognitive complaints either predict subsequent cognitive decline or reflect past cognitive decline. Cognitive complaints and cognitive functioning were assessed on two occasions three and a half years apart. Cognitive complaints at Wave 1 were found not to predict future cognitive change on the Mini-Mental State Examination, an episodic memory test or a test of mental speed. Similarly, cognitive complaints at Wave 2 were unrelated to past cognitive changes on these tests after statistically controlling for the effects of anxiety and depression. Furthermore, cognitive complaints did not predict either mortality (after controlling for anxiety and depression) or future dementia. These results are evidence against the inclusion of cognitive complaints in diagnostic criteria for proposed disorders such as age-associated memory impairment, mild cognitive disorder and ageing-associated cognitive decline.

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