APOE E2/E2 Is Associated with Slower Rate of Cognitive Decline with Age

2021 ◽  
pp. 1-8
Author(s):  
Benjamin Sweigart ◽  
Stacy L. Andersen ◽  
Anastasia Gurinovich ◽  
Stephanie Cosentino ◽  
Nicole Schupf ◽  
...  
Keyword(s):  
Cognitive Function ◽  
Protective Effect ◽  
Cognitive Decline ◽  
New England ◽  
Secondary Analysis ◽  
Cognitive Change ◽  
Cognitive Status ◽  
Mixed Effect ◽  
Rate Of Decline ◽  
Apoe Genotypes

Background: The E4 allele of the APOE gene is known to be associated with cognitive impairment. However, a limited number of studies have examined the association between the E2 allele and longitudinal changes of cognitive function. Objective: To determine whether rates of cognitive change differ in carriers of the APOE E2 allele compared to other genotypes. Methods: We conducted a secondary analysis of data from two ongoing longitudinal cohort studies, the Long Life Family Study (LLFS) and New England Centenarian Study (NECS). We included participants who had APOE genotyping data, data from longitudinal administrations of the Telephone Interview for Cognitive Status (TICS), and age, sex, and education available. We assessed whether cognitive change as measured by rate of decline in TICS score differed among people with different APOE genotypes. We used a hierarchical mixed effect model with APOE genotypes, their interactions with age, and potential confounders. Results: After adjusting for sex and education, in carriers of the common E3/E3 genotype, TICS score decreased by 0.15 points per year of age. In those with the E2/E2 genotype, TICS score decreased by 0.05 points per year of age, a significantly slower rate of decline (p = 0.017). We observed no protective effect of the E2/E3 genotype on cognitive decline. Conclusion: These results suggest a protective effect of the E2/E2 genotype on a measure of global cognitive function.

scholarly journals REDUCED COGNITIVE DECLINE WITH THE APOE ε2/ε2 GENOTYPE IN THE LONG LIFE FAMILY STUDY AND NEW ENGLAND CENTENARIAN STUDY

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S621-S621
Author(s):  
Benjamin Sweigart ◽  
Benjamin Sweigart ◽  
Stacy L Andersen ◽  
Stephanie Cosentino ◽  
Nicole Schupf ◽  
...  
Keyword(s):  
Protective Effect ◽  
Cognitive Decline ◽  
New England ◽  
Repeated Measures ◽  
Family Study ◽  
Reference Group ◽  
Cognitive Status ◽  
P Value ◽  
Long Life ◽  
Rate Of Decline

Abstract A growing body of evidence has suggested a protective effect on cognition of the ε2 allele of APOE. To determine if APOE ε2 is associated with protection against cognitive decline, we analyzed repeated measures of the Telephone Interview for Cognitive Status (TICS) from 2,933 Long Life Family Study subjects and 679 New England Centenarian Study subjects using a multivariable linear mixed effects model. The median age at first TICS administration was 73 (interquartile range [IQR] 64, 83). Subjects had a median of 3 TICS assessments (IQR 2, 4) and a median follow-up time of 5.0 years (IQR 2.9, 7.0). Carriers of the ε2/ε2 genotype had a significantly slower rate of decline in TICS score compared to the ε3/ε3 reference group (-0.05 points per annum for ε2/ε2 carriers compared with -0.15 points for ε3/ε3 carriers, p-value for difference 0.017). These results support a protective effect of the ε2 allele.

Investigating walnut consumption and cognitive trajectories in a representative sample of older US adults

2020 ◽  
pp. 1-12
Author(s):  
Nicholas J Bishop ◽  
Krystle E Zuniga
Keyword(s):  
Older Adults ◽  
Cognitive Function ◽  
Representative Sample ◽  
Secondary Analysis ◽  
Health Behaviours ◽  
Cognitive Change ◽  
Cognitive Status ◽  
Sensitivity Analyses ◽  
Age Related ◽  
The Usa

Abstract Objective: Existing research suggests walnut intake may be associated with better cognitive function in older adults, yet few studies utilise longitudinal data from observational studies of ageing populations. Our objective was to estimate the association between whole walnut intake and cognitive change in a representative sample of older Americans. Design: Secondary analysis of the Health and Retirement Study and Health Care and Nutrition Study. Walnut consumption was defined as a categorical measure (none, low intake (0·01–0·08 1 oz. servings per day) and moderate intake (>0·08 1 oz. servings per day)) and cognitive function was measured using the Telephone Interview for Cognitive Status. Latent growth modelling estimated the association between walnut consumption and trajectories of cognitive status over a 4-year observational period. Sensitivity analyses assessing non-random dropout and Monte Carlo power analyses were conducted to contextualise results. Setting: The USA. Participants: A sample of 3632 US adults aged 65 years and older. Results: Those reporting any walnut consumption had greater cognitive scores at baseline than those not consuming walnuts (low walnut consumption, b = 1·53, se = 0·21, P < 0·001; moderate walnut consumption, b = 2·22, se = 0·27, P < 0·001), but walnut consumption was not associated with cognitive change. Walnut consumption was positively associated with socioeconomic status and health behaviours as well as intake of nutrients identified to have neuroprotective benefits. Conclusions: We identified an association between walnut consumption and cognitive function in older adults, although we did not find that walnut consumption was protective against age-related cognitive decline.

One size fits all? Why we need more sophisticated analytical methods in the explanation of trajectories of cognition in older age and their potential risk factors

2009 ◽  
Vol 22 (2) ◽  
pp. 291-299 ◽  
Author(s):  
Graciela Muniz Terrera ◽  
Carol Brayne ◽  
Fiona Matthews ◽  
Keyword(s):  
Risk Factors ◽  
Cognitive Impairment ◽  
Cognitive Decline ◽  
Potential Risk ◽  
Analytical Methods ◽  
Cognitive Change ◽  
Population Based ◽  
Growth Mixture ◽  
Potential Risk Factors ◽  
Rate Of Decline

ABSTRACTBackground: Cognitive decline in old age varies among individuals. The identification of groups of individuals with similar patterns of cognitive change over time may improve our ability to see whether the effect of risk factors is consistent across groups.Methods: Whilst accounting for the missing data, growth mixture models (GMM) were fitted to data from four interview waves of a population-based longitudinal study of aging, the Cambridge City over 75 Cohort Study (CC75C). At all interviews global cognition was assessed using the Mini-mental State Examination (MMSE).Results: Three patterns were identified: a slow decline with age from a baseline of cognitive ability (41% of sample), an accelerating decline from a baseline of cognitive impairment (54% of sample) and a steep constant decline also from a baseline of cognitive impairment (5% of sample). Lower cognitive scores in those with less education were seen at baseline for the first two groups. Only in those with good performance and steady decline was the effect of education strong, with an increased rate of decline associated with poor education. Good mobility was associated with higher initial score in the group with accelerating change but not with rate of decline.Conclusion: Using these analytical methods it is possible to detect different patterns of cognitive change with age. In this investigation the effect of education differs with group. To understand the relationship of potential risk factors for cognitive decline, careful attention to dropout and appropriate analytical methods, in addition to long-term detailed studies of the population points, are required.

scholarly journals Transforming Aging: Increased Access to Care Minimizes Rural and Urban Differences in Cognitive Change

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 482-483
Author(s):  
Timothy Ly ◽  
Rebecca Allen ◽  
Barbara Jackson ◽  
Amy Albright ◽  
John Bell ◽  
...  
Keyword(s):  
Older Adults ◽  
Health Outcomes ◽  
Cognitive Decline ◽  
Access To Care ◽  
Behavioral Health ◽  
Urban Areas ◽  
Cognitive Change ◽  
Cognitive Status ◽  
Cognitive Health ◽  
Rural And Urban

Abstract Rural-urban disparities in cognitive health outcomes, such as greater prevalence of cognitive decline among rural-dwelling older adults, have been linked to inequity in access to care. However, few studies have demonstrated whether longitudinal increased access to care may mitigate such disparities. This paper presents data from ongoing systematically collected behavioral health data on new and returning patients at an interdisciplinary geriatrics clinic at the University of Alabama Medical Center. The aim of this study was to determine baseline predictors of cognitive change across three annual visits (n = 42, mean age of 75.63 years (SD = 9.15)). Adjusting for baseline cognitive status, baseline subjective health literacy, and baseline depression and anxiety, results from a univariate ANCOVA showed that age at first visit (B = -.024, 95% CI [-.041, -.008], t(35) = -2.990, p = .005) and rural-urban status (B = .555, 95% CI [.123, .988], t(35) = 2.608, p = .013) predicted cognitive change at timepoint three (T3). Specifically, individuals from rural areas were less likely to experience cognitive decline and scored .555 points better than individuals from urban areas on cognitive screeners at T3 compared with baseline cognitive status. These results suggest that increased access to and utilization of care may ameliorate traditional disparate rates of cognitive decline between rural- and urban-dwelling older adults. Moreover, behavioral health screenings in primary geriatrics clinic care may help identify patient cognitive needs and facilitate integrated care through combined medical, pharmacological, and behavioral interventions to promote positive cognitive health outcomes.

scholarly journals Plasma Glutathione Levels Decreased with Cognitive Decline among People with Mild Cognitive Impairment (MCI): A Two-Year Prospective Study

Antioxidants ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1839
Author(s):  
Chieh-Hsin Lin ◽  
Hsien-Yuan Lane
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Cognitive Function ◽  
Prospective Study ◽  
Cognitive Decline ◽  
Cognitive Change ◽  
Disease Assessment ◽  
Healthy Individuals

Glutathione (GSH) is a major endogenous antioxidant. Several studies have shown GSH redox imbalance and altered GSH levels in Alzheimer’s disease (AD) patients. Early detection is crucial for the outcome of AD. However, whether GSH can serve as a biomarker during the very early-phase of AD, such as mild cognitive impairment (MCI), remains unknown. The current prospective study aimed to examine the longitudinal change in plasma GSH concentration and its influence on cognitive decline in MCI. Overall, 49 patients with MCI and 16 healthy individuals were recruited. Plasma GSH levels and cognitive function, measured by the Mini-Mental Status Examination (MMSE) and Alzheimer’s disease assessment scale-cognitive subscale (ADAS-cog), were monitored every 6 months. We employed multiple regressions to examine the role of GSH level in cognitive decline in the 2 years period. The MCI patients showed significant decline in plasma GSH levels and cognitive function from baseline to endpoint (month 24). In comparison, the healthy individuals’ GSH concentration and cognitive function did not change significantly. Further, both GSH level at baseline and GSH level change from baseline to endpoint significantly influenced cognitive decline among the MCI patients. To our knowledge, this is the first study to demonstrate that both plasma GSH levels and cognitive function declined 2 years later among the MCI patients in a prospective manner. If replicated by future studies, blood GSH concentration may be regarded as a biomarker for monitoring cognitive change in MCI.

scholarly journals A SERUM PROTEIN SIGNATURE OF APOE GENOTYPES IN CENTENARIANS

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S621-S622
Author(s):  
Stefano Monti ◽  
Stefano Monti ◽  
Paola Sebastiani ◽  
Anastasia Gurinovich ◽  
Toshiko Tanaka ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Function ◽  
Late Onset ◽  
Expression Profiles ◽  
Apoe Genotype ◽  
Cognitive Change ◽  
Serum Proteomics ◽  
Apoe Genotypes ◽  
Protein Signature

Abstract The discovery of treatments to prevent or delay Alzheimer’s disease is a priority. The gene APOE is associated with cognitive change and late onset Alzheimer’s disease, and epidemiological studies have shown that the e_2 allele of APOE has a neuroprotective effect, and it is associated with increased longevity. We correlated APOE genotype data of 222 New England Centenarian Study participants, including 79 centenarians, 84 centenarian offspring and 55 carriers of APOE e_2, with aptamer-based serum proteomics (SomaLogic technology) of 4783 human proteins corresponding to 4137 genes. We discovered a signature of 16 proteins that associated with different APOE genotypes, and replicated the signature in 3 independent studies. We show that the protein signature tracks with gene expression profiles in brains of late onset Alzheimer’s disease vs. healthy controls. Finally, we show that seven of these proteins correlate with cognitive function changes. Therefore, targeting APOE e_2 molecularly may preserve cognitive function.

Abstract WMP115: The Metabolic Syndrome Components and Cognitive Decline: The Atherosclerosis Risk in Communities (ARIC) Study

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Jennifer L Dearborn ◽  
David Knopman ◽  
Richey Sharrett ◽  
Andrea L Schneider ◽  
Clifford Jack ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Cognitive Function ◽  
Cognitive Decline ◽  
Sex Education ◽  
Later Life ◽  
Cognitive Change ◽  
Word Recall ◽  
Digit Symbol Substitution Test ◽  
The Metabolic Syndrome ◽  
Aric Study

Background: Midlife obesity is associated with dementia in later life, but how the metabolic syndrome (MetS) relates to cognitive change is less understood. We hypothesized that MetS would be more predictive of 6-year cognitive decline than its individual components in a large biethnic cohort (the ARIC study) and that combinations of risk factors would further increase likelihood of change. Methods: The MetS was defined in 1987-89 on 10,687 participants with two cognitive assessments at two time points. In subjects aged 44 to 66, obesity measures included body mass index (BMI) and waist-to-hip ratio (WTHR). The main outcome measure was change in 1990-92 to 96-99 of three cognitive tests: Delayed Word Recall (DWR), Digit Symbol Substitution Test (DSST), and Word Fluency Test (WFT). Linear and logistic regressions were all adjusted for age, combined race-center, sex, education, smoking, drinking, coronary artery disease and prior stroke. Change was measured as the difference divided by the number of years between visits. Results: At baseline, the prevalence of MetS was 22% (mean age 54 years, 27% black, 55% female, and 28% BMI>30 kg/m2). Subjects with MetS performed in the lowest test quintile (adjusted ORs: DWR 1.3 95% CI 1.1-1.4) in 1996-99, and much of this effect size was explained by an elevated WTHR (DWR OR 1.3 CI 1.1-1.5) and diabetes (DWR OR 1.4 CI 1.2-1.7). MetS was not associated with annual cognitive change, and diabetes was the only significant component associated with change (adjusted beta: DWR 0.03 p=.01, DSST 0.2 p<.001, WFT 0.09 p=.01). Conclusion: MetS at ages 44 to 66 was associated with worse cognitive function at follow-up, but not with annual cognitive decline over several years. Elevated WTHR and diabetes explained most of the association of MetS with cognitive function measures, and diabetes with cognitive decline. Until we have a definition of the MetS more based on pathophysiology, the components of the MetS should be the focus of analysis in future studies.

scholarly journals 322 - Heterogeneity in dynamic change of cognitive function among Chinese elderly: A growth mixture model

2020 ◽  
Vol 32 (S1) ◽  
pp. 80-80
Author(s):  
Peiyuan Qiu ◽  
Weihong Kuang ◽  
Yan Cai ◽  
Yang Wan
Keyword(s):  
Risk Factors ◽  
Cognitive Function ◽  
Cognitive Decline ◽  
Mixture Model ◽  
Dynamic Change ◽  
Cognitive Change ◽  
Stable Group ◽  
Growth Mixture Model ◽  
Growth Mixture ◽  
Fresh Vegetables

Objectives:Our aim is to use the growth mixture model (GMM) to distinguish different trajectories of cognitive change in Chinese geriatric population and identify risk factors for cognitive decline in each subpopulation.Methods:We obtained data from the Chinese Longitudinal Health Longevity Survey, using the Chinese Mini-Mental State Examination (C-MMSE) as a proxy for cognitive function. We applied the GMM to identify heterogeneous subpopulations and potential risk factors.Results:Our sample included 2850 older adults, 1387 (48.7%) male and 1463 (51.3%) female with age range of 62 to 108 (average of 72.3). Using GMM and best fit statistics, we identified two distinct subgroups in respect to their longitudinal cognitive function: cognitively stable (91.4%) group with 0.42 C-MMSE points decline per 3 years, and cognitively declining (8.6%) group with 4.76 C-MMSE points decline per 3 years. Of note, vision impairment and hearing impairment had the highest associations with cognitive decline, with stronger association found in the cognitively declining group than the cognitively stable group. Cognitive activities were protective in both groups. Diabetes was associated with cognitive decline in cognitive declining group. Physical activities, social activities and intake of fresh vegetables, fruits, and fish products were protective in cognitive stable group.Conclusions:Using GMM, we identified heterogeneity in trajectories of cognitive change in Chinese elders. Moreover, we found risk factors specific to each subgroup, which should be considered in future studies.

Age is no kinder to the better educated: absence of an association investigated using latent growth techniques in a community sample

2001 ◽  
Vol 31 (1) ◽  
pp. 15-28 ◽  
Author(s):  
H. CHRISTENSEN ◽  
S. M. HOFER ◽  
A. J. MACKINNON ◽  
A. E. KORTEN ◽  
A. F. JORM ◽  
...  
Keyword(s):  
Cognitive Decline ◽  
Growth Models ◽  
Cognitive Change ◽  
Interaction Effects ◽  
Rate Of Change ◽  
Latent Growth ◽  
Latent Growth Models ◽  
Highly Educated ◽  
Regression Techniques ◽  
Rate Of Decline

Background. Higher education has been posited to protect against cognitive decline, either because the rate of decline is slower in the more highly educated or the start of decline is delayed. Latent growth models provide improved methodology to examine this issue.Methods. The sample consisted of 887 participants aged 70–93 years in 1991 and followed up in 1994 and 1998. Latent growth models and standard regression techniques were used to examine the rate of cognitive decline in four cognitive measures while controlling for health status and sex. A delayed start model was examined by incorporating interaction effects in a regression model.Results. Neither the latent growth models nor the regression techniques revealed a slower rate of decline for the more highly educated. The proportion of the highly educated showing no change was no larger than the proportion of the less well educated. There were no significant age by education interaction effects, no chronologically later accelerations in the rate of change as a function of education, and no differences in rate of decline between the first measurement interval and the second.Conclusions. Education may not protect against cognitive decline although it is associated with long-term individual differences in level of functioning. The discrepancy between our study and others may be attributable to attrition effects, follow-up length, sample age, scaling artefacts and negative publication bias. Most importantly, practice effects may favour the better educated and hence account for the supposed protective effect in many longitudinal studies of cognitive change.

scholarly journals Prediction of Cognitive Decline Using Heart Rate Fragmentation Analysis: The Multi-Ethnic Study of Atherosclerosis

2021 ◽  
Vol 13 ◽  
Author(s):  
Madalena D. Costa ◽  
Susan Redline ◽  
Timothy M. Hughes ◽  
Susan R. Heckbert ◽  
Ary L. Goldberger
Keyword(s):  
Risk Factors ◽  
Heart Rate ◽  
Cognitive Function ◽  
Cognitive Decline ◽  
Cognitive Performance ◽  
Digit Span ◽  
Cognitive Status ◽  
Therapeutic Interventions ◽  
Ethnic Study ◽  
Non Invasive

Background: Heart rate fragmentation (HRF), a new non-invasive metric quantifying cardiac neuroautonomic function, is associated with increasing age and cardiovascular disease. Since these are risk factors for cognitive decline and dementia, in the Multi-Ethnic Study of Atherosclerosis (MESA), we investigated whether disrupted cardiac neuroautonomic function, evidenced by increased HRF, would be associated with worse cognitive function assessed concurrently and at a later examination, and with greater cognitive decline.Methods: HRF was derived from the ECG channel of the polysomnographic recordings obtained in an ancillary study (n = 1,897) conducted in conjunction with MESA exam 5 (2010–2012). Cognitive function was assessed at exam 5 and 6.4 ± 0.5 years later at exam 6 (2016–2018) with tests of global cognitive performance (the Cognitive Abilities Screening Instrument, CASI), processing speed (Digit Symbol Coding, DSC) and working memory (Digit Span). Multivariable regression models were used to quantify the associations between HRF indices and cognitive scores.Results: The participants’ mean age was 68 ± 9 years (54% female). Higher HRF at baseline was independently associated with lower cognitive scores at both exams 5 and 6. Specifically, in cross-sectional analyses, a one-standard deviation (SD) (13.7%) increase in HRF was associated with a 0.51 (95% CI: 0.17–0.86) points reduction in CASI and a 1.12 (0.34–1.90) points reduction in DSC. Quantitatively similar effects were obtained in longitudinal analyses. A one-SD increase in HRF was associated with a 0.44 (0.03–0.86) and a 1.04 (0.28–1.81) points reduction in CASI and DSC from exams 5 to 6, respectively. HRF added predictive value to the Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE-APOE-ε4) risk score and to models adjusted for serum concentration of NT-proBNP, an analyte associated with cognitive impairment and dementia.Conclusion: Increased HRF assessed during sleep was independently associated with diminished cognitive performance (concurrent and future) and with greater cognitive decline. These findings lend support to the links between cardiac neuroautonomic regulation and cognitive function. As a non-invasive, repeatable and inexpensive probe, HRF technology may be useful in monitoring cognitive status, predicting risk of dementia and assessing therapeutic interventions.

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