Genetic modifiers of cognitive maintenance among older adults.

ObjectiveIdentify genetic factors associated with cognitive maintenance in late life and assess their association with gray matter (GM) volume in brain networks affected in aging.MethodsWe conducted a genome-wide association study of ∼2.4 M markers to identify modifiers of cognitive trajectories in Caucasian participants (N = 7,328) from two population-based cohorts of non-demented elderly. Standardized measures of global cognitive function (z-scores) over 10 and 6 years were calculated among participants and mixed model regression was used to determine subject-specific cognitive slopes. "Cognitive maintenance" was defined as a change in slope of ≥ 0 and was compared with all cognitive decliners (slope < 0). In an independent cohort of cognitively normal older Caucasians adults (N = 122), top association findings were then used to create genetic scores to assess whether carrying more cognitive maintenance alleles was associated with greater GM volume in specific brain networks using voxel-based morphometry.ResultsThe most significant association was on chromosome 11 (rs7109806, P = 7.8 × 10(-8)) near RIC3. RIC3 modulates activity of α7 nicotinic acetylcholine receptors, which have been implicated in synaptic plasticity and beta-amyloid binding. In the neuroimaging cohort, carrying more cognitive maintenance alleles was associated with greater volume in the right executive control network (RECN; PFWE  = 0.01).ConclusionsThese findings suggest that there may be genetic loci that promote healthy cognitive aging and that they may do so by conferring robustness to GM in the RECN. Future work is required to validate top candidate genes such as RIC3 for involvement in cognitive maintenance

Validation of the Kidney Disease Quality of Life (KDQOL) Cognitive Function subscale

Validation of the Kidney Disease Quality of Life (KDQOL) Cognitive Function subscale.BackgroundFormal cognitive function testing is cumbersome, and no self-administered instruments for estimating cognitive function in persons with chronic kidney disease (CKD) and end-stage renal disease (ESRD) have been validated. The goal of this study was to determine the validity of the Kidney Disease Quality of Life Cognitive Function scale (KDQOL-CF) for the assessment of cognitive impairment in persons with kidney disease.MethodsWe administered the KDQOL-CF to 157 subjects, 79 with ESRD and 78 with CKD participating in a cross-sectional study of cognitive function. Scores on the Modified Mini-Mental State Exam (3MS) were considered the gold standard measure of global cognitive function. Performance characteristics of the KDQOL-CF were assessed using correlation coefficients, Bland-Altman plots, and receiver operating characteristic curves.ResultsMedian scores on the KDQOL-CF were 73 (interquartile range 60–87) for subjects with ESRD and 87 (interquartile range 73–100) for subjects with CKD (P < 0.0001). Scores on the KDQOL-CF were directly correlated with scores on the 3MS (r = 0.31, P = 0.0001). Defining global cognitive impairment as a 3MS score <80, a cut-point of 60 on the KDQOL-CF accurately classified 76% of subjects, with 52% sensitivity and 81% specificity. On multivariable analysis, cerebral and peripheral vascular disease, benzodiazepine use, and higher serum phosphorus concentrations were associated with lower KDQOL-CF scores, while beta blocker use, education, and higher serum albumin concentrations were associated with higher KDQOL-CF scores.ConclusionThe KDQOL-CF is a valid instrument for estimating cognitive function in patients with CKD and ESRD. KDQOL-CF screening followed by 3MS testing in selected individuals may prove to be an effective and efficient strategy for identifying cognitive impairment in patients with kidney disease

Youthful Processing Speed in Older Adults: Genetic, Biological, and Behavioral Predictors of Cognitive Processing Speed Trajectories in Aging.

Objective: To examine the impact of genetic, inflammatory, cardiovascular, lifestyle, and neuroanatomical factors on cognitive processing speed (CPS) change over time in functionally intact older adults. Methods: This observational study conducted over two time points, included 120 community dwelling cognitively normal older adults between the ages of 60 and 80 from the University of California San Francisco Memory and Aging Center. Participants were followed with composite measures of CPS, calculated based on norms for 20-30 year-olds. Variables of interest were AD risk genes (APOE, CR1), markers of inflammation (interleukin 6) and cardiovascular health (BMI, LDL, HDL, mean arterial pressure, fasting insulin), self-reported physical activity, and corpus callosum (CC) volumes. The sample was divided into three groups: 17 "resilient-agers" with fast and stable processing speed; 56 "average-agers" with average and stable processing speed; and 47 "sub-agers" with average baseline speed who were slower at follow-up. Results: Resilient-agers had larger baseline CC volumes than sub-agers (p &lt; 0.05). Resilient-agers displayed lower levels of interleukin-6 (IL-6) and insulin (ps &lt; 0.05) than sub-agers, and reported more physical activity than both average- and sub-agers (ps &lt; 0.01). In a multinomial logistic regression, physical activity and IL-6 predicted average- and sub-ager groups. Resilient-agers displayed a higher frequency of APOE e4 and CR1 AA/AG alleles. Conclusion: Robust and stable CPS is associated with larger baseline CC volumes, lower levels of inflammation and insulin, and greater self-reported physical activity. These findings highlight the relevance of neuroanatomical, biological, and lifestyle factors in the identification and prediction of heterogeneous cognitive aging change over time

Traumatic brain injury in later life increases risk for Parkinson disease

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111787/1/ana24396.pd

American Geriatrics Society and National Institute on Aging Bench-to-Bedside conference: sensory impairment and cognitive decline in older adults

This article summarizes the presentations and recommendations of the tenth annual American Geriatrics Society and National Institute on Aging Bench‐to‐Bedside research conference, “Sensory Impairment and Cognitive Decline,” on October 2–3, 2017, in Bethesda, Maryland. The risk of impairment in hearing, vision, and other senses increases with age, and almost 15% of individuals aged 70 and older have dementia. As the number of older adults increases, sensory and cognitive impairments will affect a growing proportion of the population. To limit its scope, this conference focused on sensory impairments affecting vision and hearing. Comorbid vision, hearing, and cognitive impairments in older adults are more common than would be expected by chance alone, suggesting that some common mechanisms might affect these neurological systems. This workshop explored the mechanisms and consequences of comorbid vision, hearing, and cognitive impairment in older adults; effects of sensory loss on the aging brain; and bench‐to‐bedside innovations and research opportunities. Presenters and participants identified many research gaps and questions; the top priorities fell into 3 themes: mechanisms, measurement, and interventions. The workshop delineated specific research questions that provide opportunities to improve outcomes in this growing population.Funding was provided by National Institutes of Health (NIH) Grant U13 AG054139-01. Dr. Whitson's efforts and contributions were supported by R01AG043438, R24AG045050, UH2AG056925, and 5P30AG028716. Dr. Lin's effort and contributions were also supported by R01AG055426, R01HL096812, and R33DC015062. (U13 AG054139-01 - National Institutes of Health (NIH); R01AG043438; R24AG045050; UH2AG056925; 5P30AG028716; R01AG055426; R01HL096812; R33DC015062)Accepted manuscrip

Systematic Multi-Domain Alzheimer's Risk Reduction Trial (SMARRT): Study Protocol.

This article describes the protocol for the Systematic Multi-domain Alzheimer's Risk Reduction Trial (SMARRT), a single-blind randomized pilot trial to test a personalized, pragmatic, multi-domain Alzheimer's disease (AD) risk reduction intervention in a US integrated healthcare delivery system. Study participants will be 200 higher-risk older adults (age 70-89 years with subjective cognitive complaints, low normal performance on cognitive screen, and ≥ two modifiable risk factors targeted by our intervention) who will be recruited from selected primary care clinics of Kaiser Permanente Washington, oversampling people with non-white race or Hispanic ethnicity. Study participants will be randomly assigned to a two-year Alzheimer's risk reduction intervention (SMARRT) or a Health Education (HE) control. Randomization will be stratified by clinic, race/ethnicity (non-Hispanic white versus non-white or Hispanic), and age (70-79, 80-89). Participants randomized to the SMARRT group will work with a behavioral coach and nurse to develop a personalized plan related to their risk factors (poorly controlled hypertension, diabetes with evidence of hyper or hypoglycemia, depressive symptoms, poor sleep quality, contraindicated medications, physical inactivity, low cognitive stimulation, social isolation, poor diet, smoking). Participants in the HE control group will be mailed general health education information about these risk factors for AD. The primary outcome is two-year cognitive change on a cognitive test composite score. Secondary outcomes include: 1) improvement in targeted risk factors, 2) individual cognitive domain composite scores, 3) physical performance, 4) functional ability, 5) quality of life, and 6) incidence of mild cognitive impairment, AD, and dementia. Primary and secondary outcomes will be assessed in both groups at baseline and 6, 12, 18, and 24 months

Lipid Peroxidation and Depressed Mood in Community-Dwelling Older Men and Women

It has been hypothesized that cellular damage caused by oxidative stress is associated with late-life depression but\ud epidemiological evidence is limited. In the present study we evaluated the association between urinary 8-iso-prostaglandin\ud F2a (8-iso-PGF2a), a biomarker of lipid peroxidation, and depressed mood in a large sample of community-dwelling older\ud adults. Participants were selected from the Health, Aging and Body Composition study, a community-based longitudinal\ud study of older persons (aged 70–79 years). The present analyses was based on a subsample of 1027 men and 948 women\ud free of mobility disability. Urinary concentration of 8-iso-PGF2a was measured by radioimmunoassay methods and adjusted\ud for urinary creatinine. Depressed mood was defined as a score greater than 5 on the 15-item Geriatric Depression Scale and/\ud or use of antidepressant medications. Depressed mood was present in 3.0% of men and 5.5% of women. Depressed men\ud presented higher urinary concentrations of 8-iso-PGF2a than non-depressed men even after adjustment for multiple\ud sociodemographic, lifestyle and health factors (p=0.03, Cohen’s d = 0.30). This association was not present in women\ud (depressed status-by-sex interaction p = 0.04). Our study showed that oxidative damage may be linked to depression in\ud older men from a large sample of the general population. Further studies are needed to explore whether the modulation of\ud oxidative stress may break down the link between late-life depression and its deleterious health consequences

Risk factors for incident dementia among older Cubans

Introduction: Little is known about risk factors of dementia in Latin American countries. We aimed to identify socio-demographic, health and lifestyle risk factors of incident dementia in Cuban older adults. Methods: Data were from 1,846 participants in the Cuban cohort of the 10/66 Dementia Research Group. Participants completed questionnaires, health examinations, and cognitive tests at baseline (2003-2006) and 4.5 years later (2007-2010). Associations between risk factors (baseline) and incident dementia (follow-up) were examined using logistic regression. Results: Just over 9% of participants developed dementia. Overall, older age and low physical activity were associated with incident dementia. In those 65-74 years of age, depression, stroke and low physical activity were associated with incident dementia. In those ≥75 years of age, low physical activity, never eating fish, and smoking were associated with incident dementia. Conclusions: Modifiable lifestyle factors play an important role in developing dementia in Cuban older adults. This knowledge opens up opportunities for preventive strategies

Interleukin-6, age, and corpus callosum integrity.

The contribution of inflammation to deleterious aging outcomes is increasingly recognized; however, little is known about the complex relationship between interleukin-6 (IL-6) and brain structure, or how this association might change with increasing age. We examined the association between IL-6, white matter integrity, and cognition in 151 community dwelling older adults, and tested whether age moderated these associations. Blood levels of IL-6 and vascular risk (e.g., homocysteine), as well as health history information, were collected. Processing speed assessments were administered to assess cognitive functioning, and we employed tract-based spatial statistics to examine whole brain white matter and regions of interest. Given the association between inflammation, vascular risk, and corpus callosum (CC) integrity, fractional anisotropy (FA) of the genu, body, and splenium represented our primary dependent variables. Whole brain analysis revealed an inverse association between IL-6 and CC fractional anisotropy. Subsequent ROI linear regression and ridge regression analyses indicated that the magnitude of this effect increased with age; thus, older individuals with higher IL-6 levels displayed lower white matter integrity. Finally, higher IL-6 levels were related to worse processing speed; this association was moderated by age, and was not fully accounted for by CC volume. This study highlights that at older ages, the association between higher IL-6 levels and lower white matter integrity is more pronounced; furthermore, it underscores the important, albeit burgeoning role of inflammatory processes in cognitive aging trajectories

Sex Differences in the Association Between Cumulative Use of Cannabis and Cognitive Function in Middle Age: The Coronary Artery Risk Development in Young Adults Study.

Background: Cannabis use may impair cognitive function (CF) differently in men and women, due to sex-specific differences in neurobiological mechanisms and environmental risk factors. Objective: Assess sex differences in the association between cumulative exposure to cannabis and cognitive performance in middle age. Methods: We studied participants from the Coronary Artery Risk Development in Young Adults (CARDIA) Study, including Black and White men and women 18-30 years old at baseline followed over 30 years. Our cross-sectional analysis of CF scores at year 30 was stratified by sex. We computed categories of cumulative exposure in "cannabis-years" (1 cannabis-year=365 days of use) from self-reported use every 2 to 5 years over 30 years. At years 25 and 30, we assessed CF with the Rey Auditory Verbal Learning Test (verbal memory), the Digit Symbol Substitution Test (processing speed), and the Stroop Interference Test (executive function). At year 30, additional measures included Category and Letter Fluency Test (verbal ability) and the Montreal Cognitive Assessment (global cognition). We computed standardized scores for each cognitive test and applied multivariable adjusted linear regression models for self-reported cumulative cannabis use, excluding participants who used cannabis within 24 h. In a secondary analysis, we examined the association between changes in current cannabis use and changes in CF between years 25 and 30. Results: By year 30, 1,352 men and 1,793 women had measures of CF; 87% (N=1,171) men and 84% (N=1,502) women reported ever cannabis use. Men had a mean cumulative use of 2.57 cannabis-years and women 1.29 cannabis-years. Self-reported cumulative cannabis use was associated with worse verbal memory in men (e.g., -0.49 standardized units [SU] for ≥5 cannabis-years of exposure; 95% CI=-0.76 to -0.23), but not in women (SU=0.02; 95% CI=-0.26 to 0.29). Other measures of CF were not associated with cannabis. Changes in current cannabis use between years 25 and 30 were not associated with CF in men or women. Conclusions: Self-reported cumulative cannabis exposure was associated with worse verbal memory in men but not in women. Researchers should consider stratified analyses by sex when testing the association between cannabis and cognition