Nondemented Adults Research Articles

Longitudinal trajectories of Alzheimer\u2019s ATN biomarkers in elderly persons without dementia

BackgroundModels of Alzheimer’s disease (AD) pathophysiology posit that amyloidosis [A] precedes and accelerates tau pathology [T] that leads to neurodegeneration [N]. Besides this A-T-N sequence, other biomarker sequences are possible. This current work investigates and compares the longitudinal trajectories of Alzheimer’s ATN biomarker profiles in non-demented elderly adults from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort.MethodsBased on the ATN classification system, 262 individuals were identified before dementia diagnosis and accompanied by baseline and follow-up data of ATN biomarkers (CSF Aβ42, p-tau, and FDG-PET). We recorded the conversion processes in ATN biomarkers during follow-up, then analyzed the possible longitudinal trajectories and estimated the conversion rate and temporal evolution of biomarker changes. To evaluate how biomarkers changed over time, we used linear mixed-effects models.ResultsDuring a 6–120-month follow-up period, there were four patterns of longitudinal changes in Alzheimer’s ATN biomarker profiles, from all negative to positive through the course of the disease. The most common pattern is that A pathology biomarker first emerges. As well as the classical A-T-N sequence, other “A-first,” “T-first,” and “N-first” biomarker pathways were found. The N-A-T sequence had the fastest rate of pathological progression (mean 65.00 months), followed by A-T-N (mean 67.07 months), T-A-N (mean 68.85 months), and A-N-T sequences (mean 98.14 months).ConclusionsOur current work presents a comprehensive analysis of longitudinal trajectories of Alzheimer’s ATN biomarkers in non-demented elderly adults. Stratifying disease into subtypes depending on the temporal evolution of biomarkers will benefit the early recognition and treatment.

Cognitive Correlates of Digital Clock Drawing Metrics in Older Adults with and without Mild Cognitive Impairment.

A digital version of the clock drawing test (dCDT) provides new latency and graphomotor behavioral measurements. These variables have yet to be validated with external neuropsychological domains in non-demented adults. The current investigation reports on cognitive constructs associated with selected dCDT latency and graphomotor variables and compares performances between individuals with mild cognitive impairment (MCI) and non-MCI peers. 202 non-demented older adults (age 68.79 ± 6.18, 46% female, education years 16.02 ± 2.70) completed the dCDT and a comprehensive neuropsychological protocol. dCDT variables of interest included: total completion time (TCT), pre-first hand latency (PFHL), post-clock face latency (PCFL), and clock face area (CFA). We also explored variables of percent time drawing (i.e., 'ink time') versus percent time not drawing (i.e., 'think time'). Neuropsychological domains of interest included processing speed, working memory, language, and declarative memory. Adjusting for age and premorbid cognitive reserve metrics, command TCT positively correlated with multiple cognitive domains; PFHL and PCFL negatively associated with worse performance on working memory and processing speed tests. For Copy, TCT, PCFL, and PFHL negatively correlated with processing speed, and CFA negatively correlated with language. Between-group analyses show MCI participants generated slower command TCT, produced smaller CFA, and required more command 'think' (% Think) than 'ink' (% Ink) time. Command dCDT variables of interest were primarily processing speed and working memory dependent. MCI participants showed dCDT differences relative to non-MCI peers, suggesting the dCDT may assist with classification. Results document cognitive construct validation to digital metrics of clock drawing.

Normative Data of the Phonemic Fluency Test in Korean Middle-Aged and Elderly Population

Objective：The available normative data for the phonemic fluency test in Korean older adults have concerns for its utility. The aim of the currently study is to provide the normative data that overcome the issues of the previous norms. Methods：Total of 443 middle- and old-aged non-demented adults participated in this study. All participants underwent comprehensive assessments conducted by trained psychiatrists and psychologists. Diagnosis was made based on formal guidelines prior to administering the phonemic fluency test. Results：The norms on two age groups (50-59 and 60-90 years) with different strata of the education levels for the age groups are provided. Conclusion：The goal of the current study, which was to overcome the shortcomings of the previously published normative data and establish an updated reference for the Korean version of the phonemic fluency test, is achieved.

Association of sleep with cognition and beta amyloid accumulation in adults with Down syndrome

Adults with Down syndrome have an increased risk for both disordered sleep and Alzheimer’s disease (AD). In the general population, disrupted sleep has been linked to beta amyloid accumulation, an early pathophysiologic feature of AD. In this study, the association among sleep, beta amyloid, and measures of AD-related cognitive decline was examined in 47 non-demented adults with Down syndrome (aged 26–56 years). Sleep was measured using actigraphy over 7 nights. Pittsburgh Compound B positron emission tomography was used to assess global and striatal beta amyloid burden. Participants had the following clinical AD status: 7 (15%) mild cognitive impairment and 40 (85%) cognitively unaffected. Average length of night-time awakenings was significantly positively associated with striatal beta amyloid and decreased cognitive performance in executive functioning and motor planning and coordination. Findings suggest that disrupted sleep is associated with beta amyloid accumulation and cognitive features of preclinical AD in Down syndrome. Early identification and treatment of sleep problems could be a lifestyle intervention that may delay beta amyloid accumulation and cognitive decline in this AD vulnerable group.

Genetic Association Between Alzheimer's Disease Risk Variant of the PICALM Gene and EEG Functional Connectivity in Non-demented Adults.

Genome wide association studies (GWAS) have identified and validated the association of the PICALM genotype with Alzheimer’s disease (AD). The PICALM rs3851179 A allele is thought to have a protective effect, whereas the G allele appears to confer risk for AD. The influence of the PICALM genotype on brain functional connectivity in non-demented subjects remains largely unknown. We examined the association of the PICALM rs3851179 genotype with the characteristics of lagged linear connectivity (LLC) of resting EEG sources in 104 non-demented adults younger than 60 years of age. The EEG analysis was performed using exact low-resolution brain electromagnetic tomography (eLORETA) freeware (Pascual-Marqui et al., 2011). We found that the carriers of the A PICALM allele (PICALM AA and AG genotypes) had higher widespread interhemispheric LLC of alpha sources compared to the carriers of the GG PICALM allele. An exploratory correlation analysis showed a moderate positive association between the alpha LLC interhemispheric characteristics and the corpus callosum size and between the alpha interhemispheric LLC characteristics and the Luria word memory scores. These results suggest that the PICALM rs3851179 A allele provides protection against cognitive decline by facilitating neurophysiological reserve capacities in non-demented adults. In contrast, lower functional connectivity in carriers of the AD risk variant, PICALM GG, suggests early functional alterations in alpha rhythm networks.

Association of Frailty with recovery from disability among community-dwelling Chinese older adults: China health and retirement longitudinal study

BackgroundsLittle is known about the role of frailty in the recovery process of disability among older adults. We examined the association between frailty and recovery from activities of daily living (ADL) and instrumental ADL (IADL) disability among community-dwelling Chinese older adults.MethodsData were from the China Health and Retirement Longitudinal Study. Three waves were used. Participants ≥60 years, had frailty assessment at baseline, and had incident disability in ADL or IADL in 2013, and had disability assessment in 2015 were included. Recovery from ADL and IADL disability were used as outcome measure. Multivariable logistic regression was used to evaluate the potential association between frailty and recovery from ADL or IADL.ResultsWe included 516 and 598 participants in the ADL and IADL analysis, respectively. In total, 237 participants recovered from ADL disability and 293 recovered from IADL disability. Nearly half of the non-frail persons recovered from ADL disability, while less than one-quarter of the frail persons had recovery. Over half of the non-frail persons had IADL disability recovery, while only 30% of the frail recovered. After adjustment, the odds of recovery from ADL disability were 59% (95% confidence interval [CI]: 1, 83%) lower among frail participants than those who were non-frail; the odds of recovery from IADL disability were 52% lower among frail persons than those who were non-frail and the association did not reach statistical significance.ConclusionsFrailty is an independent predictor of poor recovery from disability among nondisabled community-dwelling older adults in China.

COGNITIVE TEST DISPERSION AND FUNCTIONAL CONNECTIVITY IN OLDER ADULTS WITH MAJOR DEPRESSION

Introduction Performance variability across a battery of cognitive tests, otherwise known as dispersion, has been shown to be predictive of an increased risk of developing Mild Cognitive Impairment (MCI) and Alzheimer's disease. We previously found that test dispersion in older adults with major depression was: 1) correlated with white matter disease on structural MRI and 2) predictive of worsening on memory test performance one year later (even when controlling for baseline memory test performance and other relevant clinical and demographic factors). There is little evidence regarding fMRI and dispersion and the underlying functional connectivity impact that increased dispersion may have on neural networks. The goal of the current study was to explore the relationship between cognitive dispersion and resting-state activity measured by amplitude of low-frequency fluctuation (ALFF) and functional connectivity in non-demented older adults diagnosed with major depression. We hypothesized that dispersion would be correlated with resting-state activity as well as functional connectivity in neural networks related to executive functioning and memory. Methods Subjects included 61 older adults with major depression (MD) who had participated in the NBOLD study at UConn Health. Inclusion criteria included age 60+ and a formal diagnosis of major depression. Those with dementia or other significant neuropsychiatric disorders were excluded from the study. Dispersion was defined as the spread of scores on a comprehensive neuropsychological battery, calculated as the coefficient of variation, or standard deviation of z-scores divided by the group mean z-scores. 7-min resting state fMRI data was acquired from 3T Siemens scanner. DPABI software was used to conduct preprocessing and ALFF calculation. Significant clusters that showed ALFF correlation between ALFF and dispersion (p Results Subject demographics were as follows; age (Mean=71.8yrs, SD=±7.3yrs), 27.9% male, MADRS (Mean=18.2, SD=±6.2). ALFF in the posterior cingulate cortex (PCC) and left hippocampal cortex (LHC) were negatively correlated with dispersion while ALFF of the dorsolateral prefrontal cortex (dlPFC) was positively correlated with dispersion. Using these regions as ROIs, we found functional connectivity between the dlPFC seed and left inferior parietal cortex ((angular gyrus), peak -58, -56, 24; cluster size 110; p=.00196), the executive network, was positively correlated with cognitive dispersion. Conclusions Dispersion is negatively correlated with ALFF in brain areas related to memory (hippocampus and PCC), but positively related to ALFF in the dlPFC, a key region of executive functioning and attention. Functional connectivity of the executive network was also positively correlated with dispersion, suggesting possible deficits in resting activity of the memory system, and compensatory increase of resting activity and connectivity of the executive system in MD subjects with high dispersion. Future studies may continue to look at anatomical relationships with cognitive dispersion and performance on neuropsychological tests in those with MD, as well as further explore the impact that dispersion has on neural networks. This research was funded by: Data and research that was reported in this poster was supported by the National Institute of General Medical Sciences of the National Institutes of Health under linked Award Numbers RL5GM118969, TL4GM118971, and UL1GM118970; by NIMH grant R01 MH108578; and by the Leo and Anne Albert Charitable Trust. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Late-Life Physical and Cognitive Activities Independently Contribute to Brain and Cognitive Resilience.

Active lifestyles are related to better cognitive aging outcomes, yet the unique role of different types of activity are unknown. To examine the independent contributions of physical (PA) versus cognitive (CA) leisure activities to brain and cognitive aging. Independent samples of non-demented older adults from University of California, San Francisco Hillblom Aging Network (UCSF; n = 344 typically aging) and University of California, Davis Diversity cohort (UCD; n = 485 normal to MCI) completed: 1) self-reported engagement in current PA and CA (UCSF: Physical Activity Scale for the Elderly and Cognitive Activity Scale; UCD: Life Experiences Assessment Form); 2) neuropsychological batteries; and 3) neuroimaging total gray matter volume, white matter hyperintensities, and/or global fractional anisotropy. PA and CA were simultaneously entered into multivariable linear regression models, adjusting for demographic characteristics and functional impairment severity. Brain outcomes: In UCSF, only PA was positively associated with gray matter volume and attenuated the relationship between age and fractional anisotropy. In UCD, only CA was associated with less white matter hyperintensities and attenuated the relationship between age and gray matter volume. Cognitive outcomes: In both cohorts, greater CA, but not PA, related to better cognition, independent of age and brain structure. In UCSF, CA attenuated the relationship between fractional anisotropy and cognition. In UCD, PA attenuated the association between white matter hyperintensities and cognition. Although their specificity was not easily teased apart, both PA and CA are clearly related to better brain and cognitive resilience markers across cohorts with differing educational, racial, and disease statuses. PA and CA may independently contribute to converging neuroprotective pathways for brain and cognitive aging.

Walking while Talking in Older Adults with Chronic Kidney Disease.

Walking while talking is a dual cognitive-motor task that predicts frailty, falls, and cognitive decline in the general elderly population. Adults with CKD have gait abnormalities during usual walking. It is unknown whether they have greater gait abnormalities and cognitive-motor interference during walking while talking. Community-dwelling, nondisabled adults (n=330) ≥65 years of age underwent quantitative gait analysis, including walking while talking. Differences in walking-while-talking performance by CKD status were evaluated, and relative changes between walking-while-talking and walking alone performance were computed to quantify cognitive-motor interference (dual-task cost). Associations were tested using multivariable linear spline regression models, and independent gait domains were derived using factor analysis. CKD was defined as an eGFR<60 ml/min per 1.73 m2. CKD was present in 134 (41%) participants. Participants with CKD had slower gait speed along with various gait cycle abnormalities during walking while talking: among those with CKD, every 10-ml/min per 1.73 m2 lower eGFR was associated with 3.3-cm/s (95% confidence interval, 0.4 to 6.1) slower gait speed, 1.8-cm (95% confidence interval, 0.6 to 3.0) shorter step length, 1.1% (95% confidence interval, 0.6 to 1.7) less time in the swing phase, and 1.4% (95% confidence interval, 0.5 to 2.3) greater time in double support after multivariable adjustment. When comparing walking while talking with walking alone, every 10-ml/min per 1.73 m2 lower eGFR was associated with 1.8% (95% confidence interval, 0.5 to 3.2) greater decrease in time in the swing phase and 0.9% (95% confidence interval, 0.2 to 1.5) greater increase in time in the stance phase. Factor analysis identified three walking-while-talking domains and three dual-task cost domains: eGFR was associated specifically with the rhythm domain for both walking-while-talking and dual-task cost. Every 10-ml/min per 1.73 m2 lower eGFR was associated with a poorer performance of 0.2 SD (95% confidence interval, 0.1 to 0.3) for walking while talking and 0.2 SD (95% confidence interval, 0.03 to 0.3) for dual-task cost. During walking while talking, CKD is associated with gait abnormalities, possibly due to increased cognitive-motor interference.

Abstract MP26: Mediterranean Diet And Brain Magnetic Resonance Imaging Measures In Young And Older Adults

Introduction: Accumulative evidence has suggested that higher adherence to a healthy dietary pattern, such as Mediterranean diet (MeDi), is associated with preservation of brain structure and less cerebrovascular events. Little is known for these associations across lifespan. Hypothesis: We hypothesized that MeDi was associated with brain atrophy or small vessel pathology measured using magnetic resonance imaging (MRI) in a cohort of healthy adults aged 20-80. Methods: This cross-sectional study included 375 healthy, non-demented adults recruited from market mailing within a 50-mile radius of Columbia University Medical Center in New York City. The participants age ranged 20-80 years old (mean 55, SD=16); had on average 16 (SD=2.3) years of education; 210 (56%) were females; 67% were Whites, 20% African-Americans, and 13% others. MeDi score (range 0-9) was calculated based on food consumption information collected through food-frequency questionnaire. Total brain volume (TBV) and white matter hyperintensity (WMH) were derived from high-resolution structural MRI scans. We examined the association of MeDi with TBV (milliliter, adjusted for intracranial volume) and WMH (milliliter, log transformed) using regression models adjusted for age, gender, race, education, and total caloric intake. Stratified analyses were performed among young (20-45), mid-age (46-65), and older (65-80) adults. Results: In multivariable-adjusted linear regression models, one unit increase in MeDi score, indicating consumption of one more food meeting the desirable level, was associated with larger TBV (β=2.79, p=0.027) and of less WMH (β= -0.058, p=0.041), corresponding to roughly 1.8 years and 1.3 years of less aging (β=-1.54 for age on TBV and 0.044 for age on WMH), respectively. Furthermore, we found the association between MeDi and TBV was similar across age groups, while the association between MeDi and WMH was only significant in the young adults (b=-0.189, p=0.002). Conclusions: Higher MeDi adherence was associated with healthier brain, indicated by larger brain volumes and less white matter lesion burden. These findings suggest that following a healthy diet may help maintain brain health across life span. To our knowledge, this is the first study to examine the relation of MeDi adherence to brain measures in healthy adults of all ages. The novel findings, especially the finding of MeDi and WMH in young adults, are worth of further confirmation in larger and longitudinal studies.

Midlife Lifestyle Activities Moderate APOE ε4 Effect on in vivo Alzheimer's Disease Pathologies.

This study aimed to investigate whether the midlife cognitive activity and physical activity moderate the relationship between apolipoprotein Eε4 (APOE4) and in vivo Alzheimer’s disease (AD) pathologies. In total, 287 non-demented older adults (mean age 72 years) from the Korean Brain Aging Study for the Early diagnosis and prediction of Alzheimer’s disease cohort were included. Participants underwent a comprehensive clinical assessment including the evaluation for midlife CA and physical activity, [11C]-Pittsburgh-Compound-B-positron emission tomography (PET), [18F]-fluorodeoxyglucose PET, structural magnetic resonance imaging (MRI), and APOE genotyping. We used linear regression and regression-based mediated-moderation models for statistical analyses. Neither midlife cognitive activity nor physical activity moderated the effect of APOE4 on β-amyloid (Aβ) retention itself. Midlife cognitive activity significantly moderated the effect of APOE4 on hippocampal volume [B (SE) = − 627.580 (252.327), t = −2.488, p = 0.014]: APOE4 carriers had smaller hippocampal volume than non-carriers at relatively high cognitive activity state (p = 0.004), but not at relatively low cognitive activity condition (p = 0.937). Midlife physical activity significantly moderated the effect of Aβ retention, which was closely related to APOE4, on AD-signature region cerebral glucose metabolism [AD-CM; B (SE) = 0.004 (0.002), t = 2.030, p = 0.043]: higher Aβ accumulation was associated with lower AD-CM in relatively low physical activity condition (p < 0.001), whereas no such association was observed in relatively high physical activity state (p = 0.791). The findings suggest that high midlife cognitive activity may accelerate hippocampal atrophy induced by APOE4, whereas high midlife physical activity may delay AD-related cerebral hypometabolism by weakening the influence of APOE4-associated Aβ retention.

Examining the Moderating Role of a Mediterranean Diet in the Relationship Between Perceived Stress and Cognitive Function in Older Adults.

Perceived stress and adherence to a Mediterranean diet pattern have been identified as independent predictors of cognitive function in older adulthood; however, no studies to date have examined the interaction between perceived stress and diet adherence on cognitive health. This cross-sectional study investigated the synergistic effect of perceived stress and adherence to a Mediterranean diet pattern on cognitive function in 192 nondemented older adults aged 60-95 years. Participants completed a Food Frequency Questionnaire (FFQ) and the Perceived Stress Scale (PSS-10). Executive functioning was assessed using the Trail Making Test-Part B (TMT-B) and episodic memory was assessed using the immediate and delayed free recall subscales from the California Verbal Learning Test (CVLT-II). Moderation analyses revealed that higher perceived stress was associated with worse executive functioning at low levels of Mediterranean diet adherence (B = 1.75, SE = 0.67, p = .009), but not at moderate and high levels of Mediterranean diet adherence (ps > .05). Perceived stress was not associated with episodic memory, irrespective of Mediterranean diet adherence. Findings provide preliminary evidence that the association between higher perceived stress and poorer executive function may be dependent on diet intake. Additional research is needed to confirm these findings.

Effect of feedback and target size on eye gaze accuracy in an off-screen task

Purpose Eye gaze interfaces have been used by people with severe physical impairment to interact with various assistive technologies. If used to control robots, it would be beneficial if individuals could gaze directly at targets in the physical environment rather than have to switch their gaze between a screen with representations of robot commands and the physical environment to see the response of their selection. By using a homogeneous transformation technique, eye gaze coordinates can be mapped between the reference coordinate frame of eye tracker and the coordinate frame of objects in the physical environment. Feedback about where the eye tracker has determined the eye gaze is fixated is needed so users can select targets more accurately. Screen-based assistive technologies can use visual feedback, but in a physical environment, other forms of feedback need to be examined. Materials and methods In this study, an eye gaze system with different feedback conditions (i.e., visual, auditory, vibrotactile, and no-feedback) was tested when participants received visual feedback on a display (on-screen) and when looking directly at the physical environment (off-screen). Target selection tasks in both screen conditions were performed by ten non-disabled adults, three non-disabled children, and two adults and one child with cerebral palsy. Results Tasks performed with gaze fixation feedback modalities were accomplished faster and with higher success than tasks performed without feedback, and similar results were observed in both screen conditions. No significant difference was observed in performance across the feedback modalities, but participants had personal preferences. Conclusion The homogeneous transformation technique enabled the use of a stationary eye tracker to select target objects in the physical environment, and auditory and vibrotactile feedback enabled participants to be more accurate selecting targets than without it. Implications for Rehabilitation Being able to select target objects in the physical environment by eye gaze could make it easier for children with disabilities to control assistive robots, because in this way they do not have to change their focus between a computer screen with commands and the robot. Providing auditory or vibrotactile feedback when using an eye gaze system made it faster and easier to know if a target was being gazed upon. Being able to select targets in the environment using eye gaze could be beneficial for other assistive technology, too, such as destination selection for power wheelchairs.

Normative Values for the Short Physical Performance Battery (SPPB) and Their Association With Anthropometric Variables in Older Colombian Adults. The SABE Study, 2015.

Background: The short physical performance battery (SPPB) is a physical performance test of lower extremity function designed for non-disabled older adults. We aimed to establish reference values for community-dwelling Colombian adults aged 60 years or older in terms of (1) the total score; (2) the three subtest scores (walking speed, standing balance performance, and five times sit-to-stand test); and (3) the time to complete the five times sit-to-stand test, s and the walking speed test. Additionally, we sought to explore how much of the variance in the SPPB subtest scores could be explained by anthropometric variables (age, body mass, height, body mass index, and calf circumference).Methods: Participants were men and women aged 60 years or older who participated in the Health and Well-being and Aging Survey in Colombia, 2015. A sample of 4,211 participants (57.3% women) completed the SPPB test, and their anthropometric variables were evaluated. Age-specific percentiles were calculated using the LMS method (3rd, 10th, 25th, 50th, 75th, 90th, and 97th percentiles).Results: The mean SPPB total score for the entire sample was 8.73 (2.0) points. On average, the total SPPB score was 0.85 points greater in men than in women (p < 0.001). Significant sex differences were observed in all three age groups tested (60–69, 70–79, and 80+ years). In the full sample, our findings suggested that age, body mass, height, body mass index, and calf circumference are significant contributors to walking speed (p < 0.001) after controlling for confounding factors, including ethnicity, socioeconomic status, and urbanicity.Conclusions: Percentile values are of interest to identify target populations for primary prevention and to estimate the proportion of high or low values for SPPB measures in community-dwelling Colombians aged at least 60 years.

Waist Circumference and Domain-Specific Cognitive Function Among Non-Demented Japanese Older Adults Stratified by Sex: Results from the Takashima Cognition Study

While being obese in mid-life is associated with an increased risk of dementia and cognitive decline in late-life, being obese in late-life is shown to be associated with a lower risk of these outcomes in some studies. This phenomenon is known as the "obesity paradox", but the underlying reasons and potential sex difference have not been well understood. To investigate the association between cognition and waist circumference (WC), an alternative measure of body fat which can be measured easier than body mass index (BMI), among older adults in each generation of late-life for men and women separately. Three hundred thirty-five participants were used in the current study who were identified by random sampling of residents aged 65-74, 75-84, and 85 + years in Takashima County, Shiga Prefecture, Japan during 2005-2006. Associations between WC and domain-specific cognitive functions measured by 12 neuropsychological tests were examined using multivariable linear regression models with covariates: age, education, and hypertension. Larger WC was associated with better attention/working memory among 65-74-year old women and with better learning/acquisition among 65-74-year-old men, while larger WC was associated with worse learning/acquisition, memory, attention/working memory, and language/fluency among 75-84-year old men. We found age and sex differences in the association between WC and domain-specific cognitive functions. Among older old men (age 75-84), larger WC had negative effects on various domains including memory, attention, language, and executive functions, while we did not find any negative effects of larger WC on cognition among women in any age groups.

Differential annualized rates of hippocampal subfields atrophy in aging and future Alzheimer's clinical syndrome

Several studies have investigated the differential vulnerability of hippocampal subfields during aging and Alzheimer's disease (AD). Results were often contradictory, mainly because these works were based on concatenations of cross-sectional measures in cohorts with different ages or stages of AD, in the absence of a longitudinal design. Here, we investigated 327 participants from a population-based cohort of nondemented older adults with a 14-year clinical follow-up. MRI at baseline and 4 years later were assessed to measure the annualized rates of hippocampal subfields atrophy in each participant using an automatic segmentation pipeline with subsequent quality control. On the one hand, CA4 dentate gyrus was significantly more affected than the other subfields in the whole population (CA1-3: −0.68%/year; subiculum: −0.99%/year; and CA4-DG: −1.39%/year; p < 0.0001). On the other hand, the annualized rate of CA1-3 atrophy was associated with an increased risk of developing Alzheimer's clinical syndrome over time, independently of age, gender, educational level, and ApoE4 genotype (HR = 2.0; CI 95% 1.4–3.0). These results illustrate the natural history of hippocampal subfields atrophy during aging and AD by showing that the dentate gyrus is the most vulnerable subfield to the effects of aging while the cornu-ammonis is the primary target of AD pathophysiological processes, years before symptom onset.

Midlife Modifiable Risk Factors for Dementia: A Systematic Review and Meta-analysis of 34 Prospective Cohort Studies.

The aim of this study is to assess the association between midlife risk factors and dementia. PubMed and Cochrane library were systematically searched on May 24, 2018, to retrieve prospective cohort studies. The summary Relative Risk (RR) and 95% Confidence Interval (CI) were calculated by the random-effect model to explore the association between midlife risk factors and dementia. Sensitivity analysis and meta-regression were conducted to explore the source of heterogeneity. Publication bias was examined using Begg's and Egger's tests. Thirty-four prospective cohort studies were included, among which 24 were eligible for metaanalysis. A total of 159,594 non-demented adults were enrolled at baseline before 65 years and 13,540 people were diagnosed with dementia after follow-up. The pooled results revealed that five factors could significantly increase the dementia risk by 41 to 78%, including obesity (RR, 1.78; 95% CI: 1.31-2.41), diabetes mellitus (RR, 1.69; 95% CI: 1.38-2.07), current smoking (RR, 1.61; 95%, CI: 1.32-1.95), hypercholesterolemia (RR, 1.57; 95% CI: 1.19-2.07), and hypertension (borderline blood pressure RR, 1.41; 95% CI: 1.23-1.62 and high Systolic Blood Pressure (SBP) RR, 1.72; 95% CI: 1.25-2.37). However, the sensitivity analyses found that the results of hypercholesterolemia and high SBP were not reliable, which need to be confirmed by more high-quality studies. No influences due to publication bias were revealed. In the systematic review, another three factors (hyperhomocysteinemia, psychological stress, and heavy drinking) were found to be associated with elevated dementia risk. In addition, physical exercise, a healthy diet, and hormone therapy in middle age were associated with the reduction of dementia risk. Middle-aged people with obesity, diabetes, hypertension, or hypercholesterolemia, and current smokers in midlife are at higher risk of developing dementia later in life.

Spousal Influences on Monthly Disability in Late-Life Marriage in the Precipitating Events Project.

Few studies have examined spousal influences on disability in late-life marriage, and no prior study has examined these associations using monthly data. Drawing from interdependence theory, we hypothesized that one spouse currently having higher disability would be positively associated with their partner having higher disability in the next month. We also examined whether participants were at risk for increased disability when both spouses had higher prior disability. In addition, we examined gender differences in spousal associations. Data were from 37 married couples in the Precipitating Events Project, an ongoing longitudinal study of 754 initially nondisabled adults aged 70 years and older. Assessments included monthly disability (13 basic, instrumental, and mobility activities of daily living) and demographics. As hypothesized, higher disability in one spouse was positively associated with higher subsequent disability in their partner. Also, wives with higher disability were especially vulnerable to subsequent increased disability when husbands had higher disability. Incorporating a spouse's current disability level in modeling older adults' subsequent disability provides additional predictive information. Wives with greater disability may be at a particularly high risk of accelerated decline when their husbands have greater disability.

Association of peripheral inflammatory markers with connectivity in large-scale functional brain networks of non-demented older adults

BackgroundSystemic inflammation has emerged as a risk factor for cognitive decline and Alzheimer’s disease, but inflammation’s effect on distributed brain networks is unclear. We examined the relationship between peripheral inflammatory markers and subsequent functional connectivity within five large-scale cognitive networks and evaluated the modifying role of cortical amyloid and APOE ε4 status. MethodsBlood levels of soluble tumor necrosis factor-alpha receptor-1 and interleukin 6 were assessed in 176 participants (at baseline mean age: 65 (SD 9) years; 63% women; 85% cognitively normal, 15% mild cognitive impairment (MCI)) and were combined to derive an Inflammatory Index. Approximately six years later, participants underwent resting-state functional magnetic resonance imaging to quantify functional connectivity; a subset of 137 participants also underwent 11C Pittsburgh compound-B (PiB) PET imaging to assess cortical amyloid burden. ResultsUsing linear regression models adjusted for demographic characteristics and cardiovascular risk factors, a higher Inflammatory Index was associated with lower connectivity within the Default Mode (β = −0.013; 95% CI: −0.023, −0.003) and the Dorsal Attention Networks (β = −0.017; 95% CI: −0.028, −0.006). The strength of these associations did not vary by amyloid status (positive/negative). However, there was a significant interaction between Inflammatory Index and APOE ε4 status, whereby ε4-positive participants with a higher Inflammatory Index demonstrated lower connectivity. Inflammatory Index was unrelated to connectivity within other large-scale cognitive networks (Control, Limbic, and Salience/Ventral Attention networks). ConclusionPeripheral pro-inflammatory signaling in older adults without dementia, especially among APOE ε4-positive individuals, is associated with altered connectivity within two large-scale cognitive networks.

Associations of decision making abilities with blood pressure values in older adults.

Decision making, key to successful aging, has implications for financial success, physical health, and well being. While poor decision making has been linked with increased risk of mortality, age-related cognitive decline, and dementia, less is known regarding its associations with chronic disease indicators. We investigated the associations of decision making with blood pressure (BP) values [i.e., SBP, mean arterial pressure (MAP), and pulse pressure (PP), separately] in a community-based cohort study of aging. Participants were 908 nondemented older adults (age ∼81 years; 75% women) from the Rush Memory and Aging Project. Decision making was measured using questions designed to simulate materials used in financial and healthcare settings in the real world and yielded a total score and domain-specific health and financial decision making scores. Two seated and one standing BP measurement were taken with all three contributing to average SBP, MAP that is, [SBP + (2 × DBP)]/3, and PP, that is, SBP - DBP. Participants were queried about hypertension status and antihypertension medications were visually inspected and coded. Participants also underwent medical history and cognitive assessments. In separate multivariable linear regression models, total decision making scores were inversely associated with SBP, MAP, and PP after adjusting for age, sex, education, antihypertension medication use, diabetes, and cumulative cardiovascular disease burden (P values = 0.03). Decision making remained associated with these BP values after additional adjustment for global cognition. Poorer decision making is associated with higher BP values in nondemented older adults.