Nondemented Adults Research Articles

Context-Dependent Behavior in Parkinson’s Disease With Freezing of Gait

Background. Context-dependent behavior is a phenomenon in which people demonstrate superior performance in the context where a motor task was originally learned, but show poorer performance in an unfamiliar context. Previous studies found that people with Parkinson’s disease (PD) demonstrated greater context-dependency than nondisabled adults. Moreover, the frontostriatal circuit appeared to play a role in mediating context-dependent behavior. Neuroimaging studies showed that people with PD and freezing of gait (FoG) had difficulty recruiting the frontostriatal circuit when performing a set-shifting task, known to be mediated by this neural network. Objective. This study aimed to investigate whether individuals with PD and FoG (PD + FoG) would be more context-dependent than those without FoG (PD − FoG). Furthermore, the association between context-dependent behavior and set-shifting ability would be determined. Methods. Sixteen individuals with PD + FoG, 15 participants with PD − FoG, and 15 nondisabled adults (Control) were recruited. The participants practiced 3 numerical sequences, each associated with a specific context. One day following practice, the participants were tested under 2 conditions: the sequence-context associations remained the same as practice or were changed. Set-shifting ability was measured by the Trail Making Test (TMT). Results. Compared to the PD − FoG group, the PD + FoG group showed a greater decrement in normalized motor performance when the sequence-context associations were changed. Context-dependency correlated with the TMT in the PD − FoG group but not in the PD + FoG or Control groups. Conclusion. While people with PD + FoG appeared to be more context-dependent than individuals without FoG, a relationship between context-dependent behavior and set-shifting existed only in those without FoG.

Compensatory strategy use improves real-world functional performance in community dwelling older adults.

Compensatory strategies such as assistive technology, external reminders, and environmental cues may help support instrumental activities of daily living (IADLs) and independence. However, functional ability is most often evaluated in clinical settings where everyday compensation cannot be readily observed. The present study used a novel, real-world evaluation of everyday activities (prospective memory, household chores, complex IADLs, and planning tasks) to examine the impact of compensation. Fifty community dwelling older adults were recruited with cognitive status ranging from healthy to mildly impaired. Participants completed a battery of validated performance-based and cognitive tasks, an IADL questionnaire (also completed by an informant), and real-world activities carried out in their own homes. The real-world evaluation demonstrated adequate interrater reliability (intraclass coefficient = 0.92) and construct validity (r = 0.55). Compensation improved real-world task outcome on prospective memory and household chores tasks. Further, cognition emerged as a moderator between compensation and prospective memory task outcome. Participants' ratings on an IADL questionnaire were related to real-world and performance-based functioning whereas informants' ratings were related to performance-based tasks and cognition. Our results suggest that proxy measures of functional ability (i.e., performance-based, cognitive, and IADL questionnaire measures) do not fully capture the complexity of real-world performance for nondemented community dwelling older adults. Compensation appeared to improve prospective memory performance, particularly for individuals with average to low average cognitive abilities. A difference in IADL questionnaire ratings suggest that participants may be better able to judge their real-world performance than informants. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Normative Data for the Logical Memory Subtest of the Wechsler Memory Scale-IV in Middle-Aged and Elderly Korean People.

ObjectiveThe purpose of this study is to identify the demographic variables that are affecting performances on the Logical Memory (LM) subtest included in the Korean version of the Wechsler Memory Scale (WMS)-IV and to provide normative data on the LM subtest for the middle-age and elderly Korean people. MethodsThe participants were 435 non-demented adults aging from 50 to 90 and with the educational level ranging from 0 to 21 years. ResultsAge and education were found to be significantly associated with performance on the LM subtest, while gender effect was not statistically significant. Therefore, we stratified the norm blocks by age and education. Age was divided into three groups: 50–59, 60–74, and 75–90 years. Education was stratified into three groups: 0–8 years, 9–12 years, and 13 years or more. ConclusionThe normative data provided in the current study are expected to be useful in clinical and research settings to detect or define subtle changes in episodic memory in Korean adults and elderly, and can also be used for cross-cultural comparison of verbal episodic memory performance among elderly populations using different languages.

Coffee intake and decreased amyloid pathology in human brain

Several epidemiological and preclinical studies supported the protective effect of coffee on Alzheimer’s disease (AD). However, it is still unknown whether coffee is specifically related with reduced brain AD pathologies in human. Hence, this study aims to investigate relationships between coffee intake and in vivo AD pathologies, including cerebral beta-amyloid (Aβ) deposition, the neurodegeneration of AD-signature regions, and cerebral white matter hyperintensities (WMH). A total of 411 non-demented older adults were included. Participants underwent comprehensive clinical assessment and multimodal neuroimaging including [11C] Pittsburgh compound B-positron emission tomography (PET), [18F] fluorodeoxyglucose PET, and magnetic resonance imaging scans. Lifetime and current coffee intake were categorized as follows: no coffee or <2 cups/day (reference category) and ≥2 cups/day (higher coffee intake). Lifetime coffee intake of ≥2 cups/day was significantly associated with a lower Aβ positivity compared to coffee intake of <2 cups/day, even after controlling for potential confounders. In contrast, neither lifetime nor current coffee intake was not related to hypometabolism, atrophy of AD-signature region, and WMH volume. The findings suggest that higher lifetime coffee intake may contribute to lowering the risk of AD or related cognitive decline by reducing pathological cerebral amyloid deposition.

Cerebrospinal fluid and plasma neurofilament light relate to abnormal cognition

IntroductionNeuroaxonal damage may contribute to cognitive changes preceding clinical dementia. Accessible biomarkers are critical for detecting such damage. MethodsPlasma and cerebrospinal fluid (CSF) neurofilament light (NFL) were related to neuropsychological performance among Vanderbilt Memory & Aging Project participants (plasma n = 333, 73 ± 7 years; CSF n = 149, 72 ± 6 years) ranging from normal cognition (NC) to mild cognitive impairment (MCI). Models adjusted for age, sex, race/ethnicity, education, apolipoprotein E ε4 carriership, and Framingham Stroke Risk Profile. ResultsPlasma NFL was related to all domains (P values ≤ .008) except processing speed (P values ≥ .09). CSF NFL was related to memory and language (P values ≤ .04). Interactions with cognitive diagnosis revealed widespread plasma associations, particularly in MCI participants, which were further supported in head-to-head comparison models. DiscussionPlasma and CSF NFL (reflecting neuroaxonal injury) relate to cognition among non-demented older adults albeit with small to medium effects. Plasma NFL shows particular promise as an accessible biomarker with relevance to cognition in MCI.

Is Primary Care A Substitute or Complement for Other Medical Care? Evidence from Medicaid.

It is widely believed that Medicaid reimbursement for primary care is too low and that these low fees adversely affect access to healthcare for Medicaid recipients. In this article, we exploit changes in Medicaid physician fees for primary care to study the response of primary care visits and services that are complements/substitutes with primary care, including emergency department, hospitalization, prescription drugs, and imaging. Results from our study indicate that higher Medicaid fees for primary care have modest effects. Among non-blind and non-disabled adults, we find that a 25% (or $10) increase in Medicaid fees for primary care is associated with approximately a 5% of a standard deviation increase in the number of primary care visits. For the same group, we also find that the fee increase is associated with an increase in the probability of having any primary care visits of approximately 3 percentage points. For children, changes in Medicaid fees are not significantly related to the number of primary care visits. In terms of other types of care, we find some evidence that Medicaid fees for primary care are associated with prescription drug use, and no evidence that primary care fees are associated with the use of emergency department, inpatient services, or imaging. Overall, our evidence provides, at best, limited support for the large effects of Medicaid fees on service provision sometimes asserted in policy discussions.

Editors' note: Circulating cortisol and cognitive and structural brain measures: The Framingham Heart Study

Using cross-sectional data from the Framingham Heart Study including nondemented middle-aged adults, Echouffo-Tcheugui et al. identified an association between higher serum cortisol levels and lower brain volume and poorer performance on a variety of cognitive assessments. Although the serum cortisol measurement was acquired at a single point in time, and may not be reflective of chronic elevations in cortisol as Barbosa et al. assert, the data are strongly suggestive of a correlation. The investigators also agree that hair cortisol might be a better indicator of long-term cortisol levels; however, these data were not available in this observational cohort. Drs. Jimenez-Pavon and Carbonell-Baeza comment on the role that physical activity (PA) and cardiorespiratory fitness (CRF) may have on structural brain integrity and cognitive performance. Some of these associations from the Framingham Heart Study have been previously published in Neurology ® in 2016. Although analysis of these physiologic variables may be worthy of further investigation, Echouffo-Tcheugi et al. argue that PA and CRF may alter cortisol levels (and thereby, neural structure and function), but that such a mediation could lead to an overadjustment. Based on the results of this analysis, the investigators emphasize that cortisol levels may be the bridge the between PA/CRF and brain volume and cognitive performance. Using cross-sectional data from the Framingham Heart Study including nondemented middle-aged adults, Echouffo-Tcheugui et al. identified an association between higher serum cortisol levels and lower brain volume and poorer performance on a variety of cognitive assessments. Although the serum cortisol measurement was acquired at a single point in time, and may not be reflective of chronic elevations in cortisol as Barbosa et al. assert, the data are strongly suggestive of a correlation. The investigators also agree that hair cortisol might be a better indicator of long-term cortisol levels; however, these data were not available in this observational cohort. Drs. Jimenez-Pavon and Carbonell-Baeza comment on the role that physical activity (PA) and cardiorespiratory fitness (CRF) may have on structural brain integrity and cognitive performance. Some of these associations from the Framingham Heart Study have been previously published in Neurology ® in 2016. Although analysis of these physiologic variables may be worthy of further investigation, Echouffo-Tcheugi et al. argue that PA and CRF may alter cortisol levels (and thereby, neural structure and function), but that such a mediation could lead to an overadjustment. Based on the results of this analysis, the investigators emphasize that cortisol levels may be the bridge the between PA/CRF and brain volume and cognitive performance.

Neurofilament light chain plasma concentration predicts neurodegeneration and clinical progression in nondemented elderly adults.

Previous studies demonstrated that plasma neurofilament light chain (NFL) played important predictive roles in disease progression and neurodegeneration in the preclinical phase of familial Alzheimer’s disease (AD). However, whether plasma NFL has the same predictive roles in sporadic AD is still unclear. In this study, 243 cognitively normal (CN) participants from the ADNI database were divided into two subgroups (CN- and CN+) according to CSF Aβ or AV45-PET. Associations of baseline plasma NFL concentrations or rate of change in plasma NFL with longitudinal data on other biomarkers were tested by multivariate linear mixed effects models (LMEMs). Results showed that plasma NFL concentration and its rate of change were already abnormally high in the preclinical phase of AD. Plasma NFL was associated with three core AD-related biomarkers in preclinical phase. Baseline plasma NFL, but not its rate of change, played predictive roles in both cognitive decline (β = -0.0349, p = 0.0274) and hippocampal atrophy (β = -0.0351, p = 0.0088), especially for preclinical AD participants. In summary, these results indicated that baseline plasma NFL, but not its rate of change, may be a valuable noninvasive tool to assess neurodegeneration and predict longitudinal disease progression in preclinical AD individuals.

Gait variability indicates underlying focal gray matter atrophy in the brain of non-demented older adults

Gait variability indicates underlying focal gray matter atrophy in the brain of non-demented older adults

Microstructural Correlates and Laterality Effect of Prospective Memory in Non-Demented Adults with Memory Complaints

Background: An increasing number of studies suggest the importance of prospective memory (ProM) due to its functional relevance and sensitivity to neuropathology. However, its relevant neural substrates have not been sufficiently explored. Objectives: The present study aimed to investigate the relationship between structural connectivity and both objective and subjective ProM measures in a group of non-demented people with subjective memory complaints, and to examine the potential of ProM measures to detect the difference between subjective cognitive decline (SCD) and mild cognitive impairment (MCI) in the pre-dementia stage. Method: Thirty-sevennon-dementedparticipants aged above 50 years were recruited from an outpatient Neurology Clinic; 13 of them fulfilled the criteria of MCI and 24 of SCD. All subjects received comprehensive neuropsychological tests, including the adapted version of the Cambridge Prospective Memory Test, as well as the Taiwan version of the Prospective and Retrospective Memory Questionnaire. The diffusion tensor imaging technique with tract-based spatial statistics was applied to measure cerebral microstructural changes. Results: Time-based ProM performance was significantly correlated with microstructural integrity of the right superior longitudinal fasciculus, while the event-based one was associated with that of the left superior longitudinal fasciculus and the genu of the corpus callosum among all participants and in the SCD group. After controlling for age, the correlation remained significant between event-based ProM performance and the left superior longitudinal fasciculus among all participants and in the MCI group, as well as between event-based ProM performance and the genu among all participants. Although self-reported ProM failures in real life was associated with fiber disruption of the left superior longitudinal fasciculus among all participants and within the MCI group, an inverse relationship was also observed with that of the corpus callosum in the SCD group even after controlling for age. As compared to the SCD group, people with MCI performed significantly worse on time-based ProM tasks and reported more ProM failures in daily life. Conclusions: ProM was related to the integrity of interhemispheric commissural fibers and association fibers that connect the frontal lobe with posterior regions, with a task-specific laterality effect. Time-based ProM tasks and self-reported ProM questionnaire may be sensitive to early pathological cognitive deterioration, while the concomitant aging process and individual awareness level may respectively confound the results of evaluation.

Hippocampus Mediates the Effect of Emotional Support on Cognitive Function in Older Adults.

Despite strong evidence that emotional support has a protective effect on cognitive decline, the neural basis for how an individual's emotional support is associated with cognition is unknown. We investigated if the hippocampus mediates the relationship between emotional support and cognition in older adults. Four hundred and ten nondemented Korean older adults were classified into two groups according to their Medical Outcomes Study-Social Support Survey emotional support scores: the poor emotional support (score ≤ 25th percentile of entire sample) and normal emotional support (score > 25th percentile of entire sample) groups. Cognitive function was assessed using the Verbal Memory Score and Consortium to Establish a Registry for Alzheimer's Disease Assessment Packet Neuropsychological Assessment Battery total score (CERAD-TS). Left and right hippocampal volume were obtained using 3T T1-weighted magnetic resonance images. Mediation analyses were conducted. In the association of emotional support with Verbal Memory Score, left hippocampal volume played a mediating role (indirect effect = 0.40, SE = 0.21, bias-corrected 95% confidence interval = 0.04, 0.86). In the association of emotional support with CERAD-TS, both left (indirect effect = 0.82, SE = 0.45, bias-corrected 95% confidence interval = 0.09, 1.83) and right (indirect effect = 0.51, SE = 0.32, bias-corrected 95% confidence interval = 0.02, 1.24) HPVs played mediating roles. The hippocampus may mediate the association between emotional support and cognition. Higher levels of emotional support may be associated with better verbal memory and global cognition via larger HPV.

Dissociable age and memory relationships with hippocampal subfield volumes in vivo:Data from the Irish Longitudinal Study on Ageing (TILDA)

The heterogeneous specialisation of hippocampal subfields across memory functions has been widely shown in animal models. Yet, few in vivo studies in humans have explored correspondence between hippocampal subfield anatomy and memory performance in ageing. Here, we used a well-validated automated MR segmentation protocol to measure hippocampal subfield volumes in 436 non-demented adults aged 50+. We explored relationships between hippocampal subfield volume and verbal episodic memory, as indexed by word list recall at immediate presentation and following delay. In separate multilevel models for each task, we tested linearity and non-linearity of associations between recall performance and subfield volume. Fully-adjusted models revealed that immediate and delayed recall were both associated with cubic fits with respect to volume of subfields CA1, CA2/3, CA4, molecular layer, and granule cell layer of dentate gyrus; moreover, these effects were partly dissociable from quadratic age trends, observed for subiculum, molecular layer, hippocampal tail, and CA1. Furthermore, analyses of semantic fluency data revealed little evidence of robust associations with hippocampal subfield volumes. Our results show that specific hippocampal subfields manifest associations with memory encoding and retrieval performance in non-demented older adults; these effects are partly dissociable from age-related atrophy, and from retrieval of well-consolidated semantic categories.

An empirical evaluation of a hands-free computer interaction for users with motor disabilities.

Standard computer input devices such as a mouse or a keyboard are not well suited to the needs of users with severe motor disabilities in their interaction with standard computer interfaces. The emergence of contemporary human computer interfaces has allowed for the development of innovative solutions for hands-free Human-Computer Interaction (HCI), which can improve the quality and accessibility of Information and Communication Technology (ICT) for motor-impaired users. The objectives of this study were to design, develop and evaluate a solution for a hands-free HCI, based on the Emotiv EPOC+ device, which, among other capabilities, also enables controlling the computer with facial expressions and motion sensors. Ten non-disabled adults and eight adults with a severe motor disability participated in an experiment to evaluate the proposed HCI solution. Eighteen users completed six experimental tasks successfully using both their existing computer use approach as well as the proposed hands-free computer use approach. The times necessary to complete the tasks were measured and analyzed, along with users' subjective observations about the difficulty level of both computer use approaches. Users' perceptions about the new hands-free computer use approach were assessed as well. Although there were no significant differences in both user types regarding the difficulty level in completing the tasks, disabled users solved the tasks with less effort. Positive perceptions about perceived usefulness, ease of use, appropriateness of the technology, and satisfaction with the proposed solution for touchless interaction were assessed for both user types. Scores were significantly higher for disabled users in the case of measuring the perceived usefulness, perceived ease of use and satisfaction with the solution. This study showed that users with severe motor difficulties find new HCI less challenging compared to their existing computer use approach than the non-disabled who use standard HCI. When compared with non-disabled users, the disabled ones can be equally effective when confronted with a new HCI technology. Future work is needed to improve the proposed solution and to analyze the impact of different factors on users with motor disabilities and their adoption of an innovative technology for touchless interaction with a computer.

Differences in Subjective Cognitive Complaints Between Non-Demented Older Adults from a Memory Clinic and the Community.

Subjective cognitive complaints (SCCs) may represent an early cognitive marker of Alzheimer's disease (AD). There is a need to identify specific SCCs associated with an increased likelihood of underlying AD. Using the Questionnaire of Cognitive Complaints (QPC), we evaluated the pattern of SCCs in a clinical sample of non-demented older adults in comparison to cognitively healthy community-dwelling volunteers (HV). In total, 142 non-demented older adults from the Czech Brain Aging Study referred to two memory clinics for their SCCs were classified as having subjective cognitive decline (SCD, n = 85) or amnestic mild cognitive impairment (aMCI, n = 57) based on a neuropsychological evaluation. Furthermore, 82 age-, education-, and gender-matched HV were recruited. All subjects completed the QPC assessing the presence of specific SCCs in the last six months. Both SCD and aMCI groups reported almost two times more SCCs than HV, but they did not differ from each other in the total QPC score. Impression of memory change and Impression of worse memory in comparison to peers were significantly more prevalent in both SCD and aMCI groups in comparison to HV; however, only the latter one was associated with lower cognitive performance. The pattern of QPC-SCCs reported by SCD individuals was more similar to aMCI individuals than to HV. A complaint about memory change seems unspecific to pathological aging whereas a complaint about worse memory in comparison to peers might be one of the promising items from QPC questionnaire potentially reflecting subtle cognitive changes.

Cognitive dispersion is a sensitive marker for early neurodegenerative changes and functional decline in nondemented older adults.

Intraindividual cognitive variability (IIV), a measure of within-person variability across cognitive measures at a single time point, is associated with mild cognitive impairment (MCI) and Alzheimer's disease (AD). Little is known regarding brain changes underlying IIV, or the relationship between IIV and functional ability. Therefore, we investigated the association between IIV and cerebral atrophy in AD-vulnerable regions and everyday functioning in nondemented older adults. 736 Alzheimer's Disease Neuroimaging Initiative (ADNI) participants (285 cognitively normal [CN]; 451 MCI) underwent neuropsychological testing and serial MRI over 2 years. Linear mixed effects models examined the association between baseline IIV and change in entorhinal cortex thickness, hippocampal volume, and everyday functioning. Adjusting for age, sex, apolipoprotein E genotype, amyloid-β positivity, and mean level of cognitive performance, higher baseline IIV predicted faster rates of entorhinal and hippocampal atrophy, as well as functional decline. Higher IIV was associated with both entorhinal and hippocampal atrophy among MCI participants but selective vulnerability of the entorhinal cortex among CN individuals. IIV was associated with more widespread medial temporal lobe (MTL) atrophy in individuals with MCI relative to CN, suggesting that IIV may be tracking advancing MTL pathologic changes across the continuum of aging, MCI, and dementia. Findings suggest that cognitive dispersion may be a sensitive marker of neurodegeneration and functional decline in nondemented older adults. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Impact of ICARE Training Speed and Motor Assistance on Cardiovascular Response

Purpose: A motor-assisted elliptical, ICARE, is used to address walking and fitness goals; yet, only limited data guide understanding of the impact of ICARE training parameters (e.g., speed and motor assistance) on cardiovascular response. A repeated-measures design investigated the influence of 5 predetermined ICARE speeds (25, 35, 45, 55, and 65 revolutions per minute) and 2 motor-assistance levels (with and without assistance) on heart rate (HR), Borg ratings of perceived exertion (RPE), and blood pressure (BP). Methods: Ten healthy participants' HR, RPE, and BP were recorded during steady state Active Assist (ICARE's motor assisting leg movement) and Active Assist Plus exercise (without motor's assistance) at 5 speeds. Results: Significant main effects on HR were documented for ICARE speed (F[4,36] = 77.313, P &lt; .001) and motor assistance (F[1,36] = 224.813, P &lt; .001), and an interaction (F[4,36] = 4.410, P = .005). Significant main effects on RPE were documented for speed (F[4,36] = 47.106, P &lt; .001) and motor assistance (F[1,36] = 24.929, P &lt; .001). Significant main effects on systolic BP were documented for speed (F[4,36] = 78.849, P &lt; .001) and motor assistance (F[1,36] = 6.911, P = .027), and an interaction (F[4,36] = 5.695, P = .001). Only the main effect of motor assistance on diastolic BP was significant (F[1,36] = 7.917, P = .020). Conclusions: Increases in ICARE speed and decreases in motor assistance contributed to clinically relevant increases in HR, RPE, and systolic BP in a cohort of young, nondisabled adults.

THE ASSOCIATION BETWEEN APOE ε4 AND AGE-RELATED RESTING STATE FUNCTIONAL CONNECTIVITY IN A COMMUNITY-BASED SAMPLE OF RACIALLY/ETHNICALLY DIVERSE OLDER ADULTS

Several studies have reported age-related alterations in resting-state functional connectivity of the default mode network (DMN), but we lack an understanding of the mechanisms underlying these functional changes. Further, epidemiological and genome-wide association studies suggest that Alzheimer's disease (AD) may manifest differently according to race and susceptibility genes. For example, Apolipoprotein E (APOE) ε4 is a known risk factor of AD, but notably, the relationship between APOE e4 and AD differs across race and ethnicity. No study to date has examined whether race/ethnicity and APOE status moderate the relationship between age and DMN connectivity. We determined whether APOE status moderates the relationship between age and DMN connectivity in a community-based sample of racially/ethnically diverse older adults from the Washington Heights-Inwood Community Aging Project (WHICAP) study. Participants were 383 non-demented (35% White, 34% Black, 31% Hispanic; M age=74yrs SD=6; 56% women) older adults in a longitudinal aging study, who underwent a neuropsychological evaluation and 3T MRI scanning. We used linear regression models with intra-network connectivity between midline (hippocampus) and posterior (posterior cingulate) nodes of the DMN as dependent variables. Age, APOE status (ε4 present or absent), race/ethnicity, and the interaction between APOE status and age were independent variables; the models adjusted for sex/gender and recruitment cohort. Increased age was associated with reduced functional connectivity (main effect of age, β=−.001, [−.006, .003]). APOE ε4+ participants showed greater age-related decline in DMN connectivity (APOE and age interaction, β=−.010,[−.017,−.002]) . Stratified by race/ethnicity this effect was largest in Hispanics (β=−.018,[−.036,0]), compared with Blacks (β=−.011,[−.025,.003]), and Whites (β=−.010,[−.024,.004]). APOE status moderated age-related differences in resting state functional connectivity. Nevertheless, this relationship was similar across race/ethnicity. Future analyses will examine age-related changes in other modalities of brain health (e.g., white matter integrity, grey matter volume, cortical thickness) to investigate the role of APOE in racially/ethnically diverse older adults.

SEMANTIC CLUSTERING ON THE C.V.L.T.-II IS REDUCED IN COGNITIVELY INTACT OLDER ADULTS WITH AUTOPSY-CONFIRMED ALZHEIMER’S DISEASE NEUROPATHOLOGIC CHANGE

Semantic clustering (SC) is a learning strategy of grouping information with shared attributes and is measured on memory such tests as the California Verbal Learning Test-II (CVLT). Recent research suggests that reductions in SC parallel clinical progression in Alzheimer's disease (AD) such that SC for intact individuals is greater than mild cognitive impairment which is greater than dementia. The objective of the present study was to examine SC in an autopsy cohort, longitudinally. It was hypothesized that participants with greater AD pathology who show reduced SC over time. Participants were older adults, cognitively intact at baseline, never demented, and came to autopsy after ≥3 years of annual CVLT administrations. Brain autopsies followed standardized protocols. Braak staging was used to classify participants for analysis: AD- (Braak 1-3) and AD+ (4-6). Linear mixed models (LMMs) controlling for age, sex, and education were used to examine total learning trial SC (z-scores) longitudinally with a group × administration interaction. 39 participants were classified as AD- and 10 as AD+. The groups (AD-, AD+) were statistically similar in age at baseline (79.1y, 80.4y), education (16y, 17.5y), sex (20F, 4F), age at death (86.4y, 87y), post mortem interval (4.8hrs, 10.5hrs), and administrations (4.9y, 5.4y), ps > 0.19. A LMM indicated that the AD+ group exhibited reduced SC at each CVLT administration (β = −0.20, p = 0.05). Excluding one AD+ participant with a precipitous decline in SC nullified the group × administration interaction but the AD+ group exhibited significantly reduced SC compared to the AD- group (β = −1.02, p = 0.021) at all administrations. The results demonstrate that SC is reduced in non-demented older adults with autopsy-confirmed AD. Although we hypothesized a reduction in SC over time, it appears that SC was reduced prior to clinical indication of cognitive decline. This is in line with evidence that AD pathology accumulates gradually over the span of years. A small, well-educated cohort limits the generalizability of this study; but, it provides evidence that SC may offer an indicator of preclinical AD using a widely-available neuropsychological test.

APOLIPOPROTEIN ε4 STATUS, SEX DIFFERENCES, AND OLFACTORY RECOGNITION MEMORY: AN FMRI STUDY

The Apolipoprotein (ApoE) ε4 allele is the strongest known genetic risk factor for Alzheimer's disease (AD; Lind et al., 2006). Olfactory impairment is one of the earliest signs of AD (Albers et al., 2014). To our knowledge, no previous study has examined the interaction of sex and ApoE ε4 status in differential olfactory memory processing utilizing neuroimaging data within elderly individuals. The present study investigates olfactory memory task performance while ApoE ε4 carriers and non-carriers completed a functional magnetic resonance imaging (fMRI) and structural scan. Participants were (N = 39) non-demented older adults, ranging in age from 64 to 88 years. Individuals with at least one ε4 allele were classified as ε4 carriers (n = 18). Individuals without the ε4 allele (n = 21) were classified as non-carriers. Prior to the fMRI scan, participants were presented with 16 odors from the California Odor Learning Test (COLT; Murphy et al., 1997). During the scan, participants were presented with labels of odors and asked to decide if the label was presented prior to the scan (target) or not (foil). ε4 carriers demonstrated significantly (p < .05) greater atrophy in the left cingulate cortex when compared to ε4 non-carriers. Regression analyses revealed that for ε4 carriers average rates for correctly identifying a target (hit) were positively associated with cingulate cortex thickness. While committing hits, male ApoE ε4 carriers demonstrated significantly (p < .015) greater activation in the right parahippocampal gyrus, right hippocampus, and precuneus when compared to female e4 carriers.

Gait Abnormalities and the Risk of Falls in CKD.

Older adults with CKD are at high risk of falls and disability. It is not known whether gait abnormalities contribute to this risk. Quantitative and clinical gait assessments were performed in 330 nondisabled community-dwelling adults aged ≥65 years. CKD was defined as an eGFR <60 ml/min per 1.73 m2. Cox proportional hazards models were created to examine fall risk. A total of 41% (n=134) of participants had CKD. In addition to slower gait speed, participants with CKD had gait cycle abnormalities including shorter stride length and greater time in the stance and double-support phases. Among people with CKD, lower eGFR was independently associated with the severity of gait cycle abnormalities (per 10 ml/min per 1.73 m2 lower eGFR: 3.6 cm [95% confidence interval (95% CI), 1.4 to 5.8] shorter stride length; 0.7% [95% CI, 0.3 to 1.0] less time in swing phase; 1.1% [95% CI, 0.5 to 1.7] greater time in double-support phase); these abnormalities mediated the association of lower eGFR with slower gait speed. On clinical gait exam, consistent with the quantitative abnormalities, short steps and marked swaying or loss of balance were more common among participants with CKD, yet most had no identifiable gait phenotype. A gait phenotype defined by any of these abnormal signs was associated with higher risk of falls among participants with CKD: compared with people without CKD and without the gait phenotype, the adjusted hazard ratio was 1.72 (95% CI, 1.06 to 2.81) for those with CKD and the phenotype; in comparison, the adjusted hazard ratio was 0.71 (95% CI, 0.40 to 1.25) for people with CKD but without the phenotype (P value for interaction of CKD status and gait phenotype =0.01). CKD in older adults is associated with quantitative gait abnormalities, which clinically manifest in a gait phenotype that is associated with fall risk.