Small vessel cerebrovascular disease is associated with cognition in prospective Alzheimer's clinical trial participants.

BACKGROUND: Secondary prevention clinical trials for Alzheimer's disease (AD) target amyloid accumulation in asymptomatic, amyloid-positive individuals, but it is unclear to what extent other pathophysiological processes, such as small vessel cerebrovascular disease, account for participant performance on the primary cognitive outcomes in those trials. White matter hyperintensities are areas of increased signal on T2-weighted magnetic resonance imaging (MRI) that reflect small vessel cerebrovascular disease. They are associated with cognitive functioning in older adults and with clinical presentation and course of AD, particularly when distributed in posterior brain regions. The purpose of this study was to examine to what degree regional WMH volume is associated with performance on the primary cognitive outcome measure in the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) study, a secondary prevention trial. METHODS: Data from 1791 participants (59.5% women, mean age (SD) 71.6 (4.74)) in the A4 study and the Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN) companion study at the screening visit were used to quantify WMH volumes on T2-weighted fluid-attenuated inversion recovery (FLAIR) MR images. Cognition was assessed with the preclinical Alzheimer cognitive composite (PACC). We tested the association of total and regional WMH volumes with PACC performance, adjusting for age, education, and amyloid positivity status, with general linear models. We also considered interactions between WMH and amyloid positivity status. RESULTS: Increased frontal and parietal lobe WMH volume was associated with poorer performance on the PACC. While amyloid positivity was also associated with lower cognitive test scores, WMH volumes did not interact with amyloid positivity status. CONCLUSION: These results highlight the potential of small vessel cerebrovascular disease to drive AD-related cognitive profiles. Measures of small vessel cerebrovascular disease should be considered when evaluating outcome in trials, both as potential effect modifiers and as a possible target for intervention or prevention.

The effects of insufficient sleep and adequate sleep on cognitive function in healthy adults.

STUDY OBJECTIVES: Although sleep affects a range of waking behaviors, the majority of studies have focused on sleep loss with relatively little attention on sustained periods of adequate sleep. The goal of this study was to use an experimental design to examine the effect of both of these sleep patterns on cognitive performance in healthy adults. METHODS: This study used a randomized crossover design. Participants who regularly slept 7-9 hours/night completed two 6-week intervention conditions, adequate sleep (maintenance of habitual bed/wake times) and insufficient sleep (reduction in sleep of 1.5 hours relative to adequate sleep), separated by a 2-6weeks (median=43days) washout period. Cognitive functioning was evaluated at baseline and endpoint of each intervention using the NIH Toolbox Cognition Battery. General linear models contrasted scores following each condition to the baseline of the first condition; the baseline of the second condition was included to evaluate practice effects. RESULTS: Sixty-five participants (age 35.9 ± 4.9years, 89% women, 52% non-White race/ethnicity) completed study procedures. There was improvement in performance on the List Sorting Working Memory task after the adequate sleep condition that exceeded practice effects. Cognitive performance after insufficient sleep did not reach the level expected with practice and did not differ from baseline. A similar pattern was found on the Flanker Inhibitory Control and Attention task. CONCLUSIONS: These findings contribute to our understanding of the complex interplay between sleep and cognition and demonstrate that consistent, stable sleep of at least 7 hours/night improves working memory and response inhibition in healthy adults. CLINICAL TRIAL REGISTRATION: The manuscript reports on data from two clinical trials: Impact of Sleep Restriction on Performance in Adults (URL: https://clinicaltrials.gov/ct2/show/NCT02960776, ID Number: NCT02960776) and Impact of Sleep Restriction in Women (URL: https://clinicaltrials.gov/ct2/show/NCT02835261, ID Number: NCT02835261).

Age of first exposure to soccer heading: Associations with cognitive, clinical, and imaging outcomes in the Einstein Soccer Study.

Introduction: The objective of this study is to assess the role of age at first exposure (AFE) to soccer heading as a predictor of known adverse associations of recent and longer-term heading with brain microstructure, cognitive, and behavioral features among adult amateur soccer players. Methods: The sample included 276 active amateur soccer players (196 male and 81 female) aged 18-53 years old. AFE to soccer heading was treated as a binary variable, dichotomized at ≤ 10 years vs. >10 years old, based on a recently promulgated US Soccer policy, which bans heading for athletes ages 10 and under. Results: We found that soccer players who began heading at age 10 or younger performed better on tests of working memory (p = 0.03) and verbal learning (p = 0.02), while accounting for duration of heading exposure, education, sex, and verbal intelligence. No difference in brain microstructure or behavioral measures was observed between the two exposure groups. Discussion: The findings indicate that, among adult amateur soccer players, AFE to heading before age 10 compared to later start of heading, is not associated with adverse outcomes, and may be associated with better cognitive performance in young adulthood. Cumulative heading exposure across the lifespan, rather than early life exposure, may drive risk for adverse effects and should be the focus of future longitudinal studies to inform approaches to enhance player safety.

Cortical thickness and hippocampal volume in adolescent children with obstructive sleep apnea.

STUDY OBJECTIVES: Intermittent hypoxia and sleep fragmentation due to obstructive sleep apnea (OSA) may contribute to oxidative tissue damage and apoptotic neuronal cell death, inflammation, and intracellular edema in the brain. We examined whether OSA in overweight and obese adolescent children is associated with cortical thickness and hippocampal structure compared to overweight and obese controls and whether OSA severity is associated with measures of brain integrity. METHODS: We calculated cortical thickness and hippocampal subfield volumes from T1-weighted images of 45 controls (age 15.43 ±â€…1.73 years, 21 male) and 53 adolescent children with OSA (age 15.26 ±â€…1.63 years, 32 male) to investigate the association of childhood OSA with the alteration of cortical structure and hippocampal subfield structural changes. In addition, we investigated the correlation between OSA severity and cortical thickness or hippocampal subfield volume using Pearson's correlation analysis. RESULTS: We found cortical thinning in the right superior parietal area of adolescent children with OSA (cluster size 32.29 mm2, cluster-wise corrected p-value = .030) that was negatively correlated with apnea-hypopnea index (AHI) (R=-0.27, p-value = .009) and arousal index (R=-0.25, p-value = .014). In addition, the volume of the right subiculum-head area of the hippocampus of adolescent children with OSA was larger than controls (0.19 ±â€…0.02 ml vs. 0.18 ±â€…0.02 ml, ß = 13.79, false discovery rate corrected p-value = .044), and it was positively correlated with AHI (R = 0.23, p-value = .026) and arousal index (R = 0.31, p-value = .002). CONCLUSIONS: Our findings provide evidence for OSA-associated brain structure alterations in adolescent children prior to the onset of treatment that likely have important implications for timely intervention and continued monitoring of health outcomes.

Repetitive soccer heading adversely impacts short-term learning among adult women.

OBJECTIVES: To determine the impact of 12-month heading exposure on short-term learning. DESIGN: A total of 105 active amateur soccer players, 45 women and 60 men, were administered an EMA-based test of working memory, a version of the two-back, once daily for 14 days. METHODS: Heading exposure of the participants was assessed using "HeadCount", a validated structured questionnaire at the baseline visits. The short-term rate of learning of each individual is quantified by first fitting a quadratic model to the daily performance on the two-back test over a two-week period, then taking the instantaneous rate of the quadratic function at the 7th test. A linear regression model was used to test the association of heading exposure with rates of learning, including age, sex, years of education and history of concussion as covariates, as well as variables describing soccer play and heading within the two-week period. Sensitivity analyses were performed using different methods for quantifying the learning effects and different transformations on 12-month heading exposure. RESULTS: Greater 12-month heading was associated with lower rates of learning among women (p = 0.008) but not among men (p = 0.74). CONCLUSIONS: We have identified evidence for an adverse, albeit subclinical, effect of soccer heading on brain function among young adult players, which selectively affects women in our sample.

Obstructive sleep apnea, cerebrovascular disease, and amyloid in older adults with Down syndrome across the Alzheimer's continuum.

We determined the extent to which obstructive sleep apnea (OSA) is associated with increased cerebrovascular disease and amyloid burden, and the relation of the two processes across clinical Alzheimer's disease (AD) diagnostic groups in adults with Down syndrome (DS). Adults with DS from the Biomarkers of Alzheimer's Disease in Down Syndrome (ADDS) study were included given available research MRI (n = 116; 50 ± 8 years; 42% women) and amyloid PET scans (n = 71; 50 ± 7 years; 39% women) at the time of analysis. Participants were characterized as cognitively stable (CS; 64%), with mild cognitive impairment-DS (MCI-DS; 23%), with possible AD dementia (5%), or with definite AD dementia (8%). OSA was determined via medical records and interviews. Models tested the effect of OSA on MRI-derived cerebrovascular biomarkers and PET-derived amyloid burden, and the moderating effect of OSA and AD diagnosis on biomarkers. OSA was reported in 39% of participants, which did not differ by clinical AD diagnostic group. OSA was not associated with cerebrovascular biomarkers but was associated with greater cortical amyloid burden. White matter hyperintensity (WMH) volume (primarily in the parietal lobe), enlarged perivascular spaces, and cortical and striatal amyloid burden were greater across clinical AD diagnostic groups (CS

Altered cortical structure network in children with obstructive sleep apnea.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is characterized by recurrent airway collapse during sleep, resulting in intermittent hypoxia and sleep fragmentation that may contribute to alternations in brain structure and function. We hypothesized that OSA in children reorganizes and alters cortical structure, which can cause changes in cortical thickness correlation between brain regions across subjects. METHODS: We constructed cortical structure networks based on cortical thickness measurements from 41 controls (age 15.54 ±â€…1.66 years, male 19) and 50 children with OSA (age 15.32 ±â€…1.65 years, male 29). The global (clustering coefficient [CC], path length, and small-worldness) and regional (nodal betweenness centrality, NBC) network properties and hub region distributions were examined between groups. RESULTS: We found increased CCs in OSA compared to controls across a wide range of network densities (p-value < .05) and lower NBC area under the curve in left caudal anterior cingulate, left caudal middle frontal, left fusiform, left transverse temporal, right pars opercularis, and right precentral gyri (p-value < .05). In addition, while most of the hub regions were the same between groups, the OSA group had fewer hub regions and a different hub distribution compared to controls. CONCLUSIONS: Our findings suggest that children with OSA exhibit altered global and regional network characteristics compared to healthy controls. Our approach to the investigation of cortical structure in children with OSA could prove useful in understanding the etiology of OSA-related brain functional disorders.

Probing the proteome to explore potential correlates of increased Alzheimer's-related cerebrovascular disease in adults with Down syndrome.

Cerebrovascular disease is associated with symptoms and pathogenesis of Alzheimer's disease (AD) among adults with Down syndrome (DS). The cause of increased dementia-related cerebrovascular disease in DS is unknown. We explored whether protein markers of neuroinflammation are associated with markers of cerebrovascular disease among adults with DS. Participants from the Alzheimer's disease in Down syndrome (ADDS) study with magnetic resonance imaging (MRI) scans and blood biomarker data were included. Support vector machine (SVM) analyses examined the relationship of blood-based proteomic biomarkers with MRI-defined cerebrovascular disease among participants characterized as having cognitive decline (n = 36, mean age ± SD = 53 ± 6.2) and as being cognitively stable (n = 78, mean age = 49 ± 6.4). Inflammatory and AD markers were associated with cerebrovascular disease, particularly among symptomatic individuals. The pattern suggested relatively greater inflammatory involvement among cognitively stable individuals and greater AD involvement among those with cognitively decline. The findings help to generate hypotheses that both inflammatory and AD markers are implicated in cerebrovascular disease among those with DS and point to potential mechanistic pathways for further examination.

The Rapid Naming Test: Development and initial validation in typically aging adults.

ObjectiveProgressive word-finding difficulty is a primary cognitive complaint among healthy older adults and a symptom of pathological aging. Classic measures of visual confrontation naming, however, show ceiling effects among healthy older adults. To address the need for a naming test that is sensitive to subtle, age-related word-finding decline, we developed the Rapid Naming Test (RNT), a computerized, one-minute, speeded visual naming test.MethodFunctionally intact older (n = 145) and younger (n = 69) adults completed the RNT. Subsets of older adults also completed neuropsychological tests, a self-report scale of functional decline, amyloid-ß PET imaging, and repeat RNT administration to determine test-retest reliability.ResultsRNT scores were normally distributed and exhibited good test-retest reliability. Younger adults performed better than older adults. Within older adults, lower scores were associated with older age. Higher scores correlated with measures of language, processing speed, and episodic learning and memory. Scores were not correlated with visuospatial or working memory tests. Worse performance was related to subjective language decline, even after controlling for a classic naming test and speed. The RNT was also negatively associated with amyloid-ß burden.ConclusionsThe RNT appears to be a reliable test that is sensitive to subtle, age-related word-finding decline. Convergent and divergent validity are supported by its specific associations with measures relying on visual naming processes. Ecological validity is supported by its relationship with subjective real-world language difficulties. Lastly, worse performance was related to amyloid-ß deposition, an Alzheimer's disease biomarker. This study represents a key step toward validating a novel, sensitive naming test in typically aging adults.

Variable objective sleep quality is related to worse spatial learning and memory in young adults.

OBJECTIVE: The majority of research on sleep and cognition has focused on mean markers of sleep across multiple nights; however, variable sleep patterns have become increasingly common in the modern era. The purpose of this study was to examine whether objective intraindividual variability in sleep quantity and quality are related to verbal and visuospatial learning and memory functioning in young adults. METHODS: A total of 218 young adult college students were recruited from a university in the Eastern United States, among which 187 participants (70.6% female; mean age = 20.5, SD = 1.5) had complete actigraphy and cognitive performance data. Objective intraindividual means and variabilities of sleep quantity (total sleep time) and sleep quality (percent wake after sleep onset) were measured over a 1- to 2-week timeframe using wrist actigraphy. Verbal and visuospatial learning and memory were assessed using the International Shopping List and Groton Maze Learning tests of the Cogstate computerized test battery. RESULTS: Greater intraindividual variability in actigraphy-derived sleep quality was associated with poorer visuospatial learning and memory performance after controlling for mean sleep quality and visuomotor attention and processing speed (ps < 0.05). Actigraphic measures of sleep quantity were not related to any learning and memory measures. CONCLUSION: In young adults, intraindividual variability in objective sleep quality was significantly related to visuospatial learning and memory, over and above mean sleep quality. Given these associations, future studies should aim to identify modifiable lifestyle and environmental factors contributing to variable sleep quality.

Cognitive Functioning of Glucocerebrosidase (GBA) Non-manifesting Carriers.

Mutations and variants in the glucocerebrosidase (GBA) gene are among the most common genetic risk factors for the development of Parkinson's disease (PD). Yet, penetrance is markedly reduced, and less is known about the burden of carrying a single mutation among those without diagnosed PD. Motor, cognitive, psychiatric, and olfactory functioning were assessed in 30 heterozygous GBA mutation carriers without PD (the majority of whom had mild GBA mutations) and 49 non-carriers without PD. Study focus was on domains affected in GBA mutation carriers with PD, as well as those previously shown to be abnormal in GBA mutation carriers without PD. GBA mutation carriers showed poorer performance on the Stroop interference measure of executive functioning when controlling for age. There were no group differences in verbal memory, Montreal Cognitive Assessment (MoCA), overall motor score, or presence of REM sleep behavior disorder or depression. Although total olfaction scores did not differ, GBA mutation carriers with hyposmia had lower global cognition scores than those without hyposmia. As anticipated by the low penetrance of GBA mutations, these findings suggest that pre-manifest non-motor or motor features of PD may not present in most GBA mutation carriers. However, there is support that there may be a subtle difference in executive functioning among some non-manifesting heterozygous GBA mutation carriers, and, combined with olfaction, this may warrant additional scrutiny as a potential biomarker for pre-manifest and pre-clinical GBA related PD.

T-MoCA: A valid phone screen for cognitive impairment in diverse community samples.

INTRODUCTION: There is an urgent need to validate telephone versions of widely used general cognitive measures, such as the Montreal Cognitive Assessment (T-MoCA), for remote assessments. METHODS: In the Einstein Aging Study, a diverse community cohort (n = 428; mean age = 78.1; 66% female; 54% non-White), equivalence testing was used to examine concordance between the T-MoCA and the corresponding in-person MoCA assessment. Receiver operating characteristic analyses examined the diagnostic ability to discriminate between mild cognitive impairment and normal cognition. Conversion methods from T-MoCA to the MoCA are presented. RESULTS: Education, race/ethnicity, gender, age, self-reported cognitive concerns, and telephone administration difficulties were associated with both modes of administration; however, when examining the difference between modalities, these factors were not significant. Sensitivity and specificity for the T-MoCA (using Youden's index optimal cut) were 72% and 59%, respectively. DISCUSSION: The T-MoCA demonstrated sufficient psychometric properties to be useful for screening of MCI, especially when clinic visits are not feasible.

Framing potential for adverse effects of repetitive subconcussive impacts in soccer in the context of athlete and non-athlete controls.

The benefits of athletic activity may be attenuated by sport-related head impacts, including soccer-related concussion and subconcussive events. The purpose of this study is to characterize the specific effects of soccer heading on white matter microstructure and cognitive function, independent of concussion, relative to non-athlete controls and relative to active athletes who are not involved in collision sports. 246 amateur soccer players, 72 non-contact/non-collision sports athletes and 110 healthy,non-athlete controls were included in the study, and underwent cognitive testing and 3T diffusion tensor imaging (DTI). Voxelwise linear regression, comparing soccer players and non-contact/non-collision sports athletes healthy,non-athlete controls, identified regions of abnormally low and high fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD) and mean diffusivity (MD) in athlete participants. Generalized estimating equations were used to examine the effects of 2 week and 1 year heading exposure quartile on cognitive performance and on the volume of each high and each low DTI parameter. Athletes with no or lower exposure to repetitive heading exhibited greater expression of low RD, greater expression of high FA and better performance on tasks of attention, processing speed, verbal memory, and working memory compared to non-athletes. Soccer players with the highest exposure to repetitive head impacts, however, did not differ significantly from healthy, non-athletes on either micro-structural features or cognitive performance, findings not explained by concussion history or demographic factors. These results are consistent with the notion that beneficial effects of athletic conditioning or training on brain structure and function may be attenuated by exposure to repeated subconcussive head impacts.

Cerebrovascular disease promotes tau pathology in Alzheimer's disease.

Small vessel cerebrovascular disease, visualized as white matter hyperintensities on T2-weighted magnetic resonance imaging, contributes to the clinical presentation of Alzheimer's disease. However, the extent to which cerebrovascular disease represents an independent pathognomonic feature of Alzheimer's disease or directly promotes Alzheimer's pathology is unclear. The purpose of this study was to examine the association between white matter hyperintensities and plasma levels of tau and to determine if white matter hyperintensities and tau levels interact to predict Alzheimer's disease diagnosis. To confirm that cerebrovascular disease promotes tau pathology, we examined tau fluid biomarker concentrations and pathology in a mouse model of ischaemic injury. Three hundred ninety-one participants from the Alzheimer's Disease Neuroimaging Initiative (74.5 ± 7.1 years of age) were included in this cross-sectional analysis. Participants had measurements of plasma total-tau, cerebrospinal fluid beta-amyloid, and white matter hyperintensities, and were diagnosed clinically as Alzheimer's disease (n = 97), mild cognitive impairment (n = 186) or cognitively normal control (n = 108). We tested the relationship between plasma tau concentration and white matter hyperintensity volume across diagnostic groups. We also examined the extent to which white matter hyperintensity volume, plasma tau, amyloid positivity status and the interaction between white matter hyperintensities and plasma tau correctly classifies diagnostic category. Increased white matter hyperintensity volume was associated with higher plasma tau concentration, particularly among those diagnosed clinically with Alzheimer's disease. Presence of brain amyloid and the interaction between plasma tau and white matter hyperintensity volume distinguished Alzheimer's disease and mild cognitive impairment participants from controls with 77.6% and 63.3% accuracy, respectively. In 63 Alzheimer's Disease Neuroimaging Initiative participants who came to autopsy (82.33 ± 7.18 age at death), we found that higher degrees of arteriosclerosis were associated with higher Braak staging, indicating a positive relationship between cerebrovascular disease and neurofibrillary pathology. In a transient middle cerebral artery occlusion mouse model, aged mice that received transient middle cerebral artery occlusion, but not sham surgery, had increased plasma and cerebrospinal fluid tau concentrations, induced myelin loss, and hyperphosphorylated tau pathology in the ipsilateral hippocampus and cerebral hemisphere. These findings demonstrate a relationship between cerebrovascular disease, operationalized as white matter hyperintensities, and tau levels, indexed in the plasma, suggesting that hypoperfusive injury promotes tau pathology. This potential causal association is supported by the demonstration that transient cerebral artery occlusion induces white matter damage, increases biofluidic markers of tau, and promotes cerebral tau hyperphosphorylation in older-adult mice.

The Impact of Sleep on the Relationship between Soccer Heading Exposure and Neuropsychological Function in College-Age Soccer Players.

OBJECTIVE: Soccer is the most popular sport worldwide and is the only sport where athletes purposely use their head to deflect the ball during play, termed "heading" the ball. These repetitive head impacts (RHI) are associated with worse neuropsychological function; however, factors that can increase risk of injury following exposure to such head impacts have been largely unexamined. The present study provided a novel examination of the modifying role of sleep on the relationship between RHI exposure and neuropsychological function in college-age soccer players. METHODS: Fifty varsity and intramural college soccer players completed questionnaires assessing recent and long-term heading exposure, a self-report measure of sleep function, and a battery of neuropsychological tests. RESULTS: A high level of recent heading exposure was significantly associated with poorer processing speed, independent of concussion history. With reduced sleep duration, a high level of recent heading exposure was related to worse sustained attention. However, with greater hours of sleep duration, heading exposure was related to preserved neuropsychological outcome in sustained attention. CONCLUSIONS: We replicated our earlier finding of an association between recent head impact exposure and worse processing speed in an independent sample. In addition, we found that sleep may serve as a risk or protective factor for soccer players following extensive exposure to head impacts. Ultimately, this study furthers the understanding of factors impacting neuropsychological function in soccer players and provides empirical support for sleep interventions to help ensure safer soccer play and recovery from injury.

Personality and Risk Taking in Sports: A Focus on Unintentional and Intentional Head Impacts in Amateur Soccer Players.

OBJECTIVE: In soccer, unintentional and intentional (heading) head impacts are associated with concussive symptoms and cognitive dysfunction. We examined whether personality traits were associated with these behaviors in soccer players. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: Participants completed study visits at the Albert Einstein College of Medicine. A total of 307 adult amateur soccer players, recruited from New York City and the surrounding area, completed 737 HeadCount-2w questionnaires. PREDICTOR VARIABLES: Personality traits (intellect/imagination, conscientiousness, extraversion, agreeableness, and neuroticism) were assessed with the Mini-International Personality Item Pool questionnaire at the baseline study visit. MAIN OUTCOME MEASURES: Participants completed an online questionnaire (HeadCount-2w) to ascertain frequency of intentional head impacts and occurrence of unintentional head impacts every 3 to 6 months. Generalized estimating equations repeated-measures regressions determined whether personality predicted unintentional and intentional impacts. RESULTS: Personality traits were not associated with unintentional head impact(s) or frequency of intentional head impacts. CONCLUSIONS: These findings have important clinical implications, suggesting that personality is not driving the association between high levels of unintentional and intentional head impacts and worse neuropsychological functioning and concussive symptoms.

Health-related Quality of Life, Cognitive Performance, and Incident Dementia in a Community-based Elderly Cohort.

BACKGROUND: We hypothesized that higher quality of life would be associated with better cognitive function and a reduced risk of incident all cause dementia and Alzheimer disease (AD) in older adults. MATERIALS AND METHODS: Participants included 1183 older adults with an average age of 78.2 (SD=5.3) from Einstein Aging Study. The 36-Item Short-Form Health Survey was used to measure health-related quality of life (HRQoL). We investigated baseline associations between the cognitive domains of memory, executive function, and general fluid ability with 8 subscales of the 36-Item Short-Form Health Survey (physical functioning, role limitations due to physical problems, bodily pain, general health perceptions, social functioning, role limitations due to emotional problems, vitality, and general mental health) and the 2 component summary scores of physical component summary (PCS) and mental component summary (MCS). Next, we used Cox proportional hazard models to assess the predictive validity of HRQoL subscales for the onset of incident dementia and incident AD. RESULTS: At baseline, higher scores (better HRQoL) on MCS and its 4 subscales (social functioning, role limitations due to emotional problems, vitality, and general mental health) were associated with higher performance on both memory and executive function domains. Higher scores in role limitation due to physical problems, role limitation due to emotional problems, and general mental health subscales were associated with reduced risk of incident dementia. Higher MCS, but not PCS, predicted a reduced incident of all-cause dementia and AD. CONCLUSIONS: These findings suggest that diminution of HRQoL precedes the onset of diagnosable dementia and may be useful in the prediction of dementia onset.

Neuropsychological Function Response to Nocturnal Blue Light Blockage in Individuals With Symptoms of Insomnia: A Pilot Randomized Controlled Study.

OBJECTIVES: Insomnia is associated with neuropsychological dysfunction. Evidence points to the role of nocturnal light exposure in disrupted sleep patterns, particularly blue light emitted through smartphones and computers used before bedtime. This study aimed to test whether blocking nocturnal blue light improves neuropsychological function in individuals with insomnia symptoms. METHODS: This study used a randomized, placebo-controlled crossover design. Participants were randomly assigned to a 1-week intervention with amber lenses worn in wrap-around frames (to block blue light) or a 1-week intervention with clear lenses (control) and switched conditions after a 4-week washout period. Neuropsychological function was evaluated with tests from the NIH Toolbox Cognition Battery at three time points: (1) baseline (BL), (2) following the amber lenses intervention, and (3) following the clear lenses intervention. Within-subjects general linear models contrasted neuropsychological test performance following the amber lenses and clear lenses conditions with BL performance. RESULTS: Fourteen participants (mean(standard deviation, SD): age = 46.5(11.4)) with symptoms of insomnia completed the protocol. Compared with BL, individuals performed better on the List Sorting Working Memory task after the amber lenses intervention, but similarly after the clear lenses intervention (F = 5.16; p = .014; η2 = 0.301). A similar pattern emerged on the Pattern Comparison Processing Speed test (F = 7.65; p = 0.002; η2 = 0.370). Consideration of intellectual ability indicated that treatment with amber lenses "normalized" performance on each test from approximately 1 SD below expected performance to expected performance. CONCLUSIONS: Using a randomized, placebo-controlled crossover design, we demonstrated improvement in processing speed and working memory with a nocturnal blue light blocking intervention among individuals with insomnia symptoms. (JINS, 2019, 25, 668-677).

Depressive Symptoms Predict Incident Dementia in a Community Sample of Older Adults: Results From the Einstein Aging Study.

BACKGROUND:: There is increasing evidence that depressive symptoms are associated with increased risk of cognitive impairment and dementia in older adults. In current study, we aimed to investigate the effect of depressive symptoms on incident Alzheimer disease and all-cause dementia in a community sample of older adults. METHODS:: Participants were 1219 older adults from the Einstein Aging Study, a longitudinal cohort study of community-dwelling older adults in Bronx County, New York. The Geriatric Depression Scale (GDS, 15-item) was used as a measure of depressive symptoms. The primary outcome was incident dementia diagnosed using the Diagnostic and Statistical Manual, Fourth Edition, criteria. Cox proportional hazard models were used to estimate the risk of incident dementia as a function of GDS score for the whole population and also for 2 different time intervals, <3 years and ≥3 years after baseline assessment. RESULTS:: Among participants, 132 individuals developed dementia over an average 4.5 years (standard deviation [SD] = 3.5) of follow-up. Participants had an average age of 78.3 (SD = 5.4) at baseline, and 62% were women. Among all participants, after controlling for demographic variables and medical comorbidities, a 1-point increase in GDS was associated with higher incidence of dementia (hazard ratio [HR] = 1.11, P = .007). After up to 3 years of follow-up, depressive symptoms were not significantly associated with dementia incidence (HR = 1.09; P = .070). However, after more than 3 years, GDS score was a significant predictor of incident dementia (HR = 1.13, P = .028). CONCLUSIONS:: Our results suggest that depressive symptoms are associated with an increased risk of incident dementia in older adults.

Sleep and subjective cognitive decline in cognitively healthy elderly: Results from two cohorts.

Subjective cognitive decline may reflect a dementia prodrome or modifiable risk factor such as sleep disturbance. What is the association between sleep and subjective cognitive decline? Cross-sectional design, from two studies of older adults: the WHICAP in the USA and the HELIAD in Greece. A total of 1,576 WHICAP and 1,456 HELIAD participants, without mild cognitive impairment, dementia or severe depression/anxiety, were included. Participants were mostly women, with 12 (WHICAP) and 8 (HELIAD) mean years of education. Sleep problems were estimated using the Sleep Scale from the Medical Outcomes Study. Subjective cognitive decline was assessed using a structured complaint questionnaire that queries for subjective memory and other cognitive symptoms. Multinomial or logistic regression models were used to examine whether sleep problems were associated with complaints about general cognition, memory, naming, orientation and calculations. Age, sex, education, sleep medication, use of medications affecting cognition, co-morbidities, depression and anxiety were used as co-variates. Objective cognition was also estimated by summarizing neuropsychological performance into composite z-scores. Sleep problems were associated with two or more complaints: WHICAP: ß = 1.93 (95% confidence interval: 1.59-2.34), p ≤ .0001; HELIAD: ß = 1.48 (95% confidence interval: 1.20-1.83), p ≤ .0001. Sleep problems were associated with complaints in all the cognitive subcategories, except orientation for the WHICAP. The associations were noted regardless of objective cognition. At any given level of objective cognition, sleep disturbance is accompanied by subjective cognitive impairment. The replicability in two ethnically, genetically and culturally different cohorts adds validity to our results. The results have implications for the correlates, and potential aetiology of subjective cognitive decline, which should be considered in the assessment and treatment of older adults with cognitive complaints.