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Objective: Leukocyte telomere length (LTL) is a widely hypothesized biomarker of biological aging. Persons with shorter LTL may have a greater likelihood of developing dementia. We investigate whether LTL is associated with cognitive function, differently for individuals without cognitive impairment versus individuals with dementia or incipient dementia., Method: Enrolled subjects belong to the Long Life Family Study (LLFS), a multi-generational cohort study, where enrollment was predicated upon exceptional family longevity. Included subjects had valid cognitive and telomere data at baseline. Exclusion criteria were age ≤ 60 years, outlying LTL, and missing sociodemographic/clinical information. Analyses were performed using linear regression with generalized estimating equations, adjusting for sex, age, education, country, generation, and lymphocyte percentage., Results: Older age and male gender were associated with shorter LTL, and LTL was significantly longer in family members than spouse controls (p < 0.005). LTL was not associated with working or episodic memory, semantic processing, and information processing speed for 1613 cognitively unimpaired individuals as well as 597 individuals with dementia or incipient dementia (p < 0.005), who scored significantly lower on all cognitive domains (p < 0.005)., Conclusions: Within this unique LLFS cohort, a group of families assembled on the basis of exceptional survival, LTL is unrelated to cognitive ability for individuals with and without cognitive impairment. LTL does not change in the context of degenerative disease for these individuals who are biologically younger than the general population.

Background: The Long Life Family Study (LLFS) enrolled families exhibiting exceptional longevity. The goal of this article was to determine the prevalence and predictors of remaining independent after 7 years in the oldest generation., Methods: We examined 7-year change in physical (free of activities of daily living difficulty), cognitive (Mini-Mental State Examination score ≥ 24), and overall independence (physically/cognitively independent) in adults aged 90.3 ± 6.3 from LLFS's oldest generation. Potential predictors (n = 28) of remaining independent included demographics, diseases, biomarkers, anthropometrics, and physical and cognitive performance tasks and were determined using generalized estimating equations (α: p < .05). This was a discovery/exploratory analysis, so no multiple testing correction was employed and the results require independent replication., Results: At baseline (n = 1442), 67.3%, 83.8%, and 79.7% were overall, physically, and cognitively independent, respectively. After 7 years, 66% died, 7.5% were lost to follow-up, and the prevalence of overall independence decreased to 59.1% in survivors (-8.2%, 95% confidence interval: -14.1%, 2.2%). Of those with baseline independence, 156/226 (69.0%) remained independent. Predictors of remaining physically independent included younger age, better Short Physical Performance Battery score and lung function, smaller waist circumference, and lower soluble receptor for advanced glycation end-product levels (p < .05). Predictors of remaining cognitively independent included no cancer history, better Digit Symbol Substitution Test performance, and higher body weight (p < .05)., Conclusions: The prevalence of independence decreased by only 8.2% after 7 years, demonstrating the close correspondence between disability and mortality. Further, despite a mean baseline age of 90 years, a large proportion of survivors remained independent, suggesting this exceptional subgroup may harbor protective mechanisms., (© The Author(s) 2019. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: Patients with essential tremor exhibit heterogeneous cognitive functioning. Although the majority of patients fall under the broad classification of cognitively "normal," essential tremor is associated with increased risk for mild cognitive impairment and dementia. It is possible that patterns of cognitive performance within the wide range of normal functioning have predictive utility for mild cognitive impairment or dementia. These cross-sectional analyses sought to determine whether cognitive patterns, or "clusters," could be identified among individuals with essential tremor diagnosed as cognitively normal. We also determined whether such clusters, if identified, were associated with demographic or clinical characteristics of patients., Methods: Elderly subjects with essential tremor (age >55 years) underwent comprehensive neuropsychological testing. Domain means (memory, executive function, attention, visuospatial abilities, and language) from 148 individuals diagnosed as cognitively normal were partitioned using k-means cluster analysis. Individuals in each cluster were compared according to cognitive functioning (domain means and test scores), demographic factors, and clinical variables., Results: There were three clusters. Cluster 1 (n = 64) was characterized by comparatively low memory scores (p < .001), Cluster 2 (n = 39) had relatively low attention and visuospatial scores (p < .001), and Cluster 3 (n = 45) exhibited consistently high performance across all domains. Cluster 1 had lower Montreal Cognitive Assessment scores and reported more prescription medication use and lower balance confidence., Conclusions: Three patterns of cognitive functioning within the normal range were evident and tracked with certain clinical features. Future work will examine the extent to which such patterns predict conversion to mild cognitive impairment and/or dementia.

Cognitive impairment (CI) in older adults is frequently accompanied by difficulty performing complex everyday activities (e.g., managing finances). However, it is unclear if and how older adults with CI modify their activities (i.e., Do individuals continue, monitor, seek help with, change their approach to, or stop different activities?). In the current study, we examined if older adults with CI are concerned about their ability to carry out complex activities, if and how they modify activities based on their concern, and the factors associated with activity modification. We hypothesized that older adults with CI will more frequently be concerned about, and modify, everyday activities than cognitively healthy (HE) older adults, and that higher awareness of memory loss in the CI group would relate to more frequent modification. The sample included 81 older adults (51 HEs; mean age 70.02 (7.34) and 30 CI; mean age 75.97 (8.12)). Compared to HEs, the CI group reported having more concern about, F(3,77) = 5.50, p = 0.02, and modifying a greater number of activities, F(3,77) = 5.02, p = 0.03. Medication management (30%) and completing taxes (33.3%) were among the most frequently modified activities for the CI and HE groups, respectively. In the CI group, higher memory awareness was associated with more concern (r = .53, p = .005) and activity modification (r = 0.55, p = .003). Findings provide novel information about how cognitively diverse older adults navigate complex activities in daily life. We propose a preliminary theoretical model by which self-awareness may influence navigation of everyday activities in the context of CI., Competing Interests: The authors have declared that no competing interests exist.

Background: We previously demonstrated familial aggregation of memory performance within the Long Life Family Study (LLFS), suggesting that exceptional cognition (EC) may contribute to their exceptional longevity. Here, we investigated whether LLFS families with EC may also exhibit more favorable profiles of other age-related biomarkers., Methods: Nondemented offspring of the LLFS probands scoring 1.5 SD above the mean in a cognitive phenotype were classified as participants with EC. Families were categorized into EC (n = 28) and non-EC families (n = 433) based on having at least two EC offspring. Adjusted general estimating equations were used to investigate whether EC families had a better longevity and age-related biomarker profiles than non-EC families., Results: EC families exhibited higher scores on familial longevity than non-EC families (average Family Longevity Selection Score of 12 ± 7 vs 9 ± 8, p = 2.5 × 10-14). EC families showed a better a metabolic profile (β = -0.63, SE = 0.23, p = .006) than non-EC families. The healthier metabolic profile is related to obesity in an age-dependent fashion. The prevalence of obesity in EC families is significantly lower compared with non-EC families (38% vs 51%, p = .015) among family members less than 80 years of age; however, among EC family members 80 years of age and older, the prevalence of obesity is higher (40% vs 38%, p = .011). EC families also showed better physical/pulmonary function than non-EC families (β = 0.51, SE = 0.25, p = .042)., Conclusions: Long-live families with EC are characterized by a healthier metabolic profile which is related to the prevalence of obesity in the older family members. Our results suggest that familial exceptional longevity may be achieved through heterogeneous yet correlated pathways., (© The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Physical inactivity may be the result of medical comorbidities. Inactivity itself may also lead to important health consequences, especially in older patients. Essential tremor (ET) patients may have a variety of physical and cognitive problems that could detrimentally impact on level of physical activity. Yet, to our knowledge, there have been no studies of physical activity in these patients., Methods: Self-reported physical activity was assessed using the Physical Activity Scale for the Elderly (PASE) in 100 ET cases (mean age 80.5years) enrolled in a clinical study. Additional clinical measures were the total tremor score, Montreal Cognitive Assessment (MOCA) score and number of steps taken off of the straight line during tandem gait (a measure of balance)., Results: Lower PASE score was associated with older age, more tandem gait difficulty, higher total tremor score and lower MOCA score (all p<0.05). In a linear regression model that included total tremor score, MOCA score, number of steps off of the straight line during tandem gait, and age, higher total tremor score (p=0.046) and more steps off of the straight line during tandem gait (p=0.014) were independently associated with reductions in physical activity., Conclusions: Several of the motor features of ET (tremor and imbalance) are independently associated with reductions in level of physical activity., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The authors investigated whether cognitive function may be used as an endophenotype for longevity by assessing the cognitive performance of a family-based cohort consisting of 1380 individuals from 283 families recruited for exceptional survival in field centers in Boston, New York, Pittsburgh, and Denmark. Cognitive performance was assessed in the combined offspring of the Long Life Family Study (LLFS) probands and their LLFS siblings as compared with their spouses' cognitive performance. Our results indicate that the combined offspring of the LLFS probands and their siblings achieve significantly higher scores on both digit forward and backward tasks (p = 5 10(-5) and p = 8 10(-4) respectively) as well as on a verbal fluency task (p = 0.008) when compared with their spouse controls. No differences between groups were found for the other cognitive tests assessed. We conclude that LLFS family members in the offspring generation demonstrate significantly better performance on multiple tasks requiring attention, working memory, and semantic processing when compared with individuals without a family history of exceptional survival, suggesting that cognitive performance may serve as an important endophenotype for longevity., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: Metacognitive methodologies are used to examine the integrity of self-referential processing in healthy adults and have been implemented to study disorders of the self-concept in neurologic and psychiatric populations. However, the extent to which metacognitive evaluations assess a uniquely self-evaluative capacity that cannot be explained fully by primary cognitive functions, demographics, or mood is not clear. The objective of the current study was to examine whether metamemory and a metacognitive test of agency shared a self-referential association that would not be explained by cognition, demographics, or mood., Method: Thirty-eight nondemented older adults (Mini Mental State Examination [MMSE] ≥24 and mean age = 68.13) participated in metacognitive testing and completed cognitive testing and mood questionnaires. Bivariate correlations were used to evaluate the association between metamemory and agency, and to determine the cognitive (memory, attention, and executive functioning), demographic (age and education), and mood (anxiety and depression) correlates of each. Correlates of metamemory and agency were then entered into linear regression models to determine whether any association between metacognitive measures remained., Results: Metamemory was associated with agency judgments (n = 27), specifically those on self-controlled rather than computer-controlled trials (r = .41, p = .03). Regression results supported a role for agency in predicting metamemory, above and beyond memory and education (β = .39, p = .034). Metamemory was also an independent predictor of agency judgments (β = .36, p = .049)., Conclusions: The interrelation between metamemory and agency judgments suggests that metacognitive testing captures an important aspect of self-referential processing not otherwise assessed in a standard cognitive evaluation and may provide unique information about self-evaluative capacities in clinical populations., (PsycINFO Database Record (c) 2011 APA, all rights reserved.)

The ability to engage in self-reflective processes is a capacity that may be disrupted after neurological compromise; research to date has demonstrated that patients with traumatic brain injury (TBI) show reduced awareness of their deficits and functional ability compared to caretaker or clinician reports. Assessment of awareness of deficit, however, has been limited by the use of subjective measures (without comparison to actual performance) that are susceptible to report bias. This study used concurrent measurements from cognitive testing and confidence judgments about performance to investigate in-the-moment metacognitive experiences after moderate and severe traumatic brain injury. Deficits in metacognitive accuracy were found in adults with TBI for some but not all indices, suggesting that metacognition may not be a unitary construct. Findings also revealed that not all indices of executive functioning reliably predict metacognitive ability.

Background: High rates of leisure activity have been associated with reduced risk of Alzheimer disease (AD)., Objective: To determine whether prediagnosis leisure activity modifies the rate of cognitive decline in patients with AD., Design: Inception cohort followed up longitudinally for a mean of 5.3 years (up to 13.9 years)., Setting: Urban community., Participants: A total of 283 patients with incident AD (mean age, 79 years; 56.2% Hispanic and 31.1% African American)., Main Outcome Measures: Change in a composite cognitive score from diagnosis on and during the entire study follow-up., Results: In multivariate-adjusted generalized estimating equation models of postdiagnosis change (n = 133), each leisure activity was associated with an additional yearly decline of 0.005 of a z-score unit in cognitive score (P = .17). In models expanded to include cognitive change during study follow-up, including evaluations before and after diagnosis (n = 283), each activity was associated with an additional yearly decline of 0.005 of a z-score unit in cognitive score (P = .03). The association was strongest for intellectual activities., Conclusions: Greater participation in prediagnosis leisure activities, especially intellectual activities, was associated with faster cognitive decline, supporting the hypothesis that the disease course in AD may vary as a function of cognitive reserve.

Although executive dysfunction is the characteristic cognitive marker of behavioral variant frontotemporal dementia (bvFTD), episodic memory deficits are relatively common, and may be present even during the prodromal disease phase. In a cohort of mutation carriers with mild behavioral and/or cognitive symptoms consistent with prodromal bvFTD, we aimed to investigate patterns of performance on an abbreviated list learning task, with a particular focus on recognition memory. We further aimed to characterize the cognitive prodromes associated with the three major genetic causes of frontotemporal dementia, as emerging evidence suggests there may be subtle differences in cognitive profiles among carriers of different genetic mutations. Participants included 57 carriers of a pathogenic mutation in microtubule-associated protein tau (MAPT, N = 23), or progranulin (GRN, N = 15), or a or a hexanucleotide repeat expansion in chromosome 9 open reading frame 72 (C9orf72, N = 19), with mild cognitive and/or behavioral symptoms consistent with prodromal bvFTD. Familial non-carriers were included as controls (N = 143). All participants completed a comprehensive neuropsychological examination, including an abbreviated list learning test assessing episodic memory recall and recognition. MAPT mutation carriers performed worse than non-carriers in terms of list recall, and had difficulty discriminating targets from distractors on the recognition memory task, primarily due to the endorsement of distractors as targets. MAPT mutation carriers also showed nonverbal episodic memory and semantic memory dysfunction (object naming). GRN mutation carriers were variable in performance and overall the most dysexecutive. Slowed psychomotor speed was evident in C9orf72 repeat expansion carriers. Identifying the earliest cognitive indicators of bvFTD is of critical clinical and research importance. List learning may be a sensitive cognitive marker for incipient dementia in MAPT and potentially a subset of GRN carriers. Our results highlight that distinct cognitive profiles may be evident in carriers of the three disease-causing genes during the prodromal disease stage.

Introduction: A rapid and reliable neuropsychological protocol is essential for the efficient assessment of neurocognitive constructs related to emergent neurodegenerative diseases. We developed an AI-assisted, digitally administered/scored neuropsychological protocol that can be remotely administered in -10min. This protocol assesses the requisite neurocognitive constructs associated with emergent neurodegenerative illnesses. Methods: The protocol was administered to 77 ambulatory care/memory clinic patients (56.40% women; 88.50% Caucasian). The protocol includes a 6-word version of the Philadelphia (repeatable) Verbal Learning Test [P(r)VLT], three trials of 5 digits backward fromthe Backwards Digit Span Test (BDST), and the "animal" fluency test. The protocol provides a comprehensive set of traditional "core" measures that are typically obtained through paper-and-pencil tests (i.e., serial list learning, immediate and delayed free recall, recognition hits, percent correct serial order backward digit span, and "animal" fluency output). Additionally, the protocol includes variables that quantify errors and detail the processes used in administering the tests. It also features two separate, norm-referenced summary scores specifically designed to measure executive control and memory. Results: Using four core measures, we used cluster analysis to classify participants into four groups: cognitively unimpaired (CU; n = 23), amnesticmild cognitive impairment (MCI; n = 17), dysexecutive MCI (n = 23), and dementia (n = 14). Subsequent analyses of error and process variables operationally defined key features of amnesia (i.e., rapid forgetting, extra-list intrusions, profligate responding to recognition foils); key features underlying reduced executive abilities (i.e., BDST items and dysexecutive errors); and the strength of the semantic association between successive responses on the "animal" fluency test. Executive and memory index scores effectively distinguished between all four groups. There was over 90% agreement between how cluster analysis of digitally obtained measures classified patients compared to classification using a traditional comprehensive neuropsychological protocol. The correlations between digitally obtained outcome variables and analogous paper/pencil measures were robust. Discussion: The digitally administered protocol demonstrated a capacity to identify patterns of impaired performance and classification similar to those observed with standard paper/pencil neuropsychological tests. The inclusion of both core measures and detailed error/process variables suggests that this protocol can detect subtle, nuanced signs of early emergent neurodegenerative illness efficiently and comprehensively. [ABSTRACT FROM AUTHOR]

Background: Cognitive impairment is a feature of essential tremor (ET). There are no studies of the genetic drivers of this association. We examined whether the microtubuleassociated protein tau (MAPT) H1 haplotype is associated with cognitive performance in ET. Methods: ET cases genotyped for the MAPT H1 and H2 haplotypes completed a battery of neuropsychological tests at baseline and four follow-up evaluations. Chi-square, t-tests, and analyses of covariance examined associations between the presence of the MAPT H1 haplotype, cognitive diagnoses of normal, mild cognitive impairment (MCI), and dementia, and performance in specific cognitive domains. Results: We observed no evidence of cognitive differences as a function of the presence of the MAPT H1 haplotype. Specifically, cases with (n = 57) and without (n = 42) this haplotype did not differ with respect to the prevalence of diagnoses of MCI or dementia, p = 0.87. Moreover, cases with vs without this haplotype did not differ in either the age or point in the disease course at which observed conversions to MCI or dementia occurred, p's = 0.51. Finally, no haplotype-related differences were observed in performance in the cognitive domains of attention, executive function, language, memory, visuospatial or global ability, p's = 0.21, or in changes in performance in these domains across time, p's = 0.08. Discussion: The study in an ET cohort revealed no influence of MAPT haplotypes on cognitive performance. This study serves as a valuable foundation for future studies to expand our understanding of the genetic drivers of cognitive impairment in ET. Highlights This study found no evidence of cognitive differences between individuals with and without the MAPT H1 haplotype. Our work provides a valuable foundation for future work to expand our knowledge of the genetic drivers of cognitive impairment in ET. [ABSTRACT FROM AUTHOR]

Background: Impaired awareness of ability is common in dementia and has important clinical implications. Evidence from different clinical groups has shown that awareness can vary according to whether evaluation refers to self or other performance.Objective: The present study aimed to investigate awareness for self- and other-performance in Alzheimer's disease (AD) patients, exploring if results vary according to cognitive domain of the tasks. It was hypothesized that, particularly for memory tasks, AD patients would be inaccurate in relation to self-but not other-performance.Methods: Twenty-two mild to moderate AD patients and twenty-two healthy older adults participated. Two tasks, with reaction time and working memory tasks, were carried out, and each had a success and a failure condition. Participants were asked to estimate their own performance, as well as the performance of another person they observed. Awareness of performance was measured comparing participant estimations of performance with actual performance.Results: For both the reaction time and working memory tasks, results indicate that participants from both groups overestimated the performance in the failure condition and underestimated the performance in the success condition. They tended to overestimate more the performance of the other person compared to themselves. Additionally, for the working memory task, AD patients tended to overestimate more performances compared to controls.Conclusion: Findings suggest that the AD and control groups present the same pattern, with attribution of better performance to another person. For the AD group, the pattern of response was different for memory tasks, which may suggest domain-specific limited awareness. [ABSTRACT FROM AUTHOR]

Objective: Amyotrophic lateral sclerosis (ALS) is a multi-system disorder characterized primarily by motor neuron degeneration, but may be accompanied by cognitive dysfunction. Statistically appropriate criteria for establishing cognitive impairment (CI) in ALS are lacking. We evaluate quantile regression (QR), that accounts for age and education, relative to a traditional two standard deviation (SD) cutoff for defining CI. Methods: QR of cross-sectional data from a multi-center North American Control (NAC) cohort of 269 healthy adults was used to model the 5th percentile of cognitive scores on the Edinburgh Cognitive and Behavioral ALS Screen (ECAS). The QR approach was compared to traditional two SD cutoff approach using the same NAC cohort (2SD-NAC) and to existing UK-based normative data derived using the 2SD approach (2SD-UK) to assess the impact of cohort selection and statistical model in identifying CI in 182 ALS patients. Results: QR-NAC models revealed that age and education impact cognitive performance on the ECAS. Based on QR-NAC normative cutoffs, the frequency of CI in the 182 PENN ALS patients was 15.9% for ALS specific, 12.6% for ALS nonspecific, and 15.4% for ECAS total. This frequency of CI is substantially more conservative in comparison to the 2SD-UK (20.3%–34.6%) and modestly more conservative to the 2SD-NAC (14.3%–16.5%) approaches for estimating CI. Conclusions: The choice of normative cohort has a substantial impact and choice of statistical method a modest impact on defining CI in ALS. This report establishes normative ECAS thresholds to identify whether ALS patients in the North American population have CI. [ABSTRACT FROM AUTHOR]

Introduction: Cross-sectional analyses have associated familial longevity with better cognitive function and lower risk of cognitive impairment in comparison with individuals without familial longevity. The extent to which long-lived families also demonstrate slower rates of cognitive aging (i.e., change in cognition over time) is unknown. This study examined longitudinally collected data among 2 generations of the Long Life Family Study (LLFS) to compare rates of cognitive change across relatives and spouse controls. Methods: We analyzed change in 6 neuropsychological test scores collected approximately 8 years apart among LLFS family members (n = 3,972) versus spouse controls (n = 1,092) using a Bayesian hierarchical model that included age, years of follow-up, sex, education, generation, and field center and all possible pairwise interactions. Results: At a mean age of 88 years at enrollment in the older generation and 60 years in the younger generation, LLFS family members performed better than their spouses on the Digit Symbol Substitution Test (DSST) and the Logical Memory test. At follow-up, family members in the younger generation also showed slower decline than spouses on the DSST, whereas rates of change of Digit Span, fluency, and memory were similar between the 2 groups. Discussion/Conclusion: Individuals in families with longevity appear to have better cognitive performance than their spouses for cognitive processes including psychomotor processing, episodic memory, and retrieval. Additionally, they demonstrate longer cognitive health spans with a slower decline on a multifactorial test of processing speed, a task requiring the integration of processes including organized visual search, working and incidental memory, and graphomotor ability. Long-lived families may be a valuable cohort for studying resilience to cognitive aging. [ABSTRACT FROM AUTHOR]

Objective: Historically, psychiatric conditions and neurodegenerative diseases have been considered differential diagnoses in older adults with cognitive impairment. However, recent evidence has shown that neuropsychiatric symptoms may be prodromal for neurodegenerative disease. Subjective Cognitive Decline (SCD) is a potential marker for pre-clinical Alzheimer's Disease (AD) that is frequently related to mood disturbances. Delineating the relationship between neuropsychiatric symptoms, SCD, and cognitive impairment will help to define both the independent and combined utility of SCD and neuropsychiatric symptoms as markers of preclinical AD. This abstract uses the DSM-5 Cross-Cutting Measure (DSM-5 CC), a novel comprehensive screening tool for psychiatric symptoms, to examine the relationship between objective and subjective measures of cognition as they relate to neuropsychiatric symptoms. Participants and Methods: 27 community dwelling, cognitively diverse older adults (78% female, mean age 71.9 ± 7) were enrolled in the Concerns about Memory Problems (CAMP) study. Inclusion criteria included the expressed concern about memory functioning by participants on a 5-item screener, while exclusion criteria were defined as previous diagnosis of neurodegenerative diseases and/or major stroke. All participants completed neuropsychological testing and study surveys including the DSM-5 CC. Participants completed Level 1 and all Level 2 (L2) forms of the DSM-5 CC. Spearman two-tailed non-parametric correlations and independent samples t-tests were conducted to examine the relationship between the DSM-5 CC and the 5-item subjective cognition screener, as well as the DSM-5 CC and objective cognition results. Results: Subjective measures of cognition, as measured by answers to the 5-item screening measure, were significantly associated with DSM-5 CC measures. Question 1 on the SCD screener which asks, "Compared to others your age, do you have difficulty with memory or thinking abilities?" was associated with anger (p=.033) and depression (p=.018) L2 forms. Question 3, "Do any difficulties with memory or thinking abilities make it difficult for you to do things in daily life?)" was associated with the L2 forms for somatic symptoms (p=.016) and repetitive thoughts and behaviors (p<.001). Objective measures of cognition from neuropsychological testing also correlated with DSM-5 CC sub-scores. Digits Backwards Length (DBL) correlated with DSM-5 CC Level 1 Sum (r= -.57, p=.002). DBL (r=-.59 p=.001) and Digits Backwards Total Correct (DBTC) (r=-.47, p=.013) associated with somatic symptoms L2 and sleep L2 (DBL: r=,-.45 p=.019; DBTC: r=-.39, p=.044). Category Naming (animals) was also associated with anxiety L2 (r=-.42, p=.030). Conclusions: Subjective and objective measures of cognition were each related to sub-scores of the DSM-5 CC. Interestingly, the associations were largely non-overlapping. These results highlight the importance of considering a wide range of neuropsychiatric symptoms in the assessment of SCD and cognitive impairment. Findings contribute to the growing body of literature suggesting that neuropsychiatric symptoms should be studied in conjunction with cognitive symptoms among older adults as co-occurring phenomena. Future directions will need to include longitudinal studies that can examine the prodromal nature of SCD and neuropsychiatric symptoms for Alzheimer's and other neurodegenerative disorders. [ABSTRACT FROM AUTHOR]

To assess the predictive value of neuropsychological tests for severe dependency in Alzheimer's disease as defined by the Equivalent Institutional Care Rating Scale, in a multiethnic, community cohort. The sample included 146 elders from the Predictors 3 cohort. Cox proportional hazard models tested the predictive value of each neuropsychological test at baseline on relative risk of meeting severe dependency. Higher semantic processing and memory test scores at baseline were associated with lower risk of meeting severe dependency in the adjusted Cox models. The integrity of semantic processing and memory abilities in dementia appears to predict time to severe functional dependency. [ABSTRACT FROM AUTHOR]

Objectives: Myocyte Enhancer Factor 2C (MEF2C) is identified as a candidate gene contributing to the risk of developing Alzheimer’s disease. However, little is known about whether MEF2C plays a role in specific aspects of cognition among older adults. The current study investigated the association of common variants in the MEF2C gene with four cognitive domains including memory, visuospatial functioning, processing speed and language among non-demented individuals. Method: Participants from two ethnic groups, Non-Hispanic White (NHW; n = 537) and Caribbean Hispanic (CH; n = 1,197) from the Washington Heights-Inwood Community Aging Project (WHICAP) study, were included. Genetic association analyses using WHICAP imputed genome-wide data (GWAS) were conducted for the various cognition domains. Results: Single nucleotide polymorphisms (SNP) variants in the MEF2C gene showed nominally significant associations in all cognitive domains but for different SNPs across both the ethnic groups. In NHW participants, the strongest associations were present for memory (rs302484), language (rs619584), processing speed (rs13159808), and visuospatial functioning (several SNPs). In CH, strongest associations were observed for memory (rs34822815), processing speed (rs304141), visuospatial functioning (rs10066711 and rs10038371), and language (rs304153). Discussion: MEF2C variant-cognitive associations shed light on an apparent role for MEF2C in both memory and non-memory aspects of cognition in individuals from NHW and CH ancestries. However, the little overlap in the specific SNP-cognition associations in CH versus NHW highlights the differences in genetic architectural variations among those from different ancestries that should be considered while studying the MEF2C gene. [ABSTRACT FROM AUTHOR]

Background: The utility of subjective cognitive decline (SCD) as an indicator of preclinical AD is overshadowed by its inconsistent association with objective cognition.Objective: This study examines if manipulations of SCD measurement affect its association with early cognitive dysfunction characteristic of preclinical AD.Methods: Cognitively healthy older adults (n = 110) completed SCD questionnaires that elicited complaints in general, compared to 5 years ago (retrospective SCD) and compared to their peers (age-anchored SCD) in binary and Likert scales. Outcome cognitive tasks included an associative memory task (Face-Name Test), a visual short-term memory binding task (STMB test), and a clinical neuropsychological list learning test (Selective Reminder Test).Results: SCD complaints, when compared to age-matched peers (age-anchored SCD) were endorsed less frequently than complaints compared to 5 years ago (retrospective SCD) (p < 0.01). In demographically adjusted regressions, age-anchored ordinal-rated SCD was associated with short term memory binding (β= -0.22, p = 0.040, CI = -0.45, -0.01), associative memory (β= -0.26, p = 0.018, CI = -0.45, -0.06), and list learning (β= -0.31, p = 0.002, CI = -0.51, -0.12). Retrospective and general ordinal-rated SCD was associated with associative memory (β= -0.25, p = 0.012, CI = -0.44, -0.06; β= -0.29, p = 0.003, CI = -0.47, -0.10) and list learning only (β= -0.25, p = 0.014, CI = -0.45, -0.05; β= -0.28, p = 0.004, CI = -0.48, -0.09).Conclusion: Ordinal age-anchored SCD appears better suited than other SCD measurements to detect early cognitive dysfunction characteristic of preclinical AD. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to examine whether reduced awareness of memory deficits in individuals with dementia is associated with more frequent need for Medicare home health care services.Methods: Cross-sectional analyses were conducted in a multicenter, clinic-based cohort. In total, 192 participants diagnosed with dementia and their informants were independently asked whether or not the participant demonstrated cognitive symptoms of dementia related to memory and word-finding. Participant self-awareness was measured as the discrepancy between participant and caregiver report of these symptoms. Annual Medicare home health benefit use data was obtained from Medicare claims matched by year to the Predictors study visit.Results: Participants that used home health services had lower awareness scores than those who did not. Awareness remained independently associated with home health use in a logistic regression adjusted for age, gender, education, caregiver relationship, global cognition, dementia subtype, and medical comorbidities.Implications: Reduced self-awareness of memory deficits in individuals with dementia is associated with more frequent use of Medicare home health services. The disproportionate use of in-home assistance as a function of awareness level may reflect dangers faced by patients, and challenges faced by caregivers, when patients have limited awareness of their memory deficits. Current results have implications for clinical care, caregiver education, and models of health care utilization. [ABSTRACT FROM AUTHOR]

Objectives: Essential tremor (ET) confers an increased risk for developing both amnestic and non-amnestic mild cognitive impairment (MCI). Yet, the optimal measures for detecting mild cognitive changes in individuals with this movement disorder have not been established. We sought to identify the cognitive domains and specific motor-free neuropsychological tests that are most sensitive to mild deficits in cognition as defined by a Clinical Dementia Rating (CDR) of 0.5, which is generally associated with a clinical diagnosis of MCI. Methods: A total of 196 ET subjects enrolled in a prospective, longitudinal, clinical-pathological study underwent an extensive motor-free neuropsychological test battery and were assigned a CDR score. Logistic regression analyses were performed to identify the neuropsychological tests which best identified individuals with CDR of 0.5 (mild deficits in cognition) versus 0 (normal cognition). Results: In regression models, we identified five tests in the domains of Memory and Executive Function which best discriminated subjects with CDR of 0.5 versus 0 (86.9% model classification accuracy). These tests were the California Verbal Learning Test II Total Recall, Logical Memory II, Verbal-Paired Associates I, Category Switching Fluency, and Color-Word Inhibition. Conclusions: Mild cognitive difficulty among ET subjects is best predicted by combined performance on five measures of memory and executive function. These results inform the nature of cognitive dysfunction in ET and the creation of a brief cognitive battery to assess patients with ET for cognitively driven dysfunction in life that could indicate the presence of MCI. (JINS , 2018, 24 , 1084–1098) [ABSTRACT FROM AUTHOR]

Background: Depressive symptoms are associated with essential tremor (ET). However, the relationship between cognitive, functional, and motor measures with depressive symptoms in ET is not yet understood.Methods: The following measures were cross-sectionally assessed in a group of 223 subjects with ET: the Montreal Cognitive Assessment (MoCA) Scale, the Lawton Independent Activities of Daily Living (IADL) Scale, a neurologist assessment of tremor severity, and the Geriatric Depression Scale (GDS).Results: 20% (44) of the subjects met GDS criteria for depression (GDS ≥ 10). 43% (94) of the subjects showed at least some cognitive impairment (≤24 on the MoCA), and 15.3% (34) reported significant functional impairment (IADL score < 7). There was no significant association between GDS score and tremor scale score. The total GDS was negatively associated with the total MoCA score (Spearman's r = -0.15, p = 0.03). The total GDS was also negatively associated with the IADL score (Spearman's r = -0.19, p = 0.02), (logistic model odds ratio, OR = 4.91, p < 0.01). Over 60% of subjects who were depressed, per GDS cut-off score (≥10), were not receiving medical treatment for depression.Conclusions: There was a high point prevalence of depressive symptoms in subjects with ET. Self-report depressive symptoms are dissociated from tremor severity. Hence, these data do not support the hypothesis that depression in ET represents a psychological reaction to the tremor. There appears to be a clustering of cognitive, functional, and depressive symptoms in ET. Screening of depression in ET can improve our understanding and treatment of this disorder. [ABSTRACT FROM AUTHOR]

Background: We previously demonstrated familial aggregation of memory performance within the Long Life Family Study (LLFS), suggesting that exceptional cognition (EC) may contribute to their exceptional longevity. Here, we investigated whether LLFS families with EC may also exhibit more favorable profiles of other age-related biomarkers.Methods: Nondemented offspring of the LLFS probands scoring 1.5 SD above the mean in a cognitive phenotype were classified as participants with EC. Families were categorized into EC (n = 28) and non-EC families (n = 433) based on having at least two EC offspring. Adjusted general estimating equations were used to investigate whether EC families had a better longevity and age-related biomarker profiles than non-EC families.Results: EC families exhibited higher scores on familial longevity than non-EC families (average Family Longevity Selection Score of 12 ± 7 vs 9 ± 8, p = 2.5 × 10-14). EC families showed a better a metabolic profile (β = -0.63, SE = 0.23, p = .006) than non-EC families. The healthier metabolic profile is related to obesity in an age-dependent fashion. The prevalence of obesity in EC families is significantly lower compared with non-EC families (38% vs 51%, p = .015) among family members less than 80 years of age; however, among EC family members 80 years of age and older, the prevalence of obesity is higher (40% vs 38%, p = .011). EC families also showed better physical/pulmonary function than non-EC families (β = 0.51, SE = 0.25, p = .042).Conclusions: Long-live families with EC are characterized by a healthier metabolic profile which is related to the prevalence of obesity in the older family members. Our results suggest that familial exceptional longevity may be achieved through heterogeneous yet correlated pathways. [ABSTRACT FROM AUTHOR]

Introduction: Informant report of symptoms is essential for diagnosing and characterizing Alzheimer disease (AD). Differences in the perception and experience of dementia across ethnicities may influence informant report. Understanding such differences is critical given that among those with AD, Hispanics are disproportionately affected.Methods: Cross-sectional analyses examined informant report of cognitive and functional symptoms in mild AD across white (n=107) and Caribbean Hispanic (n=71) informants. To explore its accuracy, informant report of symptoms was compared against objective measures of patient performance.Results: Adjusted analyses revealed Hispanics reported more symptoms than white informants. Informant report of symptoms was inversely correlated with patients' global cognition in both ethnic groups. Only Hispanic report of symptoms was significantly associated with memory and language performance.Discussion: Informant report of symptoms was associated with patients' global cognition, reflecting relatively accurate informant reports in both ethnic groups, and was stronger in Hispanics when examining memory and language. Such differences may reflect cultural caregiving practices and perceptions of dementia, having implications for diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Background: Essential tremor (ET) is associated with physical and cognitive impairments, as well as embarrassment, avoidance of social settings, and related difficulties that negatively impact the lives of patients. In similar disease contexts, burden on friends and relatives acting as caregivers has been noted and has well-documented implications. There has been no study examining caregiver burden related to ET. Methods: Data were gathered from 55 ET participants enrolled in a clinical study and their caregivers. The Zarit Burden Interview was used to assess caregiver burden. To assess clinical features that may be associated with burden, we collected several variables including the Montreal Cognitive Assessment, self-reported tremor disability, a videotaped neurological examination, questionnaires assessing ET participants' suffering, caregivers' perceptions of that suffering, and both caregiver and ET participant depressive symptoms. Spearman's correlations were performed between caregiver burden and clinical features, and we created a multivariate linear regression model predicting caregiver burden. results: Many ET caregivers provide little to no care and experience little to no burden. However, some caregivers (11%) provide over 25 h of care/week, and 13% experience high levels of burden. Caregivers most commonly provided assistance with writing and cooking. Increased burden was associated with the ET participants' decreased cognition, more caregiving tasks, more hours/week of caregiving activities, a longer duration of care, more ET participant falls/year, more medications taken by the ET participant, and more depressive symptoms in both the ET participant and the caregiver (all p < 0.05). ET participants' suffering and their caregivers' perceptions of suffering were both associated with increased burden. Neither tremor severity score nor self-reported tremor disability score was associated with increased caregiver burden. Using a multivariate linear regression model, we found that caregivers' increased perception of their partners' suffering was the best predictor of caregiver burden. Conclusion: While not all relatives and friends of ET patients provide extensive care or experience high burden, there is a group reporting high levels of caregiver burden that requires the attention and counseling of clinicians. This burden is associated with primarily non-tremor symptoms of ET and with caregivers' perception that their partners are suffering. [ABSTRACT FROM AUTHOR]

ObjectivesIndividuals with essential tremor (ET) exhibit a range of cognitive deficits generally conceptualized as “dysexecutive” or “fronto-subcortical,” and thought to reflect disrupted cortico-cerebellar networks. In light of emerging evidence that ET increases risk for Alzheimer’s disease (AD), it is critical to more closely examine the nature of specific cognitive deficits in ET, with particular attention to amnestic deficits that may signal early AD.MethodsWe performed a cross-sectional analysis of baseline data from 128 ET cases (age 80.4±9.5 years) enrolled in a longitudinal, clinical-pathological study. Cases underwent a comprehensive battery of motor-free neuropsychological tests and a functional assessment to inform clinical diagnoses of normal cognition (ET-NC), mild cognitive impairment (MCI) (ET-MCI), or dementia (ET-D). ET-MCI was subdivided into subtypes including: amnestic single-domain (a-MCI), amnestic multi-domain (a-MCI+), non-amnestic single-domain (na-MCI), or non-amnestic multi-domain (na-MCI+).ResultsNinety-one (71.1%) cases were ET-NC, 24 (18.8%) were ET-MCI, and 13 (10.2%) were ET-D. Within MCI, the a-MCI+ subtype was the most common (13/24; 54.2%) followed by a-MCI (4/24; 16.7%), na-MCI+ (4/24; 16.7%), and na-MCI (3/24; 12.5%). Cases with amnestic MCI demonstrated lower recognition memory Z-scores (−2.4±1.7) than non-amnestic groups (−0.9±1.2) (p=.042).ConclusionsAmnestic MCI, defined by impaired memory recall but associated with lower memory storage scores, was the most frequent MCI subtype in our study. Such impairment has not been explicitly discussed in the context of ET and may be an early hallmark of AD. Results have implications for the prognosis of specific cognitive deficits in ET. (JINS, 2017, 23, 390–399) [ABSTRACT FROM PUBLISHER]

Background: Essential tremor (ET) is not exclusively a tremor disorder; it is also associated with cognitive and gait dysfunction. However, a gap in knowledge is that the relationship between cognitive and gait dysfunction has not been studied in detail in ET. We examined the relationship between cognition and balance and falls in ET and hypothesized that cognitive dysfunction in ET patients would be associated with greater problems with balance and more falls. Methods: ET cases were recruited into the Clinical-pathological Study of Cognition in ET. A comprehensive cognitive assessment was performed. This included the Montreal Cognitive Assessment (MoCA) to measure global cognition, multiple motor-free tests comprehensively assessing performance in each cognitive domain, and an assignment of Clinical Dementia Rating (CDR) scores. We collected data on the number of reported falls in the past year, and balance confidence was assessed using the 6-item Activities of Balance Confidence Scale. These cross-sectional analyses utilized baseline data. Results: There were 199 ET cases (mean age 78.6 years). In linear regression models that considered the effects of numerous confounding variables, lower global cognition (poorer cognition) was associated with greater number of falls and reduced balance confidence (p < 0.05). In similar adjusted linear regression models, higher CDR score (poorer functional cognition) was associated with greater number of falls and reduced balance confidence (p < 0.05). We also assessed whether number of falls and balance confidence was associated with performance in specific cognitive domains. Number of falls was most closely linked with performance on tests of executive function, and balance confidence, with executive function, attention, and memory. Conclusion: These data indicate that a correlate of poorer cognition in ET is greater number of falls and lower balance confidence. Cognition should enter the dialog with ET patients as an issue of clinical significance. [ABSTRACT FROM AUTHOR]

Assessment of the earlier stages of Alzheimer's disease requires different strategies than those previously developed for fully syndromal Alzheimer's disease. This challenge is further magnified in very early stages, where symptomatology may be minimal and functional deficits very subtle to absent. This paper reviews strategies for performance-based assessment of the early stages of Alzheimer's disease, including assessments of cognition, functional capacity, and social cognition. Meetings with an International Society for CNS Clinical Trials and Methodology working group served as the basis for this paper and its companion. The current state of the art of detection and staging-oriented assessments is presented, and information is provided regarding the practicality and validity of these approaches, with a special focus on their usefulness in clinical trials for new medication development. [ABSTRACT FROM AUTHOR]

The extent to which social cognitive changes reflect a discrete constellation of symptoms dissociable from general cognitive changes in Alzheimer's disease (AD) is unclear. Moreover, whether social cognitive symptoms contribute to disease severity and progression is unknown. The current multicenter study investigated cross-sectional and longitudinal associations between social cognition measured with six items from the Blessed Dementia Rating Scale, general cognition, and dependence in 517 participants with probable AD. Participants were monitored every 6 months for 5.5 years. Results from multivariate latent growth curve models adjusted for sex, age, education, depression, and recruitment site revealed that social cognition and general cognition were unrelated cross-sectionally and throughout time. However, baseline levels of each were related independently to dependence, and change values of each were related independently to change in dependence. These findings highlight the separability of social and general cognition in AD. Results underscore the relevance of considering social cognition when modeling disease and estimating clinical outcomes related to patient disability. [ABSTRACT FROM AUTHOR]

Abstract: Research to understand variability at the highest end of the cognitive performance distribution has been scarce. Our aim was to define a cognitive endophenotype based on exceptional episodic memory (EM) performance and to investigate familial aggregation of EM in families from the Long Life Family Study (LLFS). Using a sample of 1911 nondemented offspring of long-lived probands, we created a quantitative phenotype, EM (memory z ≥ 1.5), and classified LLFS families as EM and non-EM families based on the number of EM offspring. We then assessed differences in memory performance between LLFS relatives in the parental generation of EM families and those in non-EM families using multivariate analysis adjusted for APOE Apolipoprotein E genotype. LLFS relatives in the proband generation from EM families showed better EM performance than those from non-EM families (β = 0.74, standard error = 0.19, p = 1.4 × 10−4). We demonstrated that there is a familial correlation of the EM endophenotype, suggesting that genetic variants might influence memory performance in long-lived families. [Copyright &y& Elsevier]

While essential tremor (ET) has traditionally been categorized as a pure motor disease, cross-sectional and longitudinal studies of cognition in ET have demonstrated that these patients may have cognitive dysfunction. Recent epidemiological studies demonstrate an association between ET (particularly with onset after age 65) and increased risk for cognitive impairment and dementia. Although existing studies have generally conceptualized cognitive changes in ET as consistent with a ‘frontosubcortical’ or ‘corticocerebellar’ profile, results from these same studies suggest that cognitive impairment in ET may in fact be heterogeneous. Furthermore, the underlying mechanisms remain uncertain. Cognitive changes could be a byproduct of the cerebellar dysfunction of ET itself; alternately, they may be a feature of concomitant neurodegenerative diseases that have been associated in several studies with ET, including Alzheimer’s disease, Parkinson’s disease or progressive supranuclear palsy. While the study of cognitive dysfunction in ET has received research attention in recent years, the results of these studies have not been translated into the clinical domain and clinical practice. This review first summarizes the current literature on the potential relationships between ET and cognitive change. We then suggest areas of further clinical evaluation and treatment; these suggestions are directed at physicians caring for ET patients who may demonstrate or complain of cognitive impairment. As we discuss, clinicians should ideally screen ET patients for possible signs or symptoms of cognitive impairment in addition to assessing for psychiatric comorbidity and quality of life. These recommendations are in contrast to most current clinical practice, which does not routinely include such assessment among ET patients. To our knowledge, there have been no pharmacotherapeutic trials to date of any agent for cognitive change associated with ET. We believe that studies for this indication are now called for. Future efforts in this direction will also need to take into account the pathobiology of cognitive changes in ET, which itself is an area that is ripe for future investigations. [ABSTRACT FROM PUBLISHER]

Frontotemporal dementia (FTD) represents a spectrum of non-Alzheimer's degenerative conditions associated with focal atrophy of the frontal and/or temporal lobes. Frontal and temporal regions of the brain have been shown to be strongly involved in executive function, social cognition and language processing and, thus, deficits in these domains are frequently seen in patients with FTD or may even be hallmarks of a specific FTD subtype (i.e. relatively selective and progressive language impairment in primary progressive aphasia). In this review we have attempted to delineate how language, executive function, and social cognition may contribute to the diagnosis of FTD syndromes, namely the behavioural variant FTD as well as the language variants of FTD including the three subtypes of primary progressive aphasia (PPA): non-fluent/agrammatic, semantic and logopenic. This review also addresses the extent to which deficits in these cognitive areas contribute to the differential diagnosis of FTD versus Alzheimer's disease (AD). Finally, early clinical determinants of pathology are briefly discussed and contemporary challenges to the diagnosis of FTD are presented. [ABSTRACT FROM AUTHOR]

Background: Clock drawing is part of the Montreal Cognitive Assessment (MoCA) test but may have administration and scoring limitations. We assessed (1) the reliability of the MoCA clock criteria relative to a published error scoring approach, (2) whether command-only administration could distinguish dementia from cognitively intact individuals and (3) the value of adding a clock copy condition to the MoCA. Methods: Three novice raters and clocks from dementia and control participants were used to assess the 3 aims. Results: MoCA interrater and intrarater reliability were low (i.e. intraclass correlation coefficient = 0.12-0.31) and required repeat training. Clocks drawn to command classified dementia at chance. Inclusion of a copy condition demonstrated expected dementia subgroup patterns. Conclusion: Reliable clock scoring with MoCA criteria requires practice. Supplementing a clock copy to the standard MoCA test (takes <1 min) will improve dementia assessment. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Memory awareness in early Alzheimer's disease (AD) influences capacity to provide informed consent for a memory treatment. This study investigated the extent to which aspects of memory awareness influence everyday decision-making capacity about medication management in AD. 42 participants with mild AD and 50 healthy elders underwent clinical ratings of memory awareness, metamemory testing, and an interview of everyday decision-making capacity regarding medication management. 45% of AD subjects were classified as aware (AAD) and 55% as unaware (UAD) based on clinical ratings and supported by metamemory testing (P = .015). Capacity was impaired in each of the AD groups as compared to the healthy elders F(2, 67) = 17.63, UAD, P < .01; AAD, P = .01). Within the AD group, capacity correlated selectively with awareness as measured with clinical ratings (r = -.41, P = .007) but not objective metamemory testing (r = -.10, P = .60). Appreciation scores were lower in UAD as compared with AAD F(1, 35) = 8.36, P = .007. Unawareness of memory loss should heighten clinicians' concern about everyday decision-making capacity in AD. [ABSTRACT FROM AUTHOR]

Introduction: Although the hallmark feature of essential tremor (ET) is tremor, there is growing appreciation that cognitive impairment also occurs, including increased prevalence of mild cognitive impairment (MCI) and increased prevalence and incidence of dementia. With emerging knowledge of ET-cognitive impairment, come fundamental questions regarding its course, bases, predictors and clinical outcomes. Studies in the general population and in Parkinson's disease (PD), a related movement disorder, offer a starting point from which to begin filling these clinically important knowledge gaps.Methods: A PubMed search (June 2018) identified articles for this review.Results: Much of our knowledge of cognitive impairment in ET is of the static condition (e.g., prevalence of cognitive impairment in ET), with nearly no information on its bases, predictors and dynamics (i.e., course, and clinical outcomes). In PD, where such data have been published, rates of cognitive decline and conversion to MCI/dementia are higher than in the general population. Predictors of cognitive change in PD and the general population have also been identified, yet they only partially overlap one another.Conclusion: The predictors and dynamics of cognitive impairment have been investigated fairly extensively in the general population, to a somewhat lesser extent in PD, and are emerging only now in ET. We suggest that longitudinal studies specific to ET are needed, and we outline variables to be considered in these investigations. Increased knowledge of ET-cognitive impairment will facilitate meaningful counseling of patients and their families. [ABSTRACT FROM AUTHOR]

Although essential tremor (ET) is associated with cognitive decline, we know little about how specific cognitive changes predict significant events in patients' lives. We examined the relations of attention, executive function, language, memory, and visuospatial performance to the occurrence of near falls, falls, walking aid use, home health aide use, non-independent living and hospitalizations within a prospective, longitudinal study of ET cases. We expected executive function and memory to be most strongly associated with these events. 131 ET cases (mean age at baseline = 76.4 ± 9.4 years; 109 normal cognition; 17 mild cognitive impairment, 5 demented) completed questionnaires (clinical history and occurrence of life events) and a battery of neuropsychological tests at baseline and at 18, 36, and 54 months. We assessed associations between cognitive functioning and outcomes via regression equations. Cases with lower baseline levels of executive function reported more near falls, p < 0.006, and were more likely to use a walking aid, p < 0.03, odds ratio (OR) = 2.89 during the follow-up period, than were other cases. Decline in executive function was associated with home health aide use during follow-up, p < 0.04, OR = 3.34. Baseline visuospatial performance also bore a marginally significant association with non-independent living arrangements during follow-up, p < 0.06, OR = 2.13. These effects were independent of age and tremor severity. These data establish the important role that cognitive decline, and executive function specifically, play in the experiences of ET patients. Moreover, these associations are of sufficient magnitude to have significant clinical implications. • Examined relations of life events to cognitive functioning in ET patients. • Examined events such as hospitalizations, changes in living arrangements, falls. • A prospective, longitudinal cohort of ET cases was evaluated across 4 time points. • Executive function most consistently associated with occurrence of these events. • These links are of sufficient magnitude to have important clinical implications. [ABSTRACT FROM AUTHOR]

Introduction: Essential tremor (ET), a common movement disorder, is characterized by motor, cognitive and psychiatric symptoms. Depressed mood, a symptom of ET, has historically been viewed as a psychological response to disability. However, depressive symptoms are emerging as a predictor of cognitive decline across several clinical populations. We examined if depressive symptoms predict decline in global cognition, memory, and executive functioning among older adults with ET.Methods: 125 cognitively normal participants with ET completed three in-person assessments of cognition, mood, and motor symptoms at baseline, 18 months, and 36 months; baseline data were collected from July 2014-July 2016. Depressive symptoms were measured with the Geriatric Depression Scale. Cognitive functioning was measured via a 3-4 hour neuropsychological evaluation. Generalized linear regression models examined depressive symptoms as a predictor of decline in global cognition, executive functioning (EF), and memory.Results: Participants were grouped according to a median split (GDS <5 versus ≥ 5) due to the bimodal distribution of the data. In unadjusted models, depressive symptoms did not predict change in global cognition (b = -0.002, p = .502) or EF (b = 0.000, p = .931), however individuals with GDS ≥ 5 demonstrated faster memory decline in unadjusted (b = -0.008, p = .039) and adjusted models (b = -0.009, p = .019).Conclusion: The presence of 5 or more depressive symptoms predicted mildly faster memory decline in cognitively normal older adults with ET over 36 months. We discuss potential mechanisms and clinical implications. [ABSTRACT FROM AUTHOR]

Background: In numerous case-control studies, essential tremor (ET) has been associated with cognitive impairment. ET is often familial. However, cognitive impairment has not been studied in family members of ET cases. Endophenotypes are measurable clinical characteristics that may be present in individuals with increased risk for disease; as such, they may be present before disease onset. We administered a global cognitive screen to first-degree relatives of ET cases (FD-ET) and age-matched controls (Co).Methods: We administered the Montreal Cognitive Assessment (MoCA) to 156 FD-ET and 73 Co, none of whom were diagnosed with ET or reported tremor. MoCA <26 was considered suggestive of cognitive impairment.Results: FD-ET and Co were similar with respect to age (60.1 ± 8.3 vs. 60.9 ± 7.4 years) and numerous demographic factors. FD-ET and Co also had similar MoCA scores; however, 34 of 156 (21.8%) FD-ET had a MoCA score <26 vs only 5 (6.9%) of 73 Co (p = 0.004). In a univariate logistic regression model, FD-ET were 3.79 times more likely to have a low (<26) MoCA than were Co (odds ratio = 3.79, p = 0.008). In a multivariate logistic regression model, adjusting for age and other covariates, FD-ET were 4.83 times more likely to have a low MoCA than were Co (odds ratio = 4.83, p = 0.003).Conclusion: More FD-ET had low MoCA scores when compared with Co. These data provide additional support for the scientific notions that (1) cognitive difficulties are a disease-associated feature of ET and (2) there may be a pre-tremor phase of illness in ET. [ABSTRACT FROM AUTHOR]

There is increasing evidence that essential tremor (ET) is a complex and heterogeneous disorder with nonmotor features including cognitive deficits and sleep problems. We are unaware of a study that has examined sleep deficits in ET across the full spectrum of cognitive presentations. Cross-sectional (baseline) data on self-reported nighttime sleep dysfunction and excessive daytime sleepiness were collected using the Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale (ESS) in 96 ET cases enrolled in a prospective study. Cases underwent a comprehensive neuropsychological assessment, and were classified as ET with normal cognition (ET-NC), ET with mild cognitive impairment (ET-MCI), and ET with dementia (ET-D). PSQI scores did not significantly differ across the three ET cognitive groups (p = 0.22). ESS scores were highest (more daytime sleepiness) in the ET-MCI group, followed by the ET-D and ET-NC groups, respectively (p = 0.016). We examined sleep dysfunction across the cognitive spectrum in ET. We demonstrate for the first time that excessive daytime sleepiness is greater in ET-MCI than ET-NC. Unpredicted low ESS scores in the dementia group raises two possibilities: a self-report bias related to cognitive impairment and/or the possibility that currently undefined pathological heterogeneity in ET may map onto multiple presentations of non-motor deficits. [ABSTRACT FROM AUTHOR]

Essential tremor (ET) is a clinically heterogeneous disease characterized by motor and non-motor features, including cognitive impairment. In a cross-sectional analysis, we determined whether the presence and severity of motor features of ET are associated with cognitive performance. Participants enrolled in a study that used motor and neuropsychological measures to characterize a cohort of ET subjects. Action tremor severity and additional motor features (rest tremor, intention tremor, cranial tremor, dystonia, tandem gait missteps) were assessed in non-demented participants. Participants completed a cognitive test protocol assessing domains of memory, executive function, attention, visuospatial ability, and language. An average z-score was calculated to represent global cognition. There were 204 ET participants (mean age 78.6, range 55–95). Participants with 10 missteps were more likely to have MCI than those with 0 or 1 misstep (p < 0.001). In unadjusted linear regression models, action tremor severity (p = 0.010), rest tremor (p < 0.001), and tandem gait missteps (p < 0.001) were negatively associated with global cognition. In adjusted models, only tandem gait missteps were negatively associated with global cognition (p < 0.001). Missteps were also negatively associated with memory (p < 0.001), executive function (p < 0.001), attention (p = 0.011), and visuospatial function (p = 0.043). No other motor features were associated with global cognition in adjusted models (p > 0.05). Among non-demented participants with ET, there is an association between cognitive performance and tandem gait missteps, but no other motor features of ET. This is a first step in establishing impaired tandem gait as a possible indicator of cognitive impairment in patients with ET. • More tandem gait missteps are associated with worse global cognition. • Other motor features of essential tremor are not associated with global cognition. • Participants with ten missteps are more likely to have cognitive impairment. [ABSTRACT FROM AUTHOR]