Search

IntroductionLate-onset Alzheimer's disease (LOAD) has a strong genetic component. Participants in Long-Life Family Study (LLFS) exhibit delayed onset of dementia, offering a unique opportunity to investigate LOAD genetics.MethodsWe conducted a whole genome sequence analysis of 3475 LLFS members. Genetic associations were examined in six independent studies (N = 14,260) with a wide range of LOAD risk. Association analysis in a sub-sample of the LLFS cohort (N = 1739) evaluated the association of LOAD variants with beta amyloid (Aβ) levels.ResultsWe identified several single nucleotide polymorphisms (SNPs) in tight linkage disequilibrium within the MTUS2 gene associated with LOAD (rs73154407, p = 7.6 × 10-9). Association of MTUS2 variants with LOAD was observed in the five independent studies and was significantly stronger within high levels of Aβ42/40 ratio compared to lower amyloid.DiscussionMTUS2 encodes a microtubule associated protein implicated in the development and function of the nervous system, making it a plausible candidate to investigate LOAD biology.HighlightsLong-Life Family Study (LLFS) families may harbor late onset Alzheimer's dementia (LOAD) variants. LLFS whole genome sequence analysis identified MTUS2 gene variants associated with LOAD. The observed LLFS variants generalized to cohorts with wide range of LOAD risk. The association of MTUS2 with LOAD was stronger within high levels of beta amyloid. Our results provide evidence for MTUS2 gene as a novel LOAD candidate locus.

Objective: Routine health care visits offer the opportunity to screen older adults for symptoms of Alzheimer's disease (AD). Many women see their gynecologist as their primary health care provider. Given this unique relationship, the Women's Preventive Services Initiative and the American College of Obstetrics and Gynecology advocate for integrated care of women at all ages. It is well-established that women are at increased risk for AD, and memory screening of older women should be paramount in this effort. Research is needed to determine the feasibility and value of memory screening among older women at the well-woman visit. Materials and Methods: Women aged 60 and above completed a 5-item subjective memory screener at their well-woman visit at the Columbia University Integrated Women's Health Program. Women who endorsed any item were considered to have a positive screen and were given the option to pursue clinical evaluation. Rates of positive screens, item endorsement, and referral preferences were examined. Results: Of the 530 women approached, 521 agreed to complete the screener. Of those, 17.5% (n = 91) were classified as positive. The most frequently endorsed item was difficulty with memory or thinking compared with others the same age. Among women with positive screens, 57.5% were interested in pursuing clinical referrals to a memory specialist. Conclusion: Results support the feasibility and potential value of including subjective memory screening as part of a comprehensive well-woman program. Early identification of memory loss will enable investigation into the cause of memory symptoms and longitudinal monitoring of cognitive change. [ABSTRACT FROM AUTHOR]

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]

Objective: Despite recent attention to cognitive impairment in essential tremor, few studies examine rates of conversion to diagnoses of mild cognitive impairment and dementia. Development of dementia in essential tremor is associated with loss of functional ability and a doubling of mortality rate. This prospective, longitudinal study comprehensively reports the prevalence and incidence of, and the annual rates of conversion to, mild cognitive impairment and dementia in an essential tremor cohort. Methods: Patients underwent detailed cognitive assessments and were assigned diagnoses of normal cognition, mild cognitive impairment, or dementia. There were 222 patients at baseline (mean age = 79.3 ± 9.7 years), and 177 patients participated in follow‐up evaluations at 18, 36, 54, and 72 months (mean years of observation = 5.1 ± 1.7). Data were compared to those of historical controls and Parkinson disease patients. Results: The cumulative prevalence of dementia and average annual conversion rate of mild cognitive impairment to dementia were 18.5% and 12.2%, nearly three times higher than rates in the general population, and approximately one half the magnitude of those reported for Parkinson disease patients. The cumulative prevalence of mild cognitive impairment (26.6%) was almost double that of the general population, but less than that in Parkinson disease populations. Interpretation: We present the most complete exposition of the longitudinal trajectory of cognitive impairment in an essential tremor cohort yet presented. The prevalence of and conversion rates to dementia in essential tremor fall between those associated with the natural course of aging and the more pronounced rates observed in Parkinson disease. ANN NEUROL 2024;95:1193–1204 [ABSTRACT FROM AUTHOR]

Introduction: Essential tremor (ET) patients may exhibit a variety of non-motor features, including cognitive decline and depressive symptoms. Studies of several neurodegenerative diseases link depression to cognitive decline, suggesting depression is an early marker of dementia. We examined whether baseline depressive symptoms predict incident dementia in elders with ET. Methods: Hundred and forty-one ET cases aged 70 years or older at baseline, enrolled in a prospective study of cognitive performance, took part in evaluations at baseline and at 18, 36, 54, and 72 months. Participants completed the Geriatric Depression Scale (GDS), a 30-item self-report measure of depressive symptoms, and a battery of neuropsychological tests and functional assessments, from which we derived cognitive diagnoses at each evaluation. Cox proportional hazards regression equations determined incident dementia risk based on participants' baseline depression scores. Results: Mean baseline age was 81.5 ± 6.7 years. Higher baseline GDS scores were associated with increased risk of dementia in an unadjusted model (hazards ratio [HR] = 1.11, 95% confidence interval [CI] = 1.02–1.20, p = 0.01) and after controlling for baseline age, education, number of medications, and tremor onset age (HR = 1.13, 95% CI = 1.02–1.25, p = 0.02). Conclusion: Baseline depression scores predicted incident dementia in elders with ET. With each one-point increase in baseline depression score, there was a 13% increase in incident dementia risk. Given the published data that reported depression may be twice as high in elders with ET compared to controls, this association is particularly worrisome in the ET population. [ABSTRACT FROM AUTHOR]