Monitoring Gait and Physical Activity of Elderly Frail Individuals in Free-Living Environment: A Feasibility Study.

INTRODUCTION: Frailty is conventionally diagnosed using clinical tests and self-reported assessments. However, digital health technologies (DHTs), such as wearable accelerometers, can capture physical activity and gait during daily life, enabling more objective assessments. In this study, we assess the feasibility of deploying DHTs in community-dwelling older individuals, and investigate the relationship between digital measurements of physical activity and gait in naturalistic environments and participants' frailty status, as measured by conventional assessments. METHODS: Fried Frailty Score (FFS) was used to classify fifty healthy individuals as non-frail (FFS = 0, n/female = 21/11, mean ± SD age: 71.10 ± 3.59 years), pre-frail (FFS = 1-2, n/female = 23/9, age: 73.74 ± 5.52 years), or frail (FFS = 3+, n/female = 6/6, age: 70.70 ± 6.53 years). Participants wore wrist-worn and lumbar-worn GENEActiv accelerometers (Activinsights Ltd., Kimbolton, UK) during three in-laboratory visits, and at-home for 2 weeks, to measure physical activity and gait. After this period, they completed a comfort and usability questionnaire. Compliant days at-home were defined as follows: those with ≥18 h of wear time, for the wrist-worn accelerometer, and those with ≥1 detected walking bout, for the lumbar-worn accelerometer. For each at-home measurement, a group analysis was performed using a linear regression model followed by ANOVA, to investigate the effect of frailty on physical activity and gait. Correlation between at-home digital measurements and conventional in-laboratory assessments was also investigated. RESULTS: Participants were highly compliant in wearing the accelerometers, as 94% indicated willingness to wear the wrist device, and 66% the lumbar device, for at least 1 week. Time spent in sedentary activity and time spent in moderate activity as measured from the wrist device, as well as average gait speed and its 95th percentile from the lumbar device were significantly different between frailty groups. Moderate correlations between digital measurements and self-reported physical activity were found. CONCLUSIONS: This work highlights the feasibility of deploying DHTs in studies involving older individuals. The potential of digital measurements in distinguishing frailty phenotypes, while unobtrusively collecting unbiased data, thus minimizing participants' travels to sites, will be further assessed in a follow-up study.

Maximizing utility of neuropsychological measures in sex-specific predictive models of incident Alzheimer's disease in the Framingham Heart Study.

INTRODUCTION: Sex differences in neuropsychological (NP) test performance might have important implications for the diagnosis of Alzheimer's disease (AD). This study investigates sex differences in neuropsychological performance among individuals without dementia at baseline. METHODS: Neuropsychological assessment data, both standard test scores and process coded responses, from Framingham Heart Study participants were analyzed for sex differences using regression model and Cox proportional hazards model. Optimal NP profiles were identified by machine learning methods for men and women. RESULTS: Sex differences were observed in both summary scores and composite process scores of NP tests in terms of adjusted means and their associations with AD incidence. The optimal NP profiles for men and women have 10 and 8 measures, respectively, and achieve 0.76 mean area under the curve for AD prediction. DISCUSSION: These results suggest that NP tests can be leveraged for developing more sensitive, sex-specific indices for the diagnosis of AD.

Examination of potentially modifiable dementia risk factors across the adult life course: The Framingham Heart Study.

INTRODUCTION: We examined for associations between potentially modifiable risk factors across the adult life course and incident dementia. METHODS: Participants from the Framingham Heart Study were included (n = 4015). Potential modifiable risk factors included education, alcohol intake, smoking, body mass index (BMI), physical activity, social network, diabetes, and hypertension. Cox models were used to examine associations between each factor and incident dementia, stratified by early adult life (33-44 years), midlife (45-65 years), and late life (66-80 years). RESULTS: Increased dementia risk was associated with diabetes (hazard ratio [HR] = 1.62; 95% confidence interval [CI] = 1.07-2.46) and physical inactivity (HR = 1.57; 95% CI = 1.12-2.20) in midlife, and with obesity (HR = 1.76; 95% CI = 1.08-2.87) in late life. Having multiple potential modifiable risk factors in midlife and late life was associated with greater risk. DISCUSSION: Potentially modifiable risk factors individually have limited impact on dementia risk in this population across the adult life course, although in combination they may have a synergistic effect. HIGHLIGHTS: Diabetes and physical inactivity in midlife is associated with increased dementia risk. Obesity in late life is associated with increased dementia risk. Having more potentially modifiable risk factors in midlife and late life is associated with greater dementia risk.

Midlife lipid and glucose levels are associated with Alzheimer's disease.

INTRODUCTION: It is unknown whether vascular and metabolic diseases assessed in early adulthood are associated with Alzheimer's disease (AD) later in life. METHODS: Association of AD with lipid fractions, glucose, blood pressure, body mass index (BMI), and smoking obtained prospectively from 4932 Framingham Heart Study (FHS) participants across nine quadrennial examinations was evaluated using Cox proportional hazard and Kaplan-Meier models. Age-, sex-, and education-adjusted models were tested for each factor measured at each exam and within three adult age groups (early = 35-50, middle = 51-60, and late = 61-70). RESULTS: A 15 mg/dL increase in high density lipoprotein (HDL) cholesterol was associated with decreased AD risk during early (15.4%, P = 0.041) and middle (17.9%, P = 0.014) adulthood. A 15 mg/dL increase in glucose measured during middle adulthood was associated with 14.5% increased AD risk (P = 0.00029). These findings remained significant after adjusting for treatment. DISCUSSION: Our findings suggest that careful management of cholesterol and glucose beginning in early adulthood can lower AD risk.

Associations Between the Digital Clock Drawing Test and Brain Volume: Large Community-Based Prospective Cohort (Framingham Heart Study).

BACKGROUND: The digital Clock Drawing Test (dCDT) has been recently used as a more objective tool to assess cognition. However, the association between digitally obtained clock drawing features and structural neuroimaging measures has not been assessed in large population-based studies. OBJECTIVE: We aimed to investigate the association between dCDT features and brain volume. METHODS: This study included participants from the Framingham Heart Study who had both a dCDT and magnetic resonance imaging (MRI) scan, and were free of dementia or stroke. Linear regression models were used to assess the association between 18 dCDT composite scores (derived from 105 dCDT raw features) and brain MRI measures, including total cerebral brain volume (TCBV), cerebral white matter volume, cerebral gray matter volume, hippocampal volume, and white matter hyperintensity (WMH) volume. Classification models were also built from clinical risk factors, dCDT composite scores, and MRI measures to distinguish people with mild cognitive impairment (MCI) from those whose cognition was intact. RESULTS: A total of 1656 participants were included in this study (mean age 61 years, SD 13 years; 50.9% women), with 23 participants diagnosed with MCI. All dCDT composite scores were associated with TCBV after adjusting for multiple testing (P value <.05/18). Eleven dCDT composite scores were associated with cerebral white matter volume, but only 1 dCDT composite score was associated with cerebral gray matter volume. None of the dCDT composite scores was associated with hippocampal volume or WMH volume. The classification model for differentiating MCI and normal cognition participants, which incorporated age, sex, education, MRI measures, and dCDT composite scores, showed an area under the curve of 0.897. CONCLUSIONS: dCDT composite scores were significantly associated with multiple brain MRI measures in a large community-based cohort. The dCDT has the potential to be used as a cognitive assessment tool in the clinical diagnosis of MCI.

Mid- to Late-Life Body Mass Index and Dementia Risk: 38 Years of Follow-up of the Framingham Study.

Growing evidence relates body mass index (BMI) to poorer health outcomes; however, results across studies associating BMI and dementia are conflicting. A total of 3,632 Framingham Offspring participants aged 20 to 60 years at their second health examination (1979-1983) were included in this study, with 190 cases of incident dementia identified by 2017. Cox proportional hazards regression models were fitted to investigate the association of BMI at each of their 8 exams as a baseline for dementia risk and the associations between obesity and dementia across age groups. Spline models were fitted to investigate nonlinear associations between BMI and dementia. Each 1-unit increase in BMI at ages 40-49 years was associated with higher risk of dementia, but with lower risk after age 70 years. Obesity at ages 40-49 years was associated with higher risk of dementia. Overall, the relationship between BMI and dementia risk was heterogeneous across the adult age range. Monitoring BMI at different ages might mediate risk for dementia across an individual's lifetime.

Development and validation of an interpretable deep learning framework for Alzheimer's disease classification.

Alzheimer's disease is the primary cause of dementia worldwide, with an increasing morbidity burden that may outstrip diagnosis and management capacity as the population ages. Current methods integrate patient history, neuropsychological testing and MRI to identify likely cases, yet effective practices remain variably applied and lacking in sensitivity and specificity. Here we report an interpretable deep learning strategy that delineates unique Alzheimer's disease signatures from multimodal inputs of MRI, age, gender, and Mini-Mental State Examination score. Our framework linked a fully convolutional network, which constructs high resolution maps of disease probability from local brain structure to a multilayer perceptron and generates precise, intuitive visualization of individual Alzheimer's disease risk en route to accurate diagnosis. The model was trained using clinically diagnosed Alzheimer's disease and cognitively normal subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset (n = 417) and validated on three independent cohorts: the Australian Imaging, Biomarker and Lifestyle Flagship Study of Ageing (AIBL) (n = 382), the Framingham Heart Study (n = 102), and the National Alzheimer's Coordinating Center (NACC) (n = 582). Performance of the model that used the multimodal inputs was consistent across datasets, with mean area under curve values of 0.996, 0.974, 0.876 and 0.954 for the ADNI study, AIBL, Framingham Heart Study and NACC datasets, respectively. Moreover, our approach exceeded the diagnostic performance of a multi-institutional team of practicing neurologists (n = 11), and high-risk cerebral regions predicted by the model closely tracked post-mortem histopathological findings. This framework provides a clinically adaptable strategy for using routinely available imaging techniques such as MRI to generate nuanced neuroimaging signatures for Alzheimer's disease diagnosis, as well as a generalizable approach for linking deep learning to pathophysiological processes in human disease.

Association Between the Digital Clock Drawing Test and Neuropsychological Test Performance: Large Community-Based Prospective Cohort (Framingham Heart Study).

BACKGROUND: The Clock Drawing Test (CDT) has been widely used in clinic for cognitive assessment. Recently, a digital Clock Drawing Text (dCDT) that is able to capture the entire sequence of clock drawing behaviors was introduced. While a variety of domain-specific features can be derived from the dCDT, it has not yet been evaluated in a large community-based population whether the features derived from the dCDT correlate with cognitive function. OBJECTIVE: We aimed to investigate the association between dCDT features and cognitive performance across multiple domains. METHODS: Participants from the Framingham Heart Study, a large community-based cohort with longitudinal cognitive surveillance, who did not have dementia were included. Participants were administered both the dCDT and a standard protocol of neuropsychological tests that measured a wide range of cognitive functions. A total of 105 features were derived from the dCDT, and their associations with 18 neuropsychological tests were assessed with linear regression models adjusted for age and sex. Associations between a composite score from dCDT features were also assessed for associations with each neuropsychological test and cognitive status (clinically diagnosed mild cognitive impairment compared to normal cognition). RESULTS: The study included 2062 participants (age: mean 62, SD 13 years, 51.6% women), among whom 36 were diagnosed with mild cognitive impairment. Each neuropsychological test was associated with an average of 50 dCDT features. The composite scores derived from dCDT features were significantly associated with both neuropsychological tests and mild cognitive impairment. CONCLUSIONS: The dCDT can potentially be used as a tool for cognitive assessment in large community-based populations.

Exploring the Hierarchical Influence of Cognitive Functions for Alzheimer Disease: The Framingham Heart Study.

BACKGROUND: Although some neuropsychological (NP) tests are considered more central for the diagnosis of Alzheimer disease (AD), there is a lack of understanding about the interaction between different cognitive tests. OBJECTIVE: This study aimed to demonstrate a global view of hierarchical probabilistic dependencies between NP tests and the likelihood of cognitive impairment to assist physicians in recognizing AD precursors. METHODS: Our study included 2091 participants from the Framingham Heart Study. These participants had undergone a variety of NP tests, including Wechsler Memory Scale, Wechsler Adult Intelligence Scale, and Boston Naming Test. Heterogeneous cognitive Bayesian networks were developed to understand the relationship between NP tests and the cognitive status. The performance of probabilistic inference was evaluated by the 10-fold cross validation. RESULTS: A total of 4512 NP tests were used to build the Bayesian network for the dementia diagnosis. The network demonstrated conditional dependency between different cognitive functions that precede the development of dementia. The prediction model reached an accuracy of 82.24%, with sensitivity of 63.98% and specificity of 92.74%. This probabilistic diagnostic system can also be applied to participants that exhibit more heterogeneous profiles or with missing responses for some NP tests. CONCLUSIONS: We developed a probabilistic dependency network for AD diagnosis from 11 NP tests. Our study revealed important psychological functional segregations and precursor evidence of AD development and heterogeneity.

Practical risk score for 5-, 10-, and 20-year prediction of dementia in elderly persons: Framingham Heart Study.

INTRODUCTION: With a rapidly aging population, general practitioners are confronting the challenge of how to determine those who are at greatest risk for dementia and potentially need more specialized follow-up to mitigate symptoms early in its course. We created a practical dementia risk score and provided individualized estimates of future dementia risk. METHODS: Using the Framingham Heart Study data, we built our prediction model using Cox proportional hazard models and developed a point system for the risk score and risk estimates. RESULTS: The score system used total points ranging from -1 to 31 and stratifies individuals into different levels of risk. We estimated 5-, 10-, and 20-year dementia risk prediction and incorporated these into the points system. DISCUSSION: This risk score system provides a practical tool because all included predictors are easy to assess by practitioners. It can be used to estimate future probabilities of dementia for individuals.

Association between neuropathology and brain volume in the Framingham Heart Study.

Studies of clinical and community cohorts have shown that antemortem imaging measures of hippocampal volume have correlated with postmortem Alzheimer pathology. Fewer studies have examined the relationship between both Alzheimer and cerebrovascular pathology, and antemortem brain imaging. The aim of this study was to correlate antemortem brain magnetic resonance imaging (MRI) volumes with postmortem brain pathology (both Alzheimer-related and cerebrovascular) in a community-derived cohort from the Framingham Heart Study. Participants (n=59) from the Framingham Heart Study were included if they were enrolled in the brain autopsy program and underwent antemortem clinical evaluation, neuropsychological testing, and brain MRI. Cortical neurofibrillary tangle pathology correlated with lower total cerebral brain (ß±SE=-0.04±0.01, P=0.004) and hippocampal volumes (ß±SE=-0.03±0.02, P=0.044) and larger temporal horns (log-transformed, ß±SE=0.05±0.01, P=0.001). Similar findings were seen between total/cortical neuritic plaques and total cerebral brain and temporal horn volume. White matter hyperintensities (also log-transformed) were best predicted by the presence of deep nuclei microinfarcts (ß±SE=0.53±0.21, P=0.016), whereas hippocampal volume was significantly decreased in the presence of hippocampal sclerosis (ß±SE=-1.23±0.30, P<0.001). This study showed that volumetric MRI measures correlated with postmortem Alzheimer-related and cerebrovascular neuropathology in this community-derived cohort, confirming that these MRI measures are important antemortem surrogates for these dementia-related pathologies.

Central sleep apnea and complex sleep apnea in patients with epilepsy.

PURPOSE: We sought to examine the prevalence of central sleep apnea (CSA) and complex sleep apnea (CompSA) in patients with epilepsy and to examine their clinical profile, with respect to epilepsy type, etiology, medication use, and EEG abnormalities. METHODS: We undertook a retrospective analysis of 719 consecutive patients with epilepsy who underwent polysomnography (PSG) at our institution between 2004 and 2011. Of the 458 patients with complete data, we excluded 42 patients with congestive heart failure or left ventricular ejection fraction <40 %. Comparison of clinical and PSG variables between the three groups were conducted with Fisher exact test and analysis of variance. RESULTS: Out of 416 patients tested, 315 (75 %) had obstructive sleep apnea (OSA), 16 (3.7 %) had CSA, 33 (7.9 %) had CompSA. There were more males in the CSA and CompSA groups than in the OSA group (81.2, 81.8, and 59.6 %, respectively, p=0.04). Focal seizures were more prevalent in patients with CSA than in patients OSA or CompSA (62.5, 265, and 21.1 %, respectively, p=0.02). CONCLUSION: About 11 % of epilepsy patients have sleep-breathing disorders with central apneas, which is not higher than that in a general population. These data should be expanded with future research investigating the role of interictal, ictal, and postictal central apneas in epileptogenesis and epilepsy.

Efficacy and safety of insomnia treatment with lemborexant in older adults: analyses from three clinical trials.

BACKGROUND: Insomnia is more common as people age. Several common hypnotics used to treat insomnia often do not adequately alleviate sleep issues in older adults and may be associated with negative residual effects such as an increased risk of falls, cognitive impairment, automobile accidents, and lack of response to auditory stimuli. The objective of these analyses of three clinical studies was to investigate the efficacy and safety of the dual orexin-receptor antagonist lemborexant (LEM) in older adults. METHODS: Study E2006-G000-304 (Study 304; NCT02783729) was a randomized, double-blind, placebo (PBO)-controlled, active-comparator trial where subjects with insomnia disorder received LEM 5 mg (LEM5), LEM 10 mg (LEM10), zolpidem tartrate extended-release 6.25 mg (ZOL), or PBO for 30 days. In crossover Study E2006-E044-106 (Study 106; NCT02583451), healthy subjects (good sleepers) received LEM 2.5 mg, LEM5, LEM10, or PBO for eight nights or zopiclone on days 1 and 8 (and PBO on days 2-7). In crossover Study E2006-A001-108 (Study 108; NCT03008447), healthy subjects received a single dose of LEM5, LEM10, PBO, or ZOL. Sleep assessments included polysomnography-based latency to persistent sleep (LPS), wake after sleep onset (WASO), WASO in the second half of the night (WASO2H), sleep efficiency, postural stability, middle-of-the-night and next-day cognitive performance, middle-of-the-night auditory awakening threshold and return-to-sleep latency, and driving performance. RESULTS: Overall, 453 of 1006 (45%; Study 304), 24 of 48 (50%; Study 106), and 28 of 56 (50%; Study 108) subjects were aged ≥ 65 years. In Study 304, LEM decreased (improved) LPS, WASO, and WASO2H from baseline more than ZOL and PBO; subjects treated with LEM had greater increases in sleep efficiency (improved) than with ZOL or PBO. In both Studies 304 and 108, postural stability was not impaired at waketime in subjects who received LEM compared with PBO. At waketime, LEM did not impair memory compared with PBO. In Study 108, following middle-of-the-night awakening, LEM and ZOL did not affect subjects' ability to awaken to auditory stimuli; LEM did not affect tests of memory and attention. In Study 106, LEM did not impair next-day driving performance in healthy elderly compared with PBO. LEM was well tolerated in subjects aged ≥ 65 years. CONCLUSIONS: LEM provided benefits on sleep variables without next-morning residual effects in subjects aged ≥ 65 years, supporting LEM as a treatment option for older adults with insomnia. TRIAL REGISTRATION NUMBERS AND DATES OF REGISTRATION: Study 304: ClinicalTrials.gov identifier, NCT02783729, date of registration, 26 May 2016. Study 106: ClinicalTrials.gov identifier, NCT02583451, date of registration, 22 October 2015. Study 108: ClinicalTrials.gov identifier, NCT03008447, date of registration, 2 January 2017.

The prevalence of insomnia increases with age; however, some hypnotics used for treating insomnia do not adequately resolve sleep problems in older adults and may be associated with adverse residual effects. Specifically, some hypnotics pose safety concerns in this population of patients who are generally more vulnerable to treatment-related effects, including increasing the risk of falls, risks of cognitive impairment, automobile accidents, and unresponsiveness to auditory stimuli. Safer and more effective insomnia medications are needed to reduce sleep problems with improved side-effect profiles. This analysis of lemborexant clinical studies conducted in adult subjects at least 65 years old found the drug to be effective without impairing memory, attention or balance the following day compared with placebo. These subjects were normal sleepers (for age) or had insomnia disorder. Furthermore, lemborexant was not associated with impaired ability to drive the next morning or awaken to loud middle-of-the-night sounds. Lemborexant was well tolerated in these older adults, similar to findings for adults aged at least 18 years. These findings indicate that lemborexant may be an appropriate treatment option for insomnia in older adults.

Subjective Cognitive Decline Plus and Longitudinal Assessment and Risk for Cognitive Impairment.

Importance: Subjective cognitive decline (SCD) is recognized to be in the Alzheimer disease (AD) cognitive continuum. The SCD Initiative International Working Group recently proposed SCD-plus (SCD+) features that increase risk for future objective cognitive decline but that have not been assessed in a large community-based setting. Objective: To assess SCD risk for mild cognitive impairment (MCI), AD, and all-cause dementia, using SCD+ criteria among cognitively normal adults. Design, Setting, and Participants: The Framingham Heart Study, a community-based prospective cohort study, assessed SCD between 2005 and 2019, with up to 12 years of follow-up. Participants 60 years and older with normal cognition at analytic baseline were included. Cox proportional hazards (CPH) models were adjusted for baseline age, sex, education, APOE ε4 status, and tertiles of AD polygenic risk score (PRS), excluding the APOE region. Data were analyzed from May 2021 to November 2023. Exposure: SCD was assessed longitudinally using a single question and considered present if endorsed at the last cognitively normal visit. It was treated as a time-varying variable, beginning at the first of consecutive, cognitively normal visits, including the last, at which it was endorsed. Main Outcomes and Measures: Consensus-diagnosed MCI, AD, and all-cause dementia. Results: This study included 3585 participants (mean [SD] baseline age, 68.0 [7.7] years; 1975 female [55.1%]). A total of 1596 participants (44.5%) had SCD, and 770 (21.5%) were carriers of APOE ε4. APOE ε4 and tertiles of AD PRS status did not significantly differ between the SCD and non-SCD groups. MCI, AD, and all-cause dementia were diagnosed in 236 participants (6.6%), 73 participants (2.0%), and 89 participants (2.5%), respectively, during follow-up. On average, SCD preceded MCI by 4.4 years, AD by 6.8 years, and all-cause dementia by 6.9 years. SCD was significantly associated with survival time to MCI (hazard ratio [HR], 1.57; 95% CI, 1.22-2.03; P <.001), AD (HR, 2.98; 95% CI, 1.89-4.70; P <.001), and all-cause dementia (HR, 2.14; 95% CI, 1.44-3.18; P <.001). After adjustment for APOE and AD PRS, the hazards of SCD were largely unchanged. Conclusions and Relevance: Results of this cohort study suggest that in a community setting, SCD reflecting SCD+ features was associated with an increased risk of future MCI, AD, and all-cause dementia with similar hazards estimated in clinic-based settings. SCD may be an independent risk factor for AD and other dementias beyond the risk incurred by APOE ε4 and AD PRS.

Defining MCI in the Framingham Heart Study Offspring: education versus WRAT-based norms.

INTRODUCTION: Psychometric definitions of mild cognitive impairment (MCI) typically use cut-off levels set at 1.5 SDs below age-adjusted and education-adjusted norms, assuming that the education adjustment accounts for premorbid abilities. However, noncognitive factors impact educational attainment, potentially leading to incorrect categorization as MCI. We examined whether using an adjustment based on reading performance [Wide Range Achievement Test (WRAT) Reading] improved MCI diagnostic accuracy. METHODS: A total of 935 Framingham Offspring (mean age, 72±5 y) underwent tests of memory, executive function, abstraction, language, and visuospatial function as part of a neuropsychological test battery. Domain-specific test scores were regressed onto age and WRAT score, or education, to define MCI. Survival analyses were used to relate baseline MCI to incident dementia. RESULTS: The 2 MCI definitions differed most for the lowest and highest education groups. The WRAT definition was more strongly associated with incident dementia for all 5 tests. MCI level abstraction performance was associated with incident dementia using the WRAT definition (HR=3.20, P=0.033), but not the education definition (HR=1.19, P=0.814). DISCUSSION: The WRAT should be considered along with the standard measure of years of education, as it may be a better surrogate marker of premorbid abilities.

Lexical retrieval in discourse: an early indicator of Alzheimer's dementia.

We examined the progression of lexical-retrieval deficits in individuals with neuropathologically determined Alzheimer's disease (AD; n = 23) and a comparison group without criteria for AD (n = 24) to determine whether linguistic changes were a significant marker of the disease. Our participants underwent multiple administrations of a neuropsychological battery, with initial administration occurring on average 16 years prior to death. The battery included the Boston Naming Test (BNT), a letter fluency task (FAS) and written description of the Cookie Theft Picture (CTP). Repeated measures analysis revealed that the AD-group showed progressively greater decline in FAS and CTP lexical performance than the comparison group. Cross-sectional time-specific group comparisons indicated that the CTP differentiated performance between the two groups at 7-9 years prior to death and FAS and BNT only at 2-4 years. These results suggest that lexical-retrieval deficits in written discourse serve as an early indicator of AD.

A machine learning eye movement detection algorithm using electrooculography.

STUDY OBJECTIVES: Eye movement quantification in polysomnograms (PSG) is difficult and resource intensive. Automated eye movement detection would enable further study of eye movement patterns in normal and abnormal sleep, which could be clinically diagnostic of neurologic disorders, or used to monitor potential treatments. We trained a long short-term memory (LSTM) algorithm that can identify eye movement occurrence with high sensitivity and specificity. METHODS: We conducted a retrospective, single-center study using one-hour PSG samples from 47 patients 18-90 years of age. Team members manually identified and trained an LSTM algorithm to detect eye movement presence, direction, and speed. We performed a 5-fold cross validation and implemented a "fuzzy" evaluation method to account for misclassification in the preceding and subsequent 1-second of gold standard manually labeled eye movements. We assessed G-means, discrimination, sensitivity, and specificity. RESULTS: Overall, eye movements occurred in 9.4% of the analyzed EOG recording time from 47 patients. Eye movements were present 3.2% of N2 (lighter stages of sleep) time, 2.9% of N3 (deep sleep), and 19.8% of REM sleep. Our LSTM model had average sensitivity of 0.88 and specificity of 0.89 in 5-fold cross validation, which improved to 0.93 and 0.92 respectively using the fuzzy evaluation scheme. CONCLUSION: An automated algorithm can detect eye movements from EOG with excellent sensitivity and specificity. Noninvasive, automated eye movement detection has several potential clinical implications in improving sleep study stage classification and establishing normal eye movement distributions in healthy and unhealthy sleep, and in patients with and without brain injury.

Is dietary choline intake related to dementia and Alzheimer's disease risks? Results from the Framingham Heart Study.

BACKGROUND: The positive association of choline for cognition has been reported in both animal and human studies, yet the associations of choline with the risks of incident dementia or Alzheimer's disease (AD) in humans is unclear. OBJECTIVES: Our objective was to test the hypothesis that lower or higher dietary choline intake is associated with increased or decreased, respectively, risks of incident dementia and AD. METHODS: Data from the Framingham Heart Study Offspring Cohort exam 5 to exam 9 were used. Participants were free of dementia and stroke, with a valid self-reported 126-item Harvard FFQ at exam 5. The intakes of total choline, its contributing compounds, and betaine were estimated based on a published nutrient database. The intakes were updated at each exam to represent the cumulative average intake across the 5 exams. The associations between dietary choline intakes and incident dementia and AD were examined in mixed-effect Cox proportional hazard models, adjusting for covariates. RESULTS: A total of 3224 participants (53.8% female; mean ± SD age, 54.5 ± 9.7 y) were followed up for a mean ± SD of 16.1 ± 5.1 y (1991-2011). There were 247 incident dementia cases, of which 177 were AD. Dietary choline intake showed nonlinear relationships with incident dementia and AD. After adjusting for covariates, low choline intake (defined as ≤ 219 and ≤ 215 mg/d for dementia and AD, respectively) was significantly associated with incident dementia and incident AD. CONCLUSIONS: Low choline intake was associated with increased risks of incident dementia and AD.

Effect of continuous positive airway pressure treatment on seizure control in patients with obstructive sleep apnea and epilepsy.

In patients with epilepsy, improvement in seizure control with treatment of coexisting obstructive sleep apnea (OSA) has been reported, but there is lack of data on the effect of continuous positive airway pressure (CPAP) compliance on seizure control in these patients. We examined the variability in seizure frequency in patients who were CPAP compliant and those who were not CPAP compliant. We undertook a retrospective review of clinical and polysomnographic data of adult patients with OSA and epilepsy seen at the Boston University Medical Center Epilepsy and Sleep Clinics between 2000 and 2010. Data were reviewed for CPAP compliance and seizure frequency after at least 6 months of CPAP use. Only patients with no changes in antiepileptic drug regimens during CPAP trial were included. Of the 660 patients identified, 41 fulfilled inclusion criteria, of whom 28 were CPAP compliant and 13 were not CPAP compliant. In the compliant group, CPAP use led to decreased seizure frequency from 1.8 per month to 1 per month (p = 0.01). In the noncompliant group, no significant difference in seizure frequency was noted between baseline (2.1 per month) and at follow-up (1.8 per month, p = 0.36). Sixteen of 28 CPAP-compliant subjects were seizure free, whereas only 3 of 13 non-CPAP compliant subjects were seizure free [relative risk (RR) 1.54, p = 0.05]. Patients with epilepsy and OSA not compliant with CPAP treatment are at higher risk of seizures than are CPAP-compliant patients. To validate this observation, further prospective studies are warranted.

Sleep architecture and sleep-related mentation in securely and insecurely attached people.

Based on REM sleep's brain activation patterns and its participation in consolidation of emotional memories, we tested the hypothesis that measures of REM sleep architecture and REM sleep-related mentation would be associated with attachment orientation. After a habituation night in a sleep lab, a convenience sample of 64 healthy volunteers were awakened 10 minutes into a REM sleep episode and 10 minutes into a control NREM sleep episode in counterbalanced order, then asked to report a dream and to rate themselves and a significant other on a list of trait adjectives. Relative to participants classified as having secure attachment orientations, participants classified as anxious took less time to enter REM sleep and had a higher frequency of REM dreams with aggression and self-denigrating themes. There were no significant differences across attachment groups in other measures of sleep architecture or in post REM-sleep awakening ratings on PANAS subscales reflecting mood and alertness. Selected aspects of REM sleep architecture and mentation appeared to be associated with attachment orientation. We suggest that REM sleep plays a role in processing experiences and emotions related to attachment, and that certain features of sleep and dreaming reflect attachment orientations.