The Relationship Between First Presenting Neuropsychiatric Symptoms in Older Adults and Autopsy-Confirmed Memory Disorders.

OBJECTIVES: Although dementia is typically considered a disease of cognitive decline, almost all patients present with neuropsychiatric symptoms (NPS) at some stage of their disease. Few studies have assessed the timing of NPS onset in relation to pathological diagnoses of neurodegenerative diseases. We sought to examine the association between the first presenting clinically significant NPS in aging individuals and neuropathological diagnoses of memory disorders. DESIGN: This retrospective longitudinal cohort study utilized the National Alzheimer's Coordinating Center (NACC) dataset, which includes participant data from 37 Alzheimer's Disease Research Centers collected between 2005 and 2022. PARTICIPANTS: Participants (N = 5,416) aged 45 years or older with Clinical Dementia Rating-Global ratings of less than or equal to 1 were included in this analysis. A total of 4,033 (74.5%) participants presented with at least one NPS at any NACC visit. MEASUREMENTS: To measure first NPS, the NACCBEHF variable was used, a clinician-rated variable defined as "the predominant symptom that was first recognized as a decline in the subject's behavior." Neuropathologic variables included assessments of Alzheimer's Disease, Frontotemporal Dementia, Lewy Body Dementia, Cerebral Amyloid Angiopathy, Hippocampal Sclerosis, and Cerebrovascular Disease. RESULTS: Presentation with any clinically significant first NPS was associated with several neuropathological diagnoses including Alzheimer's Disease, Frontotemporal Lobar Dementia with TDP-43 pathology, and Lewy Body Dementia. While specific first NPS were associated with Frontotemporal Dementia neuropathology (personality change and disinhibition) and Lewy Body Dementia neuropathology (psychosis and REM behavior disturbance), Alzheimer's Disease neuropathology was associated with the majority of NPS. CONCLUSIONS: Since neuropsychiatric symptoms are frequently the first presenting symptom of dementia, their associations with well-defined neuropathological diagnoses may help clinicians predict the subtype of future dementias.

Measuring Change over Time on Cognitive Screening Measures: An Evaluation of the Psychometric Properties of ACE-III, CBI-R, and EMQ for the Purpose of Dementia Screening.

INTRODUCTION: Cognitive screening measures are an established part of a dementia assessment and often include measures of subjective difficulties, e.g., Everyday Memory Questionnaire (EMQ), informant-rated difficulty, Cambridge Behavioural Inventory - Revised (CBI-R), and objective cognitive assessments like Addenbrooke's Cognitive Examination (ACE-III). While these measures have validity for the purpose of diagnosing dementia, in clinical practice they are often used outside of their evidence base for the purpose of cognitive re-assessment. The current study sought to evaluate the psychometric properties for the repeated use of these assessments. METHODS: This study used a longitudinal design, which included 49 healthy controls, 33 people with subjective memory difficulties, and 10 people with Alzheimer's disease (AD) being assessed twice, with approximately a 1-year interval between assessments. RESULTS: The EMQ has adequate re-test reliability (r = 0.78), but people with an AD diagnosis rated their memory as better than those with SMD, making it unsuitable as a measure. The CBI-R had moderate re-test reliability (r = 0.62). However, deterioration on the CBI-R was not useful for diagnosing AD. The ACE-III has high re-test reliability (r = 0.89). A change of five was associated with reasonable classification accuracy for identifying AD and achieved statistical significance. CONCLUSION: Using a 1-year interval, of the three measures used in this study, only the ACE-III total score may be a useful measure of change over time, although it should be applied cautiously due to the lack of representativeness of the sample, and change scores should always be triangulated with other forms of evidence of deterioration.

Drivers of Memory Loss Underreport in Mild Cognitive Impairment Due to Alzheimer Versus Vascular Disease.

BACKGROUND: We examined drivers of self and study partner reports of memory loss in mild cognitive impairment (MCI) from Alzheimer (AD-MCI) and vascular disease (Va-MCI). METHODS: We performed retrospective cross-sectional analyses of participants with AD-MCI (n=2874) and Va-MCI (n=376) from the National Alzheimer Coordinating Center data set. Statistical analysis utilized 2-sided t test or the Fisher exact test. RESULTS: Compared with AD-MCI, Va-MCI subjects (24.5% vs. 19.7%, P =0.031) and study partners (31.4% vs. 21.6%, P <0.0001) were more likely to deny memory loss. Black/African Americans were disproportionately represented in the group denying memory loss in AD-MCI (20.0% vs. 13.2%, P <0.0001) and Va-MCI (33.7% vs. 18.0%, P =0.0022). Study partners of participants with these features also disproportionately denied memory loss: female (AD-MCI: 60.1% vs. 51.7%, P =0.0002; Va-MCI: 70.3% vs. 52.3%, P =0.0011), Black/African American (AD-MCI: 23.5% vs. 11.98%, P <0.0001; Va-MCI: 48.8% vs. 26.5%, P =0.0002), and <16 years of education (AD-MCI only: 33.9% vs. 16.3%, P =0.0262). In AD-MCI and Va-MCI, participants with anxiety were disproportionately represented in the group endorsing memory loss (AD: 28.2% vs. 17.4%, P <0.0001; Va: 31.5% vs. 16.1%, P =0.0071), with analogous results with depression. CONCLUSION: The findings would suggest extra vigilance in interview-based MCI detection of persons at-risk for self-based or informant-based misreport.

A clinical 3D pointing test differentiates spatial memory deficits in dementia and bilateral vestibular failure.

BACKGROUND: Deficits in spatial memory, orientation, and navigation are often neglected early signs of cognitive impairment or loss of vestibular function. Real-world navigation tests require complex setups. In contrast, simple pointing at targets in a three-dimensional environment is a basic sensorimotor ability which provides an alternative measure of spatial orientation and memory at bedside. The aim of this study was to test the reliability of a previously established 3D-Real-World Pointing Test (3D-RWPT) in patients with cognitive impairment due to different neurodegenerative disorders, bilateral vestibulopathy, or a combination of both compared to healthy participants. METHODS: The 3D-RWPT was performed using a static array of targets in front of the seated participant before and, as a transformation task, after a 90-degree body rotation around the yaw-axis. Three groups of patients were enrolled: (1) chronic bilateral vestibulopathy (BVP) with normal cognition (n = 32), (2) cognitive impairment with normal vestibular function (n = 28), and (3) combined BVP and cognitive impairment (n = 9). The control group consisted of age-matched participants (HP) without cognitive and vestibular deficits (n = 67). Analyses focused on paradigm-specific mean angular deviation of pointing in the azimuth (horizontal) and polar (vertical) spatial planes, of the preferred pointing strategy (egocentric or allocentric), and the resulting shape configuration of the pointing array relative to the stimulus array. Statistical analysis was performed using age-corrected ANCOVA-testing with Bonferroni correction and correlation analysis using Spearman's rho. RESULTS: Patients with cognitive impairment employed more egocentric pointing strategies while patients with BVP but normal cognition and HP used more world-based solutions (pBonf 5.78 × 10-3**). Differences in pointing accuracy were only found in the azimuth plane, unveiling unique patterns where patients with cognitive impairment showed decreased accuracy in the transformation tasks of the 3D-RWPT (pBonf < 0.001***) while patients with BVP struggled in the post-rotation tasks (pBonf < 0.001***). Overall azimuth pointing performance was still adequate in some patients with BVP but significantly decreased when combined with a cognitive deficit. CONCLUSION: The 3D-RWPT provides a simple and fast measure of spatial orientation and memory. Cognitive impairment often led to a shift from world-based allocentric pointing strategy to an egocentric performance with less azimuth accuracy compared to age-matched controls. This supports the view that cognitive deficits hinder the mental buildup of the stimulus pattern represented as a geometrical form. Vestibular hypofunction negatively affected spatial memory and pointing performance in the azimuth plane. The most severe spatial impairments (angular deviation, figure frame configuration) were found in patients with combined cognitive and vestibular deficits.

Novelty preference assessed by eye tracking: A sensitive measure of impaired recognition memory in epilepsy.

OBJECTIVE: Epilepsy patients often report memory deficits despite normal objective testing, suggesting that available measures are insensitive or that non-mnemonic factors are involved. The Visual Paired Comparison Task (VPCT) assesses novelty preference, the tendency to fixate on novel images rather than previously viewed items, requiring recognition memory for the "old" images. As novelty preference is a sensitive measure of hippocampal-dependent memory function, we predicted impaired VPCT performance in epilepsy patients compared to healthy controls. METHODS: We assessed 26 healthy adult controls and 31 epilepsy patients (16 focal-onset, 13 generalized-onset, 2 unknown-onset) with the VPCT using delays of 2 or 30 s between encoding and recognition. Fifteen healthy controls and 17 epilepsy patients (10 focal-onset, 5 generalized-onset, 2 unknown-onset) completed the task at 2-, 5-, and 30-minute delays. Subjects also performed standard memory measures, including the Medical College of Georgia (MCG) Paragraph Test, California Verbal Learning Test-Second Edition (CVLT-II), and Brief Visual Memory Test-Revised (BVMT-R). RESULTS: The epilepsy group was high functioning, with greater estimated IQ (p = 0.041), greater years of education (p = 0.034), and higher BVMT-R scores (p = 0.024) compared to controls. Both the control group and epilepsy cohort, as well as focal- and generalized-onset subgroups, had intact novelty preference at the 2- and 30-second delays (p-values ≤ 0.001) and declined at 30 min (p-values > 0.05). Only the epilepsy patients had early declines at 2- and 5-minute delays (controls with intact novelty preference at p = 0.003 and p ≤ 0.001, respectively; epilepsy groups' p-values > 0.05). CONCLUSIONS: Memory for the "old" items decayed more rapidly in overall, focal-onset, and generalized-onset epilepsy groups. The VPCT detected deficits while standard memory measures were largely intact, suggesting that the VPCT may be a more sensitive measure of temporal lobe memory function than standard neuropsychological batteries.

Utility of automated memory measures in identifying cognitive impairment in adults with epilepsy.

OBJECTIVE: Cognitive impairment is prevalent in epilepsy and often presents at the time of initial diagnosis. This study sought to validate brief, self-administered, iPad-based recognition memory tasks in a sample of patients with epilepsy and to examine their screening utility in identifying patients with cognitive impairment. METHODS: The Words and Faces tests were administered to 145 adult patients with epilepsy along with a neuropsychological battery. Correlation analyses examined the convergent and divergent validity of the Words and Faces tests, and a series of logistic regression analyses examined discriminative ability in identifying patients with and without cognitive impairments on neuropsychological measures. Patient performance was compared to that of a healthy control group (n = 223), and the relationship between the Words and Faces test performance and disease-related variables (i.e., antiepileptic medication burden, seizure lateralization/localization) was examined. RESULTS: The Words and Faces tests were positively correlated with traditional paper-and-pencil neuropsychological measures of episodic memory, with generally moderate to large effect sizes (r > .40), while correlations between the Words and Faces tests and non-memory measures were generally small in magnitude (r < .30). Patients with epilepsy had significantly lower scores on Words and Faces tests compared to healthy controls, and performance was associated with antiepileptic medication burden and seizure localization. The Words and Faces tests demonstrated good predictive accuracy in identifying any cognitive impairment (concordance (c) statistic = .77) and excellent predictive accuracy (c = .85) in identifying patients with impairments on traditional memory measures. The Words and Faces tests also demonstrated reasonable discrimination for impairments in non-memory domains including executive function, language, attention, processing speed, and visuospatial ability (c = .62 -.70). Importantly, the Words and Faces Immediate Index performed just as well as the Total Score (which included delayed memory performance), suggesting a short version of this measure is sufficient for identifying patients with cognitive impairment. CONCLUSIONS: The Words and Faces tests are valid, computerized tools that can be used to screen for memory and other cognitive impairment in adults with epilepsy.

Normative data beyond the total scores: a process score analysis of the Rey's 15 word test in healthy aging and Alzheimer's Disease.

BACKGROUND: The Rey's 15 words test is currently the most frequently used task in Italy to detect memory deficits in AD. The current standardised version is however quite outdated and lacks some cognitive indexes which may highlight problems in recall or encoding processes. The aim of the study was to update the normative data of the test and to consider some variables which were not accounted for in the original study, that is, recognition, learning rate and forgetfulness. We also adopted the process scores approach to ascertain the effects of serial position (primacy and recency). METHODS: Three hundred ninety-six healthy participants were recruited. To detect any variables useful for intercepting the early stages of dementia, a group of 208 patients in the very early stage of AD was also recruited. Linear models were used to calculate the corrections scores for age, education, and gender, and ROCs were used to calculate cut-offs based on the maximum sum of sensitivity and specificity and the positive and negative predictive values. RESULTS: All main indexes showed excellent Area Under the Curve (0.90-1), strong sensitivity and PPVs for distinguishing between the HCs and AD participants. However, the Intrusions index performed poorly in all parameters. CONCLUSION: The study provides updated, normative data which may be reliably used as a cognitive marker to detect early AD. The strength of the study is the large sample size and the number of indexes which make it possible to explore the utility of memory test process scores.

Predictors for the development of motoric cognitive risk syndrome in older adults.

BACKGROUND: Motoric cognitive risk (MCR) syndrome refers to a condition where both slow gait and memory complaints coexist, which heightens their vulnerability to developing dementia. Considering that the risk factors of MCR are elucidated from cross-sectional studies and also likely vary based on socioeconomic status, we conducted a community-based longitudinal study to determine the predictors of MCR among older adults in Malaysia. METHODS: Out of 1,249 older participants (aged 60 years and above) without MCR at baseline (Wave II of LRGS-TUA cohort study), 719 were successfully followed up after 3.5 years to identify predictors of subsequent MCR development. A comprehensive interview-based questionnaire was administered for sociodemographic information, cognitive function, psychosocial, functional status, and dietary intake. Anthropometric measurements, body composition, and physical performance were assessed. Univariate analyses were performed for each variable, followed by a hierarchical logistic regression analysis to identify the predictors of MCR that accounted for confounding effects between the studied factors. RESULTS: The incidence rate of MCR was 4.0 per 100 person-years. Smoking (Adjusted Odd Ratio (Adj OR) = 1.782; 95% Confidence Interval (CI):1.050-3.024), hypertension (Adj OR = 1.725; 95% CI:1.094-2.721), decreased verbal memory as assessed by the lower Rey Auditory Verbal Learning Test (RAVLT) (Adj OR = 1.891; 95% CI:1.103-3.243), and decreased functional status measured using instrumental activity of daily living (IADL) (Adj OR = 4.710; 95% CI:1.319-16.823), were predictors for MCR incidence. CONCLUSIONS: Our study results provide an initial reference for future studies to formulate effective preventive management and intervention strategies to reduce the growing burden of adverse health outcomes, particularly among Asian older adults.

Estimating presymptomatic episodic memory impairment using simple hand movement tests: A cross-sectional study of a large sample of older adults.

INTRODUCTION: Finding low-cost methods to detect early-stage Alzheimer's disease (AD) is a research priority for neuroprotective drug development. Presymptomatic Alzheimer's is associated with gait impairment but hand motor tests, which are more accessible, have hardly been investigated. This study evaluated how home-based Tasmanian (TAS) Test keyboard tapping tests predict episodic memory performance. METHODS: 1169 community participants (65.8 ± 7.4 years old; 73% female) without cognitive symptoms completed online single-key and alternate-key tapping tests and episodic memory, working memory, and executive function cognitive tests. RESULTS: All single-key (R2 adj  = 8.8%, ΔAIC = 5.2) and alternate-key (R2 adj  = 9.1%, ΔAIC = 8.8) motor features predicted episodic memory performance relative to demographic and mood confounders only (R2 adj  = 8.1%). No tapping features improved estimation of working memory. DISCUSSION: Brief self-administered online hand movement tests predict asymptomatic episodic memory impairment. This provides a potential low-cost home-based method for stratification of enriched cohorts. HIGHLIGHTS: We devised two brief online keyboard tapping tests to assess hand motor function. 1169 cognitively asymptomatic adults completed motor- and cognitive tests online. Impaired hand motor function predicted reduced episodic memory performance. This brief self-administered test may aid stratification of community cohorts.

fNIRS as a biomarker for individuals with subjective memory complaints and MCI.

INTRODUCTION: Identifying individuals at risk of developing dementia is crucial for early intervention. Mild cognitive impairment (MCI) and subjective memory complaints (SMCs) are considered its preceding stages. This study aimed to assess the utility of functional near-infrared spectroscopy (fNIRS) in identifying individuals with MCI and SMC. METHODS: One hundred fifty-one participants were categorized into normal cognition (NC); amnestic MCI (aMCI); non-amnestic MCI (naMCI); and mild, moderate, and severe SMC groups. Task-related prefrontal hemodynamics were measured using fNIRS during a visual memory span task. RESULTS: Results showed significantly lower oxyhemoglobin (HbO) levels in aMCI, but not in naMCI, compared to the NC. In addition, severe SMC had lower HbO levels than the NC, mild, and moderate SMC. Receiver operating characteristic analysis demonstrated 69.23% and 69.70% accuracy in differentiating aMCI and severe SMC from NC, respectively. DISCUSSION: FNIRS may serve as a potential non-invasive biomarker for early detection of dementia. HIGHLIGHTS: Only amnestic mild cognitive impairment (aMCI), but not non-amnestic MCI, showed lower oxyhemoglobin (HbO) than normal individuals. Reduced HbO was observed in those with severe subjective memory complaints (SMCs) compared to normal cognition (NC), mild, and moderate SMCs. Functional near-infrared spectroscopy measures were associated with performance in memory assessments. Prefrontal hemodynamics could distinguish aMCI and severe SMC from NC.

Event-related potentials reveal visual episodic memory deficits in patients with temporal lobe epilepsy.

OBJECTIVE: Temporal lobe epilepsy (TLE) patients usually suffer from impaired episodic memory (EM), but its underlying electrophysiologic mechanism and impacted cognitive performance are unclear. We aim to investigate the association between episodic memory reserve and physiological measures of memory workload in TLE patients using Event-related potentials (ERP). METHODS: A change detection task with image stimuli assesses visual episodic memory. During the memory encoding and decoding phases, the ERP signals were analyzed from twenty-nine TLE patients (twelve with left TLE patients, seventeen with TLE), and thirty healthy controls. Given that EM is a complex process involving many fundamental cognitive processes, the amplitudes and latencies of EM-related ERP (FN400, late positive potential (LPC), and late posterior negativity (LPN)), and the ERP reflecting the fundamental processes (P100, N100, P200, and P300) were calculated. Then we used a three-by-two factorial design on the ERP metrics for interaction and main effects. The correlation analysis among Wechsler Memory Scales-Chinese Revision (WMS-RC) results, behavioral data, and the ERPs was carried out. RESULTS: The TLE patients performed worse in WMS-RC and the memory task. The increased P200 and decreased P300 amplitudes were observed in the TLE patients, and LPN was abnormal in only LTLE patients. For EM-related components, differences were observed in both the LTLE and RTLE patients: the lack of the FN400 effect, the lack of the reversed LPC effect, and the reduced FN400. No significant inter-group difference was detected for the latencies of all the ERPs. Additionally, there were significant correlations among WMS-RC scores, behaviors, and some ERP amplitudes. CONCLUSIONS: The impaired EM is linked to the increased P200 and decreased P300 amplitudes. LPN seems to be sensitive to left temporal lobe dysfunction. More importantly, the abnormal old or new effects of the FN400 and LPC, and the reduced FN400 amplitude might be associated with the visual EM deficit in the TLE patients. These findings may assist in the deep understanding of the EM disorder and the evaluation of the side effects of antiepileptic drugs.

Subjective memory complaints: Prevalence, associated factors and sex differences in the ELSI-Brazil study.

BACKGROUND: Subjective memory complaints (SMCs) are a possible prodrome of cognitive decline but are understudied in low- and middle-income countries (LMIC). We aimed to estimate the prevalence of SMCs in a large, nationally representative sample of older adults from Brazil and to identify sociodemographic and health-related factors that are associated with SMCs independently of objective memory. METHODS: Baseline data (n = 7831) from the ELSI-Brazil study, a national representative sample of adults aged 50 and over. They were asked to rate their memory and then divided into two groups - having or not having SMCs. Logistic regression models were used to estimate the association of demographic characteristics, health related factors, objective memory performance and disability in basic (b-ADL), instrumental (i-ADL), and advanced (a-ADL) activities of daily living associated with SMCs. Whether sex was an effect modifier of the association between age and objective memory performance and SMCs was also tested. RESULTS: Of the sample, 42% (95% CI; 39.9-43.9) had SMCs, and it was higher among women (46.9%) than men (35.9%). SMC prevalence decreased with age among women and increased among men, and for both it decreased with better cognitive performance. Fully adjusted logistic regression model showed that older age, higher education, higher b-ADL scores, and better cognitive performance were associated with decreased SMCs, while being female, with higher number of chronic conditions, higher i-ADL scores, worst self-rated health, and an increased number of depressive symptoms were associated with increased SMCs. However, the interaction test (p < 0.001) confirmed that increased age was associated with decreased SMCs only among women, and that better objective memory performance was associated with decreased SMCs only among men. CONCLUSIONS: SMCs are common in the Brazilian older population and are associated with health and sociodemographic factors, with different patterns between men and women. There is a need for future studies looking at the cognitive trajectory and dementia risk in older adults with subjective cognitive complaints.

Individual differences in frequency and impact of daily memory lapses: results from a national lifespan sample.

BACKGROUND: Everyday memory problems are believed to increase with age, leading many researchers to focus on older ages when examining reports of memory lapses. However, real world memory lapses are ubiquitous across the adult lifespan, though less is known about the types of problems and their impacts at younger ages. The current study examined occurrence and impacts of memory lapses using daily diaries in a broad age range and whether characteristics of lapses varied across age, gender, or education level. METHODS: Using an 8-day daily diary protocol, 2,018 individuals (ages 25-91) provided reports of their experiences of two types of daily memory lapses (retrospective and prospective) as well as the impact those lapses had on their emotional and functional well-being that day. Using multilevel modeling, we examined the likelihood of reporting memory lapses and their impacts on daily life and whether these depended on age, gender, or education level. RESULTS: Participants reported lapses on approximately 40% of days; retrospective memory lapses were significantly more likely than prospective lapses. Older ages and higher education level were related to greater likelihood of reporting retrospective lapses. Women (compared to men) were more likely to report prospective memory lapses. Women also tended to report greater impacts of their memory lapses. Lower education levels were related to greater impacts of memory lapses compared to higher education levels. Interestingly, age was not related to impacts of lapses. DISCUSSION: Our results indicate that memory lapses are common across the lifespan and that those individuals more likely to report lapses are not necessarily those that experience the greatest impacts of those lapses on daily life. Additional work is needed to understand the daily experience of memory lapses and how they differentially affect individuals regardless of age, gender, and education. CONCLUSIONS: Memory lapses are an important aspect of daily life across the lifespan and require measurement in an individual's real-world environments. Better measurement of these experiences will allow the development of more sensitive measures of changes in cognitive functioning that may impact an individual's ability to live independently.

A qualitative exploration of older people's lived experiences of homelessness and memory problems - stakeholder perspectives.

BACKGROUND: The numbers of older people experiencing both homelessness and memory problems are growing, yet their complex health, housing and care needs remain undelineated and unmet. There is a critical gap in understanding what can improve the care, support and experiences of this group. In this qualitative study we explore how stakeholders understand memory problems among older people in the context of homelessness and consider what they judge gets in the way of achieving positive outcomes. METHOD: We conducted reflexive thematic analysis of qualitative interviews (n = 49) using a semi-structured topic guide, with 17 older people (aged ≥ 50 years) experiencing memory problems and homelessness, 15 hostel staff and managers, and 17 health, housing and social care practitioners. We recruited participants from six homelessness hostels, one specialist care home and National Health and Local Authority Services in England. RESULTS: We identified four overarching themes. The population is not taken seriously; multiple causes are hard to disentangle; risk of exploitation and vulnerability; and (dis)connection and social isolation. The transience and lack of stability associated with homelessness intensified the disorienting nature of memory and cognitive impairment, and those providing direct and indirect support required flexibility and persistence, with staff moving beyond traditional roles to advocate, provide care and safeguard individuals. Memory problems were perceived by frontline staff and older people to be overlooked, misinterpreted, and misattributed as being caused by alcohol use, resulting in pervasive barriers to achieving positive and desired outcomes. CONCLUSIONS: Efforts to meet the needs of older people living with memory problems and experiencing homelessness and future interventions must reflect the complexity of their lives, often in the context of long-term alcohol use and current service provision and we make suggestions as to what could be done to improve the situation.

Association of Sleep Disturbance With Neurocognition, Symptom Severity, and Recovery in Pediatric Concussion: A 10-Year Retrospective Analysis of a Tertiary Referral Concussion Clinic.

OBJECTIVES: To investigate the relationship between sleep disturbance, neurocognition, symptom severity, and recovery in children and adolescents with concussion. Sex-related comparisons were also examined. SETTING: Pediatric tertiary referral concussion clinic. PARTICIPANTS: Children and adolescents (aged 6-18 years; n = 554) diagnosed with concussion. DESIGN: Cross-sectional retrospective study. MAIN MEASURES: Assessment data were obtained from Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) Applications. Sleep disturbance was quantified using the sleep-related domains of the Post-Concussion Symptom Scale (PCSS) and self-report sleep duration. Sleep duration was categorized as short (<7 hours), intermediate (7-9 hours), and long (≥9 hours). Outcome measures included neurocognition, measured via composite scores of ImPACT cognitive domains (verbal memory, visual memory, visual motor speed, reaction time); symptom severity, using the PCSS; and concussion recovery time (days). RESULTS: Short sleep resulted in significantly poorer verbal memory ( P = .03), visual memory ( P = .02), and reaction time ( P = .01). Sleep disturbance was strongly associated with total symptom burden (ρ = 0.90, P < .001). Recovery time, median (interquartile range), was significantly prolonged with short sleep, 61 (30-136) days, compared with intermediate, 38 (21-72) days, and long, 34 (19-71) days, sleep ( P < .001). Overall, female participants demonstrated significantly longer recovery times than male participants (mean 91 ± 95 vs 58 ± 85 days, P < .001). Females exhibited similar concussion recovery times irrespective of reported sleep duration ( P = .95), whereas mean recovery time in males was significantly longer with short sleep (84 ± 82 days) than with intermediate (61 ± 106 days) and long (49 ± 62 days) sleep ( P < .001). CONCLUSION: Sleep disturbance following concussion poses as a promising modifiable risk factor to alleviate postinjury impairments, including cognitive deficits and symptom burden. Female children were found to experience more severe concussion symptoms and protracted recovery times than their male counterparts. Investigations into the factors that may contribute to sex-related differences following concussion are warranted.

Influence of amyloid and diagnostic syndrome on non-traditional memory scores in early-onset Alzheimer's disease.

INTRODUCTION: The Rey Auditory Verbal Learning Test (RAVLT) is a useful neuropsychological test for describing episodic memory impairment in dementia. However, there is limited research on its utility in early-onset Alzheimer's disease (EOAD). We assess the influence of amyloid and diagnostic syndrome on several memory scores in EOAD. METHODS: We transcribed RAVLT recordings from 303 subjects in the Longitudinal Early-Onset Alzheimer's Disease Study. Subjects were grouped by amyloid status and syndrome. Primacy, recency, J-curve, duration, stopping time, and speed score were calculated and entered into linear mixed effects models as dependent variables. RESULTS: Compared with amyloid negative subjects, positive subjects exhibited effects on raw score, primacy, recency, and stopping time. Inter-syndromic differences were noted with raw score, primacy, recency, J-curve, and stopping time. DISCUSSION: RAVLT measures are sensitive to the effects of amyloid and syndrome in EOAD. Future work is needed to quantify the predictive value of these scores. HIGHLIGHTS: RAVLT patterns characterize various presentations of EOAD and EOnonAD Amyloid impacts raw score, primacy, recency, and stopping time Timing-based scores add value over traditional count-based scores.

The Architecture of Human Memory: Insights from Human Single-Neuron Recordings.

Deciphering the mechanisms of human memory is a central goal of neuroscience, both from the point of view of the fundamental biology of memory and for its translational relevance. Here, we review some contributions that recordings from neurons in humans implanted with electrodes for clinical purposes have made toward this goal. Recordings from the medial temporal lobe, including the hippocampus, reveal the existence of two classes of cells: those encoding highly selective and invariant representations of abstract concepts, and memory-selective cells whose activity is related to familiarity and episodic retrieval. Insights derived from observing these cells in behaving humans include that semantic representations are activated before episodic representations, that memory content and memory strength are segregated, and that the activity of both types of cells is related to subjective awareness as expected from a substrate for declarative memory. Visually selective cells can remain persistently active for several seconds, thereby revealing a cellular substrate for working memory in humans. An overarching insight is that the neural code of human memory is interpretable at the single-neuron level. Jointly, intracranial recording studies are starting to reveal aspects of the building blocks of human memory at the single-cell level. This work establishes a bridge to cellular-level work in animals on the one hand, and the extensive literature on noninvasive imaging in humans on the other hand. More broadly, this work is a step toward a detailed mechanistic understanding of human memory that is needed to develop therapies for human memory disorders.

Accelerated long-term forgetting in adult patients with genetic generalized epilepsy.

OBJECTIVE: Accelerated long-term forgetting (ALF) has been demonstrated among children but not adults with genetic generalized epilepsy (GGE). We investigated (1) how forgetting patterns of verbal and visuospatial material differ between patients with GGE and healthy controls (HCs) and (2) whether ALF is associated with ictal or interictal epileptic activity. METHODS: Forty-two patients with GGE (39, 92.9% experiencing seizures) were compared to 57 HCs in word, logical story, and Rey-Osterrieth complex figure recall tasks by testing after intervals of 30 min and 4 weeks. Ambulatory electroencephalography (EEG) was performed before testing to detect generalized epileptic activity, and patients were asked to document the number of seizures during the 4-week interval. RESULTS: A two-way repeated measures ANOVA indicated that individuals with GGE have different forgetting patterns in comparison to HCs in tasks of word (delay by group interaction F1.5, 142.5  = 4.5, p = .02, ηp2  = .04) and figure (F2, 194  = 15.9, p < .001, ηp2  = .14) but not story (F1.6 151.1  = .5, p = .58, ηp2  = .005) recall. Last learning trial-adjusted scores of word recall were comparable between HCs and patients with epilepsy (PWEs) at 30 min (p = .21) but not at 4 weeks (p = .006). Individuals with GGE performed worse than HCs in figure recall at 30 min and 4 weeks (p < .001), with lower performance after the 4-week interval present only among seizure-positive and EEG-positive individuals (p < .001) during subgroup analysis. Performance on memory tests was unrelated to overall seizure frequency, the number of antiseizure drugs used, and epilepsy duration. SIGNIFICANCE: Our study supports the presence of ALF in a task of word recall among adult patients with GGE. The pattern of forgetting visuospatial information suggests greater forgetting of material before the first delay and ongoing deficits among PWEs with epileptic activity. Future studies should confirm our findings and investigate the functional or pathological mechanisms of memory dysfunction in GGE.

"Do I Have a Memory Problem? I Can't Recall": An Evaluation of Measurement Invariance in Subjective Reporting of Memory Symptoms among Persons with and without Objective HIV-Associated Memory Impairment.

OBJECTIVE: Memory symptoms and objective impairment are common in HIV disease and are associated with disability. A paradoxical issue is that objective episodic memory failures can interfere with accurate recall of memory symptoms. The present study assessed whether responses on a self-report scale of memory symptoms demonstrate measurement invariance in persons with and without objective HIV-associated memory impairment. METHOD: In total, 505 persons with HIV completed the Prospective and Retrospective Memory Questionnaire (PRMQ). Objective memory impairment (n = 141) was determined using a 1-SD cutoff on clinical tests of episodic memory. PRMQ measurement invariance was assessed by confirmatory factor analyses examining a one-factor model with increasing cross-group equality constraints imposed on factor loadings and item thresholds (i.e., configural, weak, and strong invariance). RESULTS: Configural model fit indicated that identical items measured a one-factor model for both groups. Comparison to the weak model indicated that factor loadings were equivalent across groups. However, there was evidence of partial strong invariance, with two PRMQ item thresholds differing across memory impairment groups. Post hoc analyses using a 1.5-SD memory impairment cutoff (n = 77) revealed both partial weak and partial strong invariance, such that PRMQ item loadings differed across memory groups for three items. CONCLUSIONS: The PRMQ demonstrated a robust factor structure among persons with and without objective HIV-associated memory impairment. However, on select PRMQ items, individuals with memory impairment reported observed scores that were relatively higher than their latent score, while items were more strongly associated with the memory factor in a group with greater memory impairment.