Neuropsychiatric symptom burden in early-onset and late-onset Alzheimer's disease as a function of age.

INTRODUCTION: We examined the burden of neuropsychiatric symptoms (NPSs) in early-onset (EO) and late-onset (LO) Alzheimer's disease (AD) and adjusted for age effects via the inclusion of cognitively unimpaired (CU) individuals. METHODS: Cross-sectional data from 2940 EOAD, 8665 LOAD, and 8775 age-stratified CU individuals (early-CU, n = 2433; late-CU, n = 6342) from the National Alzheimer's Coordinating Center database were included. Fisher's exact tests compared EOAD and LOAD on the presence and severity of NPSs. Multiple logistic regression models included an age*diagnosis interaction to examine age effects. RESULTS: Presence (ps < 0.0001) and severity (ps < 0.05) of NPS were greater in EOAD than in LOAD. However, after adjusting for base rates in NPS in CU individuals (age effects), only elation and eating behaviors were more frequent in EOAD (ps < 0.05) and nighttime behaviors more frequent and severe in LOAD (ps < 0.05). DISCUSSION: Few NPSs were specific to the EOAD versus LOAD. Previous findings of greater NPS burden in EOAD may partially reflect age effects. HIGHLIGHTS: Adjusting for age effect, elation and eating problems are more frequent in EOAD. Adjusting for age effect, sleep disturbances are more frequent and severe in LOAD. Age effects underlie higher neuropsychiatric symptom presentation in EOAD than in LOAD.

Performance on the African neuropsychology battery using the learning ratio in a sample of healthy Congolese.

OBJECTIVE: Using the African Neuropsychology Battery (ANB), we seek to develop normative data by examining the demographic effects for two learning process scores: initial learning (Trial One) and learning ratio (LR, the percentage of items learned relative of to-be-learned material following Trial 1). METHODS: Healthy participants from the Democratic Republic of Congo completed the four memory tests of the ANB: the African Story Memory Test (ASMT), African List Memory Test (ALMT), African Visuospatial Memory Test (AVMT), and African Contextual Visuospatial Memory Test (ACVMT). We developed indices of learning for each subtest, as well as aggregate learning indices for Trial 1 and LR, and composite indices examining verbal, visual, contextual, and noncontextual learning, and grand indices comprising all four subtests. RESULTS: Trial 1 and LR scores each demonstrated acceptable intercorrelations across memory tests. We present normative data for Trial 1 and LR by age and education. CONCLUSION: These data provide normative standards for evaluating learning in Sub-Saharan Africa.

Exploring factors contributing to caregiver burden in family caregivers of congolese adults with suspected dementia.

INTRODUCTION: Predicting caregiver burden in individuals with suspected dementia - is critical due to the debilitating nature of these disorders and need for caregiver support. While some examination of the factors affecting burden has been undertaken in Sub-Saharan Africa, each country presents with its own unique challenges and obstacles. This pilot study investigates predictors of caregiver burden in family caregivers of individuals with suspected dementia living in the Democratic Republic of the Congo (DRC). METHODS: Linear and multiple regression analyses were conducted to explore factors associated with caregiver burden in 30 patient-caregiver dyads with the Zarit Burden Interview (ZBI) for caregiver burden evaluation. Cognitive impairments of patients were assessed using the Community Screening Instrument for Dementia, Alzheimer's Questionnaire (AQ), the African Neuropsychology Battery, and the Neuropsychiatric Symptoms Inventory (NPI). RESULTS: Average caregiver burden on the ZBI was 36.1 (SD = 14.6; range = 12-58). Greater impairments in patient cognition (orientation, visuospatial, memory, executive functioning), fragility, and neuropsychiatric symptoms (delirium, agitation, depression) were predictive of caregiver burden. After controlling for AQ scores and caregiver gender, greater symptoms of depression, and worse performances on verbal memory and problem solving were associated with greater caregiver burden. CONCLUSION: Worsening patient fragility, cognition, functioning, and neuropsychiatric symptoms influenced caregiver burden in caregivers of individuals with suspected cognitive impairment in the DRC. These findings are consistent with the prior literature. Future studies may wish to explore supportive factors and caregiver specific characteristics that buffer against perceived burden.

Prevalence of suspected dementia in a sample of adults living in Kinshasa-Democratic Republic of the Congo.

BACKGROUND: The prevalence of dementia in Sub-Saharan Africa, particularly in French-speaking countries, has received limited attention. This study investigates the prevalence and risk factors of suspected dementia in elderly adults in Kinshasa, Democratic Republic of the Congo (DRC). METHODS: A community-based sample of 355 individuals over 65 years old was selected using multistage probability sampling in Kinshasa. Participants were screened using the Community Screening Instrument for Dementia, Alzheimer's Questionnaire, Geriatric Depression Scale, Beck Anxiety Inventory, and Individual Fragility Questionnaire, followed by clinical interview and neurological examination. Suspected dementia diagnoses were made based on the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria including significant cognitive and functional impairments. Prevalence and odds ratios (ORs) with 95% confidence interval (CI) were calculated using, respectively, regression and logistic regression. RESULTS: Among 355 participants (mean age 74, SD = 7; 51% male), the crude prevalence of suspected dementia was 6.2% (9.0% in women and 3.8% in men). Female sex was a significant factor associated with suspected dementia [OR = 2.81, 95% CI (1.08-7.41)]. The prevalence of dementia increased with age (14.0% after 75 years and 23.1% after 85 years), with age being significantly associated with suspected dementia [OR = 5.42, 95% CI (2.86-10.28)]. Greater education was associated with a lower prevalence of suspected dementia [OR = 2.36, 95% CI (2.14-2.94), comparing those with ≥7.3 years of education to those with <7.3 years of education]. Other factors associated with the prevalence of suspected dementia included being widowed (OR = 1.66, 95% CI (1.05-2.61), being retired or semi-retired (OR = 3.25, 95% CI (1.50-7.03)], a diagnosis of anxiety [OR = 2.56, 95% CI (1.05-6.13)], and death of a spouse or a relative after age 65 [OR = 1.73, 95% CI (1.58-1.92)]. In contrast, depression [OR = 1.92, 95% CI (0.81-4.57)], hypertension [OR = 1.16, 95% CI (0.79-1.71)], body mass index (BMI) [OR = 1.06, 95% CI (0.40-2.79)], and alcohol consumption [OR = 0.83, 95% CI (0.19-3.58)] were not significantly associated with suspected dementia. CONCLUSIONS: This study found a prevalence of suspected dementia in Kinshasa/DRC similar to other developing countries and Central African countries. Reported risk factors provide information to identify high-risk individuals and develop preventive strategies in this setting.

Developments in understanding early onset Alzheimer's disease.

On September 25 and 26, 2021, the Alzheimer's Association hosted the first meeting focused on people with early-onset Alzheimer's disease (EOAD)-sometimes referred to as younger onset Alzheimer's disease (AD). Though a diagnosis of AD can be devastating at any age, those with a younger onset-defined as symptoms developing prior to 65 years of age-face unique challenges. EOAD occurs when people are in the prime of their lives, often with multiple responsibilities including careers, community activities, and raising children and caring for older family members. These challenges warrant special consideration and study, yet people with EOAD are often excluded from AD research because of their atypical age of onset. To help fill this gap, we designed and launched the Longitudinal Early-Onset Alzheimer's Disease Study (LEADS) to enroll and follow 500 people with EOAD from > 15 sites in the United States, which the National Institute on Aging funded in 2018. The September 2021 meeting was designed to inform people with EOAD and their family members and caregivers about the latest research on the biology of EOAD, treatments in the pipeline, practical considerations about legal and financial arrangements for families, and the support networks available to them. More than 217 registrants attended.

A simulative deep learning model of SNP interactions on chromosome 19 for predicting Alzheimer's disease risk and rates of disease progression.

BACKGROUND: Identifying genetic patterns that contribute to Alzheimer's disease (AD) is important not only for pre-symptomatic risk assessment but also for building personalized therapeutic strategies. METHODS: We implemented a novel simulative deep learning model to chromosome 19 genetic data from the Alzheimer's Disease Neuroimaging Initiative and the Imaging and Genetic Biomarkers of Alzheimer's Disease datasets. The model quantified the contribution of each single nucleotide polymorphism (SNP) and their epistatic impact on the likelihood of AD using the occlusion method. The top 35 AD-risk SNPs in chromosome 19 were identified, and their ability to predict the rate of AD progression was analyzed. RESULTS: Rs561311966 (APOC1) and rs2229918 (ERCC1/CD3EAP) were recognized as the most powerful factors influencing AD risk. The top 35 chromosome 19 AD-risk SNPs were significant predictors of AD progression. DISCUSSION: The model successfully estimated the contribution of AD-risk SNPs that account for AD progression at the individual level. This can help in building preventive precision medicine.

Learning slopes in early-onset Alzheimer's disease.

OBJECTIVE: Investigation of learning slopes in early-onset dementias has been limited. The current study aimed to highlight the sensitivity of learning slopes to discriminate disease severity in cognitively normal participants and those diagnosed with early-onset dementia with and without ß-amyloid positivity METHOD: Data from 310 participants in the Longitudinal Early-Onset Alzheimer's Disease Study (aged 41 to 65) were used to calculate learning slope metrics. Learning slopes among diagnostic groups were compared, and the relationships of slopes with standard memory measures were determined RESULTS: Worse learning slopes were associated with more severe disease states, even after controlling for demographics, total learning, and cognitive severity. A particular metric-the learning ratio (LR)-outperformed other learning slope calculations across analyses CONCLUSIONS: Learning slopes appear to be sensitive to early-onset dementias, even when controlling for the effect of total learning and cognitive severity. The LR may be the learning measure of choice for such analyses. HIGHLIGHTS: Learning is impaired in amyloid-positive EOAD, beyond cognitive severity scores alone. Amyloid-positive EOAD participants perform worse on learning slopes than amyloid-negative participants. Learning ratio appears to be the learning metric of choice for EOAD participants.

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.

Sex and APOE ε4 carrier effects on atrophy, amyloid PET, and tau PET burden in early-onset Alzheimer's disease.

INTRODUCTION: We used sex and apolipoprotein E ε4 (APOE ε4) carrier status as predictors of pathologic burden in early-onset Alzheimer's disease (EOAD). METHODS: We included baseline data from 77 cognitively normal (CN), 230 EOAD, and 70 EO non-Alzheimer's disease (EOnonAD) participants from the Longitudinal Early-Onset Alzheimer's Disease Study (LEADS). We stratified each diagnostic group by males and females, then further subdivided each sex by APOE ε4 carrier status and compared imaging biomarkers in each stratification. Voxel-wise multiple linear regressions yielded statistical brain maps of gray matter density, amyloid, and tau PET burden. RESULTS: EOAD females had greater amyloid and tau PET burdens than males. EOAD female APOE ε4 non-carriers had greater amyloid PET burdens and greater gray matter atrophy than female ε4 carriers. EOnonAD female ε4 non-carriers also had greater gray matter atrophy than female ε4 carriers. DISCUSSION: The effects of sex and APOE ε4 must be considered when studying these populations. HIGHLIGHTS: Novel analysis examining the effects of biological sex and apolipoprotein E ε4 (APOE Îµ4) carrier status on neuroimaging biomarkers among early-onset Alzheimer's disease (EOAD), early-onset non-AD (EOnonAD), and cognitively normal (CN) participants. Female sex is associated with greater pathology burden in the EOAD cohort compared to male sex. The effect of APOE ε4 carrier status on pathology burden was the most impactful in females across all cohorts.

White matter hyperintensities are higher among early-onset Alzheimer's disease participants than their cognitively normal and early-onset nonAD peers: Longitudinal Early-onset Alzheimer's Disease Study (LEADS).

INTRODUCTION: We compared white matter hyperintensities (WMHs) in early-onset Alzheimer's disease (EOAD) with cognitively normal (CN) and early-onset amyloid-negative cognitively impaired (EOnonAD) groups in the Longitudinal Early-Onset Alzheimer's Disease Study. METHODS: We investigated the role of increased WMH in cognition and amyloid and tau burden. We compared WMH burden of 205 EOAD, 68 EOnonAD, and 89 CN participants in lobar regions using t-tests and analyses of covariance. Linear regression analyses were used to investigate the association between WMH and cognitive impairment and that between amyloid and tau burden. RESULTS: EOAD showed greater WMHs compared with CN and EOnonAD participants across all regions with no significant differences between CN and EOnonAD groups. Greater WMHs were associated with worse cognition. Tau burden was positively associated with WMH burden in the EOAD group. DISCUSSION: EOAD consistently showed higher WMH volumes. Overall, greater WMHs were associated with worse cognition and higher tau burden in EOAD. HIGHLIGHTS: This study represents a comprehensive characterization of WMHs in sporadic EOAD. WMH volumes are associated with tau burden from positron emission tomography (PET) in EOAD, suggesting WMHs are correlated with increasing burden of AD. Greater WMH volumes are associated with worse performance on global cognitive tests. EOAD participants have higher WMH volumes compared with CN and early-onset amyloid-negative cognitively impaired (EOnonAD) groups across all brain regions.

Cerebrospinal fluid biomarkers in the Longitudinal Early-onset Alzheimer's Disease Study.

INTRODUCTION: One goal of the Longitudinal Early Onset Alzheimer's Disease Study (LEADS) is to define the fluid biomarker characteristics of early-onset Alzheimer's disease (EOAD). METHODS: Cerebrospinal fluid (CSF) concentrations of Aß1-40, Aß1-42, total tau (tTau), pTau181, VILIP-1, SNAP-25, neurogranin (Ng), neurofilament light chain (NfL), and YKL-40 were measured by immunoassay in 165 LEADS participants. The associations of biomarker concentrations with diagnostic group and standard cognitive tests were evaluated. RESULTS: Biomarkers were correlated with one another. Levels of CSF Aß42/40, pTau181, tTau, SNAP-25, and Ng in EOAD differed significantly from cognitively normal and early-onset non-AD dementia; NfL, YKL-40, and VILIP-1 did not. Across groups, all biomarkers except SNAP-25 were correlated with cognition. Within the EOAD group, Aß42/40, NfL, Ng, and SNAP-25 were correlated with at least one cognitive measure. DISCUSSION: This study provides a comprehensive analysis of CSF biomarkers in sporadic EOAD that can inform EOAD clinical trial design.

Amyloid and tau-PET in early-onset AD: Baseline data from the Longitudinal Early-onset Alzheimer's Disease Study (LEADS).

INTRODUCTION: We aimed to describe baseline amyloid-beta (Aß) and tau-positron emission tomograrphy (PET) from Longitudinal Early-onset Alzheimer's Disease Study (LEADS), a prospective multi-site observational study of sporadic early-onset Alzheimer's disease (EOAD). METHODS: We analyzed baseline [18F]Florbetaben (Aß) and [18F]Flortaucipir (tau)-PET from cognitively impaired participants with a clinical diagnosis of mild cognitive impairment (MCI) or AD dementia aged < 65 years. Florbetaben scans were used to distinguish cognitively impaired participants with EOAD (Aß+) from EOnonAD (Aß-) based on the combination of visual read by expert reader and image quantification. RESULTS: 243/321 (75.7%) of participants were assigned to the EOAD group based on amyloid-PET; 231 (95.1%) of them were tau-PET positive (A+T+). Tau-PET signal was elevated across cortical regions with a parietal-predominant pattern, and higher burden was observed in younger and female EOAD participants. DISCUSSION: LEADS data emphasizes the importance of biomarkers to enhance diagnostic accuracy in EOAD. The advanced tau-PET binding at baseline might have implications for therapeutic strategies in patients with EOAD. HIGHLIGHTS: 72% of patients with clinical EOAD were positive on both amyloid- and tau-PET. Amyloid-positive patients with EOAD had high tau-PET signal across cortical regions. In EOAD, tau-PET mediated the relationship between amyloid-PET and MMSE. Among EOAD patients, younger onset and female sex were associated with higher tau-PET.

Baseline neuropsychiatric symptoms and psychotropic medication use midway through data collection of the Longitudinal Early-Onset Alzheimer's Disease Study (LEADS) cohort.

INTRODUCTION: We examined neuropsychiatric symptoms (NPS) and psychotropic medication use in a large sample of individuals with early-onset Alzheimer's disease (EOAD; onset 40-64 years) at the midway point of data collection for the Longitudinal Early-onset Alzheimer's Disease Study (LEADS). METHODS: Baseline NPS (Neuropsychiatric Inventory - Questionnaire; Geriatric Depression Scale) and psychotropic medication use from 282 participants enrolled in LEADS were compared across diagnostic groups - amyloid-positive EOAD (n = 212) and amyloid negative early-onset non-Alzheimer's disease (EOnonAD; n = 70). RESULTS: Affective behaviors were the most common NPS in EOAD at similar frequencies to EOnonAD. Tension and impulse control behaviors were more common in EOnonAD. A minority of participants were using psychotropic medications, and use was higher in EOnonAD. DISCUSSION: Overall NPS burden and psychotropic medication use were higher in EOnonAD than EOAD participants. Future research will investigate moderators and etiological drivers of NPS, and NPS differences in EOAD versus late-onset AD.

Profiling baseline performance on the Longitudinal Early-Onset Alzheimer's Disease Study (LEADS) cohort near the midpoint of data collection.

OBJECTIVE: The Longitudinal Early-Onset Alzheimer's Disease Study (LEADS) seeks to provide comprehensive understanding of early-onset Alzheimer's disease (EOAD; onset <65 years), with the current study profiling baseline clinical, cognitive, biomarker, and genetic characteristics of the cohort nearing the data-collection mid-point. METHODS: Data from 371 LEADS participants were compared based on diagnostic group classification (cognitively normal [n = 89], amyloid-positive EOAD [n = 212], and amyloid-negative early-onset non-Alzheimer's disease [EOnonAD; n = 70]). RESULTS: Cognitive performance was worse for EOAD than other groups, and EOAD participants were apolipoprotein E (APOE) ε4 homozygotes at higher rates. An amnestic presentation was common among impaired participants (81%), with several clinical phenotypes present. LEADS participants generally consented at high rates to optional trial procedures. CONCLUSIONS: We present the most comprehensive baseline characterization of sporadic EOAD in the United States to date. EOAD presents with widespread cognitive impairment within and across clinical phenotypes, with differences in APOE ε4 allele carrier status appearing to be relevant. HIGHLIGHTS: Findings represent the most comprehensive baseline characterization of sporadic early-onset Alzheimer's disease (EOAD) to date. Cognitive impairment was widespread for EOAD participants and more severe than other groups. EOAD participants were homozygous apolipoprotein E (APOE) ε4 carriers at higher rates than the EOnonAD group. Amnestic presentation predominated in EOAD and EOnonAD participants, but other clinical phenotypes were present.

Pathogenic variants in the Longitudinal Early-onset Alzheimer's Disease Study cohort.

INTRODUCTION: One goal of the Longitudinal Early-onset Alzheimer's Disease Study (LEADS) is to investigate the genetic etiology of early onset (40-64 years) cognitive impairment. Toward this goal, LEADS participants are screened for known pathogenic variants. METHODS: LEADS amyloid-positive early-onset Alzheimer's disease (EOAD) or negative early-onset non-AD (EOnonAD) cases were whole exome sequenced (N = 299). Pathogenic variant frequency in APP, PSEN1, PSEN2, GRN, MAPT, and C9ORF72 was assessed for EOAD and EOnonAD. Gene burden testing was performed in cases compared to similar-age cognitively normal controls in the Parkinson's Progression Markers Initiative (PPMI) study. RESULTS: Previously reported pathogenic variants in the six genes were identified in 1.35% of EOAD (3/223) and 6.58% of EOnonAD (5/76). No genes showed enrichment for carriers of rare functional variants in LEADS cases. DISCUSSION: Results suggest that LEADS is enriched for novel genetic causative variants, as previously reported variants are not observed in most cases. HIGHLIGHTS: Sequencing identified eight cognitively impaired pathogenic variant carriers. Pathogenic variants were identified in PSEN1, GRN, MAPT, and C9ORF72. Rare variants were not enriched in APP, PSEN1/2, GRN, and MAPT. The Longitudinal Early-onset Alzheimer's Disease Study (LEADS) is a key resource for early-onset Alzheimer's genetic research.

The Sporadic Early-onset Alzheimer's Disease Signature Of Atrophy: Preliminary Findings From The Longitudinal Early-onset Alzheimer's Disease Study (LEADS) Cohort.

INTRODUCTION: Magnetic resonance imaging (MRI) research has advanced our understanding of neurodegeneration in sporadic early-onset Alzheimer's disease (EOAD) but studies include small samples, mostly amnestic EOAD, and have not focused on developing an MRI biomarker. METHODS: We analyzed MRI scans to define the sporadic EOAD-signature atrophy in a small sample (n = 25) of Massachusetts General Hospital (MGH) EOAD patients, investigated its reproducibility in the large longitudinal early-onset Alzheimer's disease study (LEADS) sample (n = 211), and investigated the relationship of the magnitude of atrophy with cognitive impairment. RESULTS: The EOAD-signature atrophy was replicated across the two cohorts, with prominent atrophy in the caudal lateral temporal cortex, inferior parietal lobule, and posterior cingulate and precuneus cortices, and with relative sparing of the medial temporal lobe. The magnitude of EOAD-signature atrophy was associated with the severity of cognitive impairment. DISCUSSION: The EOAD-signature atrophy is a reliable and clinically valid biomarker of AD-related neurodegeneration that could be used in clinical trials for EOAD. HIGHLIGHTS: We developed an early-onset Alzheimer's disease (EOAD)-signature of atrophy based on magnetic resonance imaging (MRI) scans. EOAD signature was robustly reproducible across two independent patient cohorts. EOAD signature included prominent atrophy in parietal and posterior temporal cortex. The EOAD-signature atrophy was associated with the severity of cognitive impairment. EOAD signature is a reliable and clinically valid biomarker of neurodegeneration.

Computerized Cognitive Training in Amnestic Mild Cognitive Impairment: A Randomized Clinical Trial.

OBJECTIVE: Computerized cognitive training has been successful in healthy older adults, but its efficacy has been mixed in patients with amnestic Mild Cognitive Impairment (MCI). METHODS: In a randomized, placebo-controlled, double-blind, parallel clinical trial, we examined the short- and long-term efficacy of a brain-plasticity computerized cognitive training in 113 participants with amnestic MCI. RESULTS: Immediately after 40-hours of training, participants in the active control group who played computer games performed better than those in the experimental group on the primary cognitive outcome (p = 0.02), which was an auditory memory/attention composite score. There were no group differences on 2 secondary outcomes (global cognitive composite and rating of daily functioning). After 1 year, there was no difference between the 2 groups on primary or secondary outcomes. No adverse events were noted. CONCLUSIONS: Although the experimental cognitive training program did not improve outcomes in those with MCI, the short-term effects of the control group should not be dismissed, which may alter treatment recommendations for these patients.

Predicting daily functioning with the modified Telephone Interview for Cognitive Status.

BACKGROUND: The modified Telephone Interview for Cognitive Status (mTICS) is a frequently used telephone-based cognitive screening measure that can distinguish between normal aging, mild cognitive impairment (MCI), and dementia. Although it has been used to predict current and future cognitive function in older adults, no studies have examined if the mTICS can predict daily functioning. AIMS: The current study sought to examine the relationship between the mTICS and a performance-based measure of daily functioning. METHODS: The mTICS and demographic information (age, sex, education) were collected during a telephone screening visit for 149 older adults (65-91 years in age) with amnestic MCI. Three subscales of the Independent Living Scales (ILS; Managing Money, Managing Home and Transportation, Health and Safety) were collected during a baseline visit and during a 16 month follow-up visit in a subsample of 93 individuals. RESULTS: Using simple hierarchical regression, baseline mTICS total score combined with demographic variables significantly predicted 19-22% of baseline ILS subscale scores. Similarly, in a subsample of 93 participants with 16 month follow-up data, baseline mTICS and demographic information predicted 9-31% of ILS subscale scores at follow-up. CONCLUSIONS: The mTICS appears able to predict daily functioning in older individuals with MCI. Remote tracking of cognition and daily functioning in this at-risk group seems particularly beneficial to geriatricians and other providers, especially during COVID-19.

Preliminary Validation of the Learning Ratio for the HVLT-R and BVMT-R in Older Adults.

BACKGROUND: The learning slope is typically represented as the raw difference between the final score and the score of the first learning trial. A new method for calculating the learning slope, the learning ratio (LR), was recently developed; it is typically represented as the number of items that are learned after the first trial divided by the number of items that are yet to be learned. OBJECTIVE: To evaluate the convergent and criterion validity of the LR in order to understand its sensitivity to Alzheimer disease (AD) pathology. METHOD: Fifty-six patients from a memory clinic underwent standard neuropsychological assessment and quantitative brain imaging. LR scores were calculated from the Hopkins Verbal Learning Test-Revised and the Brief Visuospatial Memory Test-Revised and were compared with both standard memory measures and total hippocampal volumes, as well as between individuals with AD and those with mild cognitive impairment. RESULTS: Lower LR scores were consistently associated with poorer performances on standard memory measures and smaller total hippocampal volumes, generally more so than traditional learning slope scores. The LR scores of the AD group were smaller than those of the group with mild cognitive impairment. Furthermore, the aggregation of LR scores into a single metric was partially supported. CONCLUSION: The LR is sensitive to AD pathology along the AD continuum. This result supports previous claims that the LR score can reflect learning capacity better than traditional learning calculations can by considering the amount of information that is learned at trial 1.

Short-Term Practice Effects on Cognitive Tests Across the Late Life Cognitive Spectrum and How They Compare to Biomarkers of Alzheimer's Disease.

Background: Practice effects on cognitive testing in mild cognitive impairment (MCI) and Alzheimer's disease (AD) remain understudied, especially with how they compare to biomarkers of AD. Objective: The current study sought to add to this growing literature. Methods: Cognitively intact older adults (n = 68), those with amnestic MCI (n = 52), and those with mild AD (n = 45) completed a brief battery of cognitive tests at baseline and again after one week, and they also completed a baseline amyloid PET scan, a baseline MRI, and a baseline blood draw to obtain APOE ɛ4 status. Results: The intact participants showed significantly larger baseline cognitive scores and practice effects than the other two groups on overall composite measures. Those with MCI showed significantly larger baseline scores and practice effects than AD participants on the composite. For amyloid deposition, the intact participants had significantly less tracer uptake, whereas MCI and AD participants were comparable. For total hippocampal volumes, all three groups were significantly different in the expected direction (intact > MCI > AD). For APOE ɛ4, the intact had significantly fewer copies of ɛ4 than MCI and AD. The effect sizes of the baseline cognitive scores and practice effects were comparable, and they were significantly larger than effect sizes of biomarkers in 7 of the 9 comparisons. Conclusion: Baseline cognition and short-term practice effects appear to be sensitive markers in late life cognitive disorders, as they separated groups better than commonly-used biomarkers in AD. Further development of baseline cognition and short-term practice effects as tools for clinical diagnosis, prognostic indication, and enrichment of clinical trials seems warranted.