Premorbid personality traits as predictors for incident predementia syndromes: a multistate model approach.

OBJECTIVE: Associations have been found between five-factor model (FFM) personality traits and risk of developing specific predementia syndromes such as subjective cognitive decline (SCD) and mild cognitive impairment (MCI). The aims of this study were to: 1) Compare baseline FFM traits between participants who transitioned from healthy cognition or SCD to amnestic MCI (aMCI) versus non-amnestic MCI (naMCI); and 2) Determine the relationship between FFM traits and risk of transition between predementia cognitive states. METHODS: Participants were 562 older adults from the Einstein Aging Study, 378 of which had at least one follow-up assessment. Baseline data collected included levels of FFM personality traits, anxiety and depressive symptoms, medical history, performance on a cognitive battery, and demographics. Follow-up cognitive diagnoses were also recorded. RESULTS: Mann-Whitney U tests revealed no differences in baseline levels of FFM personality traits between participants who developed aMCI compared to those who developed naMCI. A four-state multistate Markov model revealed that higher levels of conscientiousness were protective against developing SCD while higher levels of neuroticism resulted in an increased risk of developing SCD. Further, higher levels of extraversion were protective against developing naMCI. CONCLUSIONS: FFM personality traits may be useful in improving predictions of who is at greatest risk for developing specific predementia syndromes. Information on these personality traits could enrich clinical trials by permitting trials to target individuals who are at greatest risk for developing specific forms of cognitive impairment. These results should be replicated in future studies with larger sample sizes and younger participants.

The Effects of Cognitive Ability, Mental Health, and Self-Quarantining on Functional Ability of Older Adults During the COVID-19 Pandemic: Results From the Canadian Longitudinal Study on Aging.

OBJECTIVES: Determine whether levels of anxiety and depression, cognitive ability, and self-quarantining during and prior to the pandemic predict decreases in perceived functional ability. DESIGN AND SETTING: Longitudinal data collected from the Canadian Longitudinal Study on Aging (CLSA) COVID-19 Questionnaire Study (2020) and core CLSA study (Follow-Up 1; 2014-2018). PARTICIPANTS: 17 541 CLSA participants. MEASUREMENTS: Self-quarantining behaviours from questionnaires administered at Baseline (April 2020), Monthly, and Exit (December 2020) time points of the CLSA COVID-19 Questionnaire Study, levels of anxiety and depression at Baseline, perceived change in functional ability at Exit, and performance on neuropsychological tests (Rey Auditory Verbal Learning Task, Mental Alternation Task, Animal Fluency Test) and functional ability (Older Americans Resources and Services [OARS] Multidimensional Assessment Questionnaire) from the core CLSA study. RESULTS: Greater cognitive ability pre-pandemic (B = -.003, P < .01), higher levels of anxiety (B = -.024, P < .01) and depressive symptoms (B = -.110, P < .01) at Baseline, and higher frequency of engaging in self-quarantining throughout the COVID-19 survey period (B = -.098, P < .01) were associated with perceived loss in functional ability at Exit. Self-quarantining behaviour was associated with perceived loss in functional ability only at average and high levels of depressive symptoms (B = -.013, P < .01). CONCLUSIONS: Older adults with higher cognitive and lower functional ability prior to the pandemic were at greater risk of decreased perceived functional ability during the first year of the pandemic, as were those who experienced greater levels of anxiety and depressive symptoms during the pandemic. Strategies/interventions to preserve functional ability in older adults with cognitive independence prior to future pandemics are warranted.

A Systematic Review and Comparison of Neurocognitive Features of Late-Life Attention-Deficit/Hyperactivity Disorder and Dementia With Lewy Bodies.

OBJECTIVE: Attention-deficit/hyperactivity disorder (ADHD) in adulthood and dementia with Lewy bodies (DLB) share many cognitive and noncognitive similarities. The overlapping features between both disorders complicate differential diagnosis. The aim of the current systematic review was to compare patterns of neuropsychological profiles in older adults with ADHD and DLB. METHOD: Of the 1989 ADHD-related articles and 1332 DLB-related articles screened, 3 ADHD and 25 DLB articles were retained for qualitative synthesis and review. RESULTS: A synthesis of individual study findings revealed isolated working memory deficits for late-life ADHD, and performance deficits in areas of attention, memory, language, and visuoperceptual abilities for DLB. Results were limited by small samples and absence of data in some cognitive domains. CONCLUSION: These initial findings support potentially unique neurocognitive profiles for ADHD in later life and DLB that would enable practitioners to differentially diagnose and appropriately treat older adults presenting with these phenotypically similar disorders.

Combined Atlas and Convolutional Neural Network-Based Segmentation of the Hippocampus from MRI According to the ADNI Harmonized Protocol.

Hippocampus atrophy is an early structural feature that can be measured from magnetic resonance imaging (MRI) to improve the diagnosis of neurological diseases. An accurate and robust standardized hippocampus segmentation method is required for reliable atrophy assessment. The aim of this work was to develop and evaluate an automatic segmentation tool (DeepHarp) for hippocampus delineation according to the ADNI harmonized hippocampal protocol (HarP). DeepHarp utilizes a two-step process. First, the approximate location of the hippocampus is identified in T1-weighted MRI datasets using an atlas-based approach, which is used to crop the images to a region-of-interest (ROI) containing the hippocampus. In the second step, a convolutional neural network trained using datasets with corresponding manual hippocampus annotations is used to segment the hippocampus from the cropped ROI. The proposed method was developed and validated using 107 datasets with manually segmented hippocampi according to the ADNI-HarP standard as well as 114 multi-center datasets of patients with Alzheimer's disease, mild cognitive impairment, cerebrovascular disease, and healthy controls. Twenty-three independent datasets manually segmented according to the ADNI-HarP protocol were used for testing to assess the accuracy, while an independent test-retest dataset was used to assess precision. The proposed DeepHarp method achieved a mean Dice similarity score of 0.88, which was significantly better than four other established hippocampus segmentation methods used for comparison. At the same time, the proposed method also achieved a high test-retest precision (mean Dice score: 0.95). In conclusion, DeepHarp can automatically segment the hippocampus from T1-weighted MRI datasets according to the ADNI-HarP protocol with high accuracy and robustness, which can aid atrophy measurements in a variety of pathologies.

Visualization of atrophy of medial temporal lobes and the septal nuclei in patients with transient ischaemic attack and controls.

Introduction: Transient ischaemic attack (TIA) is associated with increased risk of cognitive decline and dementia as early as one-year post-event. Regional brain atrophy measurements may predict future cognitive decline. Aims: 1) To determine whether Medial Temporal Atrophy (MTA) scores and interseptal distance (ISD) measurements are greater in patients with TIA compared to controls; and 2) To determine whether MTA and ISD predicts cognitive change one year after TIA. Methods: Baseline demographic, vascular risk factors, structural imaging and cognitive tests scores were compared between 103 Patients with TIA and 103 age-and-sex-matched controls from the Predementia Neuroimaging of Transient Ischaemic Attack (PREVENT) Study. MTA was assessed using the Schelten's Scale, and ISD was calculated as the distance between the septal nucleus of each hemisphere. Multiple linear regression models were used to evaluate how MTA and ISD related to cognitive change after adjusting for covariates. Results: Patients with TIA had larger ISD measurements (1.4 mm [SD=1.2] vs. 0.9 mm [SD=1.0]); p < 0.001) and higher right/left MTA scores (both p < 0.05) compared to controls. At baseline, controls performed significantly better on the RAVLT (total recall), BVMT (total and delayed recall) and the Trail Making Task (A and B) compared to patients with TIA. However, at one-year follow-up there was no evidence of decline in the patients with TIA compared with controls. Higher MTA and ISD scores were not associated with cognitive decline. Conclusions: Patients with TIA had higher MTA scores and ISD measurements than controls, but neither were predictors of cognitive decline at one year. Future studies with longer follow-up periods will be required to determine whether higher MTA scores and ISD predict risk of cognitive decline in patients with TIA.

Capturing daily-life executive impairments in adults: Does the choice of neuropsychological tests matter?

OBJECTIVE: Standardized executive functioning (EF) measures do not reliably capture EF-related difficulties reported in daily life. We aim to determine if an ecologically relevant neuropsychological battery is more strongly associated with self-reported everyday EF impairments than classically used tests. METHOD: Fifty-nine adults aged 18-49 self-rated their EF abilities using the Barkley Deficits in EF Scale (BDEFS) and were randomly assigned to complete either a test battery composed of EF measures with hypothesized ecological relevance (Six Elements, Zoo Map, Hayling Sentence Completion, Iowa Gambling, and Auditory Startle Tasks) or one composed of traditional EF tasks (Card Sorting, Trail Making, Color-Word Interference, and Verbal Fluency). Associations were examined using linear regression. RESULTS: There were no strong associations between BDEFS subscales and performance on either test battery. Only the regression model predicting Emotional Regulation from ecological tasks was significant. Iowa Gambling Task performance and corrugator muscle contraction in the Auditory Startle Task individually contributed significantly to the model, with small and moderate effect sizes respectively. CONCLUSION: Results align with evidence that self-reported EF difficulties are not adequately captured by formal neuropsychological measures, even for performance-based measures which directly tap everyday constructs. Findings are interpreted cautiously in the context of a small, high-functioning sample.

The neuroimaging of neurodegenerative and vascular disease in the secondary prevention of cognitive decline.

Structural brain changes indicative of dementia occur up to 20 years before the onset of clinical symptoms. Efforts to modify the disease process after the onset of cognitive symptoms have been unsuccessful in recent years. Thus, future trials must begin during the preclinical phases of the disease before symptom onset. Age related cognitive decline is often the result of two coexisting brain pathologies: Alzheimer's disease (amyloid, tau, and neurodegeneration) and vascular disease. This review article highlights some of the common neuroimaging techniques used to visualize the accumulation of neurodegenerative and vascular pathologies during the preclinical stages of dementia such as structural magnetic resonance imaging, positron emission tomography, and white matter hyperintensities. We also describe some emerging neuroimaging techniques such as arterial spin labeling, diffusion tensor imaging, and quantitative susceptibility mapping. Recent literature suggests that structural imaging may be the most sensitive and cost-effective marker to detect cognitive decline, while molecular positron emission tomography is primarily useful for detecting disease specific pathology later in the disease process. Currently, the presence of vascular disease on magnetic resonance imaging provides a potential target for optimizing vascular risk reduction strategies, and the presence of vascular disease may be useful when combined with molecular and metabolic markers of neurodegeneration for identifying the risk of cognitive impairment.

Investigating the Association Between Verbal Forgetting and Pathological Markers of Alzheimer's and Lewy Body Diseases.

BACKGROUND: The percentage of verbal forgetting (VF%) measure of the Rey Auditory Verbal Learning Test (RAVLT) has been proposed to differentiate patients diagnosed clinically with Alzheimer's disease (AD) and dementia with Lewy bodies (DLB). OBJECTIVE: To determine if VF% aligns with gold-standard biomarker and autopsy evidence of AD and DLB neuropathology. METHODS: Clinical, cognitive, sociodemographic, and biomarker data were collected from 315 patients with baseline cognitive impairment and 485 normal controls from the Alzheimer's Disease Neuroimaging Initiative (ADNI). AD markers included reduced cerebrospinal fluid (CSF) amyloid-ß, elevated total-tau and phosphorylated-tau, hippocampal atrophy, and the presence of amyloid plaques and neurofibrillary tangles at autopsy. DLB markers included reduced CSF α-synuclein, preserved hippocampus, atrophied putamen, occipital glucose metabolism, and the presence of Lewy bodies at autopsy. Cognitively impaired participants were classified as ADVF% (n = 190) or DLBVF% (n = 125) based on their RAVLT VF% scores using a 75% cut-off (≥75%  = ADVF%, <75%  = DLBVF%). Postmortem data were available for 13 ADVF% participants, 13 DLBVF% patients, and six healthy controls. RESULTS: ADVF% and DLBVF% participants did not differ on CSF or neuroimaging biomarkers, with the exception of total tau levels which were higher in ADVF%. In the subset of participants with autopsy data, comorbid AD and DLB pathology was most frequent in ADVF% participants, and pure DLB pathology was most frequent in DLBVF% participants, however, these differences were not statistically significant. CONCLUSION: The RAVLT VF% measure does not reliably align with AD and DLB neuropathology in ADNI participants.