Cognitive and Clinical Characteristics of Patients With Limbic-Predominant Age-Related TDP-43 Encephalopathy.

BACKGROUND AND OBJECTIVES: Limbic-predominant age-related TDP-43 encephalopathy (LATE) affects similar neuroanatomical networks as Alzheimer disease (AD) and is often comorbid with AD, though frequently missed in clinical diagnosis. The primary aim of this study was to elucidate the clinical and cognitive differences at baseline between patients with autopsy-confirmed LATE and patients with AD and comorbid LATE + AD. METHODS: Clinical and neuropathologic datasets were requested from the National Alzheimer Coordination Center. Baseline data from individuals older than 75 years during death without neuropathologic indication of frontotemporal lobar degeneration were included in analyses. Pathologically defined groups reflecting LATE, AD, and comorbid LATE + AD were identified. Group differences in clinical characteristics and cognition were explored through analysis of variance and the χ2 using measures from the Uniform Data Set measures. RESULTS: Pathology groups included 31 individuals with LATE (mean age: 80.6 ± 5.4 years), 393 with AD (mean age: 77.8 ± 6.4 years), and 262 with LATE + AD (mean age: 77.8 ± 6.6 years) without significant differences in sex, education, or race. Compared with participants with AD and LATE + AD pathology, participants with LATE pathology lived significantly longer (mean visits: LATE = 7.3 ± 3.7; AD = 5.8 ± 3.0; and LATE + AD = 5.8 ± 3.0; F(2,683) = 3.7, p < 0.05), reported later onset of cognitive decline (mean onset: LATE = 78.8 ± 5.7; AD = 72.5 ± 7.0; and LATE + AD = 72.9 ± 7.0; F(2,516) = 6.2, p < 0.01), and were more likely to be diagnosed as cognitively normal at baseline (LATE = 41.9%; AD = 25.4%; and LATE + AD = 12%; χ2 = 38.7, p < 0.001). Individuals with LATE (45.2%) also reported fewer memory complaints than those with AD (74.4%) or LATE + AD (66.4%; χ2 = 13.3, p = 0.001) and were less likely to be classified as impaired on the Mini-Mental State Examination (LATE = 6.5%; AD = 24.2%; and LATE + AD = 40.1%; χ2 = 29.20, p < 0.001). Across all neuropsychological measures, participants with LATE + AD pathology performed significantly worse than the AD and LATE groups. DISCUSSION: Those with LATE pathology were older when cognitive symptoms began and lived longer than participants with AD or LATE + AD pathology. Participants with LATE pathology were also more likely to be classified as "cognitively normal" based on objective screening and self-report measures, and they had higher scores on neuropsychological testing. Consistent with prior literature, comorbid pathologies led to more significant cognitive and functional impairment. Early disease characteristics based on clinical presentation alone were insufficient for differentiating LATE from AD, reiterating the need for a validated biomarker.

Continuing education in diversity and multicultural factors: Current state psychology board requirements and a call to action.

Objective: A growing body of literature shows the unequivocal importance of incorporating diversity-related factors into the practice of clinical neuropsychology. Thus, it is imperative that we continue to seek and obtain updated training and knowledge on how culture and diversity intersect with our clinical roles throughout our careers, not merely to satisfy initial coursework requirements. Although most professional organizations pertaining to clinical psychology - and thereby neuropsychology - strongly encourage the pursuit of training in diversity-related factors, explicit requirements for such training across one's career are minimal. Method: The Asian Neuropsychological Association Advocacy Committee reviewed continuing education (CE) requirements for all US states. Results: We found that only 8 states mandated CE credits pertaining to diversity-related factors for the renewal of licensure. Discussion: Given how inseparable cultural competence is from any aspect of clinical work (and the harm that can be done if culture is not considered), it is essential that our field shift from aspirational guidance to firm requirements with regard to cultural competence and diversity-related training in psychology. Requiring CE units devoted to diversity-related factors represents one avenue to pursue this goal. This commentary outlines the current status of diversity-related CE for psychology licensure renewal and offers future directions for incorporating such training as a part of continuing professional development and education.

LGI1 antibody encephalitis: acute treatment comparisons and outcome.

OBJECTIVE: To compare acute treatment responses and long-term outcome in leucine-rich glioma-inactivated 1 (LGI1) antibody encephalitis. METHODS: Retrospective case series of 118 patients with LGI1 antibody encephalitis evaluated at Mayo Clinic across all US sites from 1 May 2008 to 31 March 2019. Patient clinical data were identified and analysed through the neuroimmunology laboratory and electronic medical record. LGI1 antibody detection was by cell-based indirect immunofluorescence assay of serum, cerebrospinal fluid or both. Clinical outcomes were faciobrachial dystonic seizure (FBDS) resolution, modified Rankin Scale (mRS) score, Kokmen Short Test of Mental Status (STMS) score (0-38 point scale) and neuropsychometric testing results. RESULTS: Compared with intravenous immunoglobulin (IVIg) (n=21), patients treated with single-agent acute corticosteroids (intravenous, oral or both) (n=49) were more likely to experience resolution of FBDS (61% vs 7%, p=0.002) and improvements in mRS score (ΔmRS score 2 vs 0, p=0.008) and median Kokmen STMS scores (ΔKokmen STMS score 5 points vs 0 points, p=0.01). In 54 patients with long-term follow-up (≥2 years), the median mRS score was 1 (range 0-6) and the median Kokmen STMS score was 36 (range 24-38) after all combinations of immunotherapy. Neuropsychometric testing in 32 patients with long-term follow-up (≥2 years) demonstrated short-term memory impairments in 37%. CONCLUSIONS: Corticosteroids appeared more effective acutely than IVIg in improving LGI1 antibody encephalitis in this retrospective comparison of immunotherapies. While improvement with immunotherapy is typical and long-term outcome is favourable, short-term memory deficits are noted in approximately a third of the patients.

A Comparison of Cross-Sectional and Longitudinal Methods of Defining Objective Subtle Cognitive Decline in Preclinical Alzheimer's Disease Based on Cogstate One Card Learning Accuracy Performance.

BACKGROUND: Longitudinal, but not cross-sectional, cognitive testing is one option proposed to define transitional cognitive decline for individuals on the Alzheimer's disease continuum. OBJECTIVE: Compare diagnostic accuracy of cross-sectional subtle objective cognitive impairment (sOBJ) and longitudinal objective decline (ΔOBJ) over 30 months for identifying 1) cognitively unimpaired participants with preclinical Alzheimer's disease defined by elevated brain amyloid and tau (A+T+) and 2) incident mild cognitive impairment (MCI) based on Cogstate One Card Learning (OCL) accuracy performance. METHODS: Mayo Clinic Study of Aging cognitively unimpaired participants aged 50 + with amyloid and tau PET scans (n = 311) comprised the biomarker-defined sample. A case-control sample of participants aged 65 + remaining cognitively unimpaired for at least 30 months included 64 who subsequently developed MCI (incident MCI cases) and 184 controls, risk-set matched by age, sex, education, and visit number. sOBJ was assessed by OCL z-scores. ΔOBJ was assessed using within subjects' standard deviation and annualized change from linear regression or linear mixed effects (LME) models. Concordance measures Area Under the ROC Curve (AUC) or C-statistic and odds ratios (OR) from conditional logistic regression models were derived. sOBJ and ΔOBJ were modeled jointly to compare methods. RESULTS: sOBJ and ΔOBJ-LME methods differentiated A+T+ from A-T- (AUC = 0.64, 0.69) and controls from incident MCI (C-statistic = 0.59, 0.69) better than chance; other ΔOBJ methods did not. ΔOBJ-LME improved prediction of future MCI over baseline sOBJ (p = 0.003) but not over 30-month sOBJ (p = 0.09). CONCLUSION: Longitudinal decline did not offer substantial benefit over cross-sectional assessment in detecting preclinical Alzheimer's disease or incident MCI.

Diagnostic accuracy of the Cogstate Brief Battery for prevalent MCI and prodromal AD (MCI A+ T+ ) in a population-based sample.

INTRODUCTION: This study evaluated the diagnostic accuracy of the Cogstate Brief Battery (CBB) for mild cognitive impairment (MCI) and prodromal Alzheimer's disease (AD) in a population-based sample. METHODS: Participants included adults ages 50+ classified as cognitively unimpaired (CU, n = 2866) or MCI (n = 226), and a subset with amyloid (A) and tau (T) positron emission tomography who were AD biomarker negative (A-T-) or had prodromal AD (A+T+). RESULTS: Diagnostic accuracy of the Learning/Working Memory Composite (Lrn/WM) for discriminating all CU and MCI was moderate (area under the curve [AUC] = 0.75), but improved when discriminating CU A-T- and MCI A+T+ (AUC = 0.93) and when differentiating MCI participants without AD biomarkers from those with prodromal AD (AUC = 0.86). Conventional cut-offs yielded lower than expected sensitivity for both MCI (38%) and prodromal AD (73%). DISCUSSION: Clinical utility of the CBB for detecting MCI in a population-based sample is lower than expected. Caution is needed when using currently available CBB normative data for clinical interpretation.

Diagnostic and Prognostic Accuracy of the Cogstate Brief Battery and Auditory Verbal Learning Test in Preclinical Alzheimer's Disease and Incident Mild Cognitive Impairment: Implications for Defining Subtle Objective Cognitive Impairment.

BACKGROUND: There are detectable cognitive differences in cognitively unimpaired (CU) individuals with preclinical Alzheimer's disease (AD). OBJECTIVE: To determine whether cross-sectional performance on the Cogstate Brief Battery (CBB) and Auditory Verbal Learning Test (AVLT) could identify 1) CU participants with preclinical AD defined by neuroimaging biomarkers of amyloid and tau, and 2) incident mild cognitive impairment (MCI)/dementia. METHOD: CU participants age 50+ were eligible if they had 1) amyloid (A) and tau (T) imaging within two years of their baseline CBB or 2) at least one follow-up visit. AUROC analyses assessed the ability of measures to differentiate groups. We explored the frequency of cross-sectional subtle objective cognitive impairment (sOBJ) defined as performance ≤-1 SD on CBB Learning/Working Memory Composite (Lrn/WM) or AVLT delayed recall using age-corrected normative data. RESULTS: A+T+ (n = 33, mean age 79.5) and A+T- (n = 61, mean age 77.8) participants were older than A-T- participants (n = 146, mean age 66.3), and comparable on sex and education. Lrn/WM did not differentiate A + T+or A+T- from A-T- participants. AVLT differentiated both A+T+ and A+T- from A-T- participants; 45% of A+T+ and 25% of A+T- participants met sOBJ criteria. The follow-up cohort included 150 CU individuals who converted to MCI/dementia and 450 age, sex, and education matched controls. Lrn/WM and AVLT differentiated between stable and converter CU participants. CONCLUSION: Among CU participants, AVLT helped differentiate A+T+ and A+T- from A-T- participants. The CBB did not differentiate biomarker subgroups, but showed potential for predicting incident MCI/dementia. Results inform future definitions of sOBJ.