Meta-Analysis of Cognition in Parkinson's Disease Mild Cognitive Impairment and Dementia Progression.

Mild cognitive changes, including executive dysfunction, are seen in Parkinson's Disease (PD). Approximately 30% of individuals with PD develop Parkinson's disease dementia (PDD). Mild cognitive impairment (MCI) has been identified as a transitional state between normal cognition and dementia. Although PD-MCI and its cognitive correlates have been increasingly studied as a risk indicator for development of PDD, investigations into the PD-MCI construct have yielded heterogeneous findings. Thus, a typical PD-MCI cognitive profile remains undefined. The present meta-analysis examined published cross-sectional studies of PD-MCI and cognitively normal PD (PD-CN) groups to provide aggregated effect sizes of group test performance by cognitive domain. Subsequently, longitudinal studies examining PD-MCI to PDD progression were meta-analyzed. Ninety-two cross-sectional articles of PD-MCI vs. PD-CN were included; 5 longitudinal studies of PD-MCI conversion to PDD were included. Random effects meta-analytic models were constructed resulting in effect sizes (Hedges' g) for cognitive domains. Overall performance across all measures produced a large effect size (g = 0.83, 95% CI [0.79, 0.86], t2 = 0.18) in cross-sectional analyses, with cognitive screeners producing the largest effect (g = 1.09, 95% CI [1.00, 1.17], t2 = 0.19). Longitudinally, overall measures produced a moderate effect (g = 0.47, 95% CI [0.40, 0.53], t2 = 0.01), with measures of executive functioning exhibiting the largest effect (g = 0.70, 95% CI [0.51, 0.89], t2 = 0.01). Longitudinal effects were made more robust by low heterogeneity. This report provides the first comprehensive meta-analysis of PD-MCI cognitive outcomes and predictors in PD-MCI conversion to PDD. Limitations include heterogeneity of cross-sectional effect sizes and the potential impact of small-study effects. Areas for continued research include visuospatial skills and visual memory in PD-MCI and longitudinal examination of executive dysfunction in PD-MCI.

Primitive Reflexes and Dementia in Adults With Down Syndrome.

Background and Objectives: To determine whether primitive reflexes serve as an indicator of dementia in adults with Down syndrome (DS), we collected neurologic examination data, cognitive and behavioral assessments, and clinical consensus diagnoses of dementia from 92 adults with DS. Methods: In a cross-sectional, observational study of a regional cohort, χ2 and Fisher exact tests examined individual reflexes across the diagnostic group (no, possible, or probable dementia). In 64 participants with all 8 reflexes assessed, the number of primitive reflexes was assessed as a predictor of diagnosis using age-controlled multinomial logistic regression and of performance on clinical assessments (Brief Praxis Test [BPT], Severe Impairment Battery [SIB], and the Dementia Questionnaire for People with Learning Disabilities [DLD]) using age-adjusted linear regression. Results: Primitive palmomental, grasp, snout, and suck reflexes were more frequent in individuals with probable dementia, but all participants showed at least 1 primitive reflex. Multiple primitive reflexes in combination served as a better indicator of dementia, with each additional abnormal reflex tripling probability of the probable dementia group membership controlling for age. Abnormal reflex count was not associated with direct assessment of cognition and praxis (SIB and BPT) but associated with informant ratings of cognitive and behavioral functioning (DLD). Discussion: The presence of multiple reflexes serves as an indicator of dementia status in DS as a supplement to direct assessment of cognition and praxis. The reflex examination may serve as a tool in the multimethod evaluation for dementia in DS, as it appears unaffected by intellectual disability and language mastery.

Neurocognitive effects of Moyamoya disease and concomitant epilepsy.

Objective: Moyamoya disease (MMD) is a rare degenerative cerebrovascular disorder that leads to recurrent strokes and cerebral hypoperfusion. Seizures are not uncommon in MMD especially following surgical treatment for the disease. Cognitive changes that are largely executive in nature have been documented following MMD and surgical treatment, although research is limited in adults. Methods: The present case report details the comprehensive neurocognitive evaluation of a patient with MMD and concomitant epilepsy. Results: Neurocognitive findings revealed a prominent dysexecutive pattern and atypically poor performance in areas such as visual and verbal memory. The patient reported significant affective symptoms and functional decline. Conclusions: This case offers insight into unique neurocognitive results that may present in adult MMD cases and underscores the importance of interpreting results in the context of neurological comorbidities in this rare disease.

Cognitive and Behavioral Domains That Reliably Differentiate Normal Aging and Dementia in Down Syndrome.

Primary care integration of Down syndrome (DS)-specific dementia screening is strongly advised. The current study employed principal components analysis (PCA) and classification and regression tree (CART) analyses to identify an abbreviated battery for dementia classification. Scale- and subscale-level scores from 141 participants (no dementia n = 68; probable Alzheimer's disease n = 73), for the Severe Impairment Battery (SIB), Dementia Scale for People with Learning Disabilities (DLD), and Vineland Adaptive Behavior Scales-Second Edition (Vineland-II) were analyzed. Two principle components (PC1, PC2) were identified with the odds of a probable dementia diagnosis increasing 2.54 times per PC1 unit increase and by 3.73 times per PC2 unit increase. CART analysis identified that the DLD sum of cognitive scores (SCS < 35 raw) and Vineland-II community subdomain (<36 raw) scores best classified dementia. No significant difference in the PCA versus CART area under the curve (AUC) was noted (D(65.196) = -0.57683; p = 0.57; PCA AUC = 0.87; CART AUC = 0.91). The PCA sensitivity was 80% and specificity was 70%; CART was 100% and specificity was 81%. These results support an abbreviated dementia screening battery to identify at-risk individuals with DS in primary care settings to guide specialized diagnostic referral.

Diagnostic and prognostic performance and longitudinal changes in plasma neurofilament light chain concentrations in adults with Down syndrome: a cohort study.

BACKGROUND: Adults with Down syndrome are at an ultra-high risk of Alzheimer's disease, but diagnosis of Alzheimer's disease in this population is challenging. We aimed to validate the clinical utility of plasma neurofilament light chain (NfL) for the diagnosis of symptomatic Alzheimer's disease in Down syndrome, assess its prognostic value, and establish longitudinal changes in adults with Down syndrome. METHODS: We did a multicentre cohort study, including adults with Down syndrome (≥18 years), recruited from six hospitals and university medical centres in France, Germany, Spain, the UK, and the USA, who had been assessed, followed up, and provided at least two plasma samples. Participants were classified by local clinicians, who were masked to biomarker data, as asymptomatic (ie, no clinical suspicion of Alzheimer's disease), prodromal Alzheimer's disease, or Alzheimer's disease dementia. We classified individuals who progressed along the Alzheimer's disease continuum during follow-up as progressors. Plasma samples were analysed retrospectively; NfL concentrations were measured centrally using commercial kits for biomarker detection. We used ANOVA to evaluate differences in baseline NfL concentrations, Cox regression to study their prognostic value, and linear mixed models to estimate longitudinal changes. To account for potential confounders, we included age, sex, and intellectual disability as covariates in the analyses. FINDINGS: Between Aug 2, 2010, and July 16, 2019, we analysed 608 samples from 236 people with Down syndrome: 165 (70%) were asymptomatic, 32 (14%) had prodromal Alzheimer's disease, and 29 (12%) had Alzheimer's disease dementia; ten [4%] participants were excluded because their classification was uncertain. Mean follow-up was 3·6 years (SD 1·6, range 0·6-9·2). Baseline plasma NfL concentrations showed an area under the receiver operating characteristic curve of 0·83 (95% CI 0·76-0·91) in the prodromal group and 0·94 (0·90-0·97) in the dementia group for differentiating from participants who were asymptomatic. An increase of 1 pg/mL in baseline NfL concentrations was associated with a 1·04-fold risk of clinical progression (95% CI 1·01-1·07; p=0·0034). Plasma NfL concentrations showed an annual increase of 3·0% (95% CI 0·4-5·8) per year in the asymptomatic non-progressors group, 11·5% (4·9-18·5) per year in the asymptomatic progressors group, and 16·0% (8·4-24·0) per year in the prodromal Alzheimer's disease progressors group. In participants with Alzheimer's disease dementia, NfL concentrations increased by a mean of 24·3% (15·3-34·1). INTERPRETATION: Plasma NfL concentrations have excellent diagnostic and prognostic performance for symptomatic Alzheimer's disease in Down syndrome. The longitudinal trajectory of plasma NfL supports its use as a theragnostic marker in clinical trials. FUNDING: AC Immune, La Caixa Foundation, Instituto de Salud Carlos III, National Institute on Aging, Wellcome Trust, Jérôme Lejeune Foundation, Medical Research Council, National Institute for Health Research, EU Joint Programme-Neurodegenerative Disease Research, Alzheimer's society, Deutsche Forschungsgemeinschaft, Stiftung für die Erforschung von Verhaltens und Umwelteinflüssen auf die menschliche Gesundheit, and NHS National Institute of Health Research Applied Research Collaborations East of England, UK.

Longitudinal assessment of dementia measures in Down syndrome.

INTRODUCTION: Early detection of dementia symptoms is critical in Down syndrome (DS) but complicated by clinical assessment barriers. The current study aimed to characterize cognitive and behavioral impairment using longitudinal trajectories comparing several measures of cognitive and behavioral functioning. METHODS: Measures included global cognitive status (Severe Impairment Battery [SIB]), motor praxis (Brief Praxis Test [BPT]), and clinical dementia informant ratings (Dementia Questionnaire for People with Learning Disabilities [DLD]). One-year reliability was assessed using a two-way mixed effect, consistency, single measurement intraclass correlation among non-demented participants. Longitudinal assessment of SIB, BPT, and DLD was completed using linear mixed effect models. RESULTS: One-year reliability (n = 52; 21 male) was moderate for DLD (0.69 to 0.75) and good for SIB (0.87) and BPT (0.80). Longitudinal analysis (n = 72) revealed significant age by diagnosis interactions for SIB (F(2, 115.02) = 6.06, P = .003), BPT (F(2, 85.59) = 4.56, P = .013), and DLD (F(2, 103.56) = 4.48, P = .014). SIB progression (PR) had a faster decline in performance versus no-dementia (ND) (t(159) = -2.87; P = .013). Dementia had a faster decline in BPT performance versus ND (t(112) = -2.46; P = .041). PR showed quickly progressing scores compared to ND (t(128) = -2.86; P = .014). DISCUSSION: Current measures demonstrated moderate to good reliability. Longitudinal analysis revealed that SIB, BPT, and DLD changed with age depending on diagnostic progression; no change rates were dependent on baseline cognition, indicating usefulness across a variety of severity levels in DS.

Feasibility of dual-task gait to estimate Alzheimer's related cognitive decline in Down syndrome.

INTRODUCTION: The striatum and frontal lobes have been shown to have early Alzheimer's disease (AD) neuropathology and are critical for motor and cognitive function. We hypothesized gait would be associated with early-stage dementia in Down syndrome (DS), a cohort at risk for AD. METHODS: Twenty-eight participants with DS were enrolled in the study. Participants walked at their self-selected pace and while completing a dual task (counting, obstacle, or counting+obstacle). RESULTS: All participants were able to complete the self-paced condition and 78.57-96.42% completed the dual-task conditions. There was a trend for greater dual-task effects on gait velocity based on dementia diagnosis. Gait velocity had stronger associations with clinical dementia assessments than age or diagnosis. DISCUSSION: A dual-task gait paradigm is feasible to conduct with adults with DS and is associated with age and cognitive impairment. Dual-task gait may serve as an indicator of early stage dementia in DS.

Convergent and discriminant validity of the Immediate Postconcussion Assessment and Cognitive Testing Battery (ImPACT) in young athletes.

Sports concussions are recognized as significant injuries among young athletes. Research demonstrates that return-to-play prior to becoming asymptomatic has significant repercussions including sustained cognitive deficits. Many programs have begun to use computerized testing rather than traditional neuropsychological tests to (a) determine baseline performance, (b) track symptoms, and (c) measure symptoms following concussion. Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) is one such tool. The current study examined ImPACT's convergent and discriminant validity by comparing scores from sports-related concussion athletes (SRC) to those from nonconcussed controls (CTL). SRC included 29 athletes, ages 12-16, referred for neuropsychological assessment following sports-related concussions. CTL included 25 healthy athletes, ages 12-16, who were concussion-free in the past year. Overall, results showed general support for ImPACT, when used to screen cognition. In fact, all ImPACT domains successfully differentiated between SRC and CTL athletes. Evidence supporting appropriate convergent validity was best for the Visual Memory domain. Further, ImPACT domains demonstrated variable discriminant validity. Overall examination of validity demonstrated that ImPACT has some weaknesses but may have utility in detecting postconcussion cognitive impairment.

Chronic Neuropsychological Sequelae in a Patient with Nontumorous Anti-NMDA-Receptor Encephalitis.

Anti-N-methyl-D-aspartate receptor encephalitis is a neurological, autoimmune disorder tightly conceptualized only as recently as the mid-2000s. It presents itself in a combination of psychiatric, neurological, and autonomic features. We observe a unique case with probable earlier episode (prior to the mid-2000s conceptualization of the disease) and a later relapse, accompanying a comprehensive neuropsychological profile tracked after the relapse and subsequent improvement. Neurocognitive findings revealed residual frontal deficits with mood changes even in the state after plasmapheresis. This case is the first to describe posttreatment cognition in anti-NMDAR encephalitis after probable serial autoimmune episodes.