Cognitive domains affected post-COVID-19; a systematic review and meta-analysis.

BACKGROUND AND PURPOSE: This review aims to characterize the pattern of post-COVID-19 cognitive impairment, allowing better prediction of impact on daily function to inform clinical management and rehabilitation. METHODS: A systematic review and meta-analysis of neurocognitive sequelae following COVID-19 was conducted, following PRISMA-S guidelines. Studies were included if they reported domain-specific cognitive assessment in patients with COVID-19 at >4 weeks post-infection. Studies were deemed high-quality if they had >40 participants, utilized healthy controls, had low attrition rates and mitigated for confounders. RESULTS: Five of the seven primary Diagnostic and Statistical Manual of Mental Disorders (DSM-5) cognitive domains were assessed by enough high-quality studies to facilitate meta-analysis. Medium effect sizes indicating impairment in patients post-COVID-19 versus controls were seen across executive function (standardised mean difference (SMD) -0.45), learning and memory (SMD -0.55), complex attention (SMD -0.54) and language (SMD -0.54), with perceptual motor function appearing to be impacted to a greater degree (SMD -0.70). A narrative synthesis of the 56 low-quality studies also suggested no obvious pattern of impairment. CONCLUSIONS: This review found moderate impairments across multiple domains of cognition in patients post-COVID-19, with no specific pattern. The reported literature was significantly heterogeneous, with a wide variety of cognitive tasks, small sample sizes and disparate initial disease severities limiting interpretability. The finding of consistent impairment across a range of cognitive tasks suggests broad, as opposed to domain-specific, brain dysfunction. Future studies should utilize a harmonized test battery to facilitate inter-study comparisons, whilst also accounting for the interactions between COVID-19, neurological sequelae and mental health, the interplay between which might explain cognitive impairment.

Effect of Vagus Nerve Stimulation on Attention and Working Memory in Neuropsychiatric Disorders: A Systematic Review.

BACKGROUND: It has been suggested that vagus nerve stimulation (VNS) may enhance attention and working memory. The neuromodulator effects of VNS are thought to activate the release of neurotransmitters involving cognition and to promote neuronal plasticity. Therefore, VNS has been studied for its effects on attention and working memory impairment in neuropsychiatric disorders. OBJECTIVES: This study aimed to assess the effects of VNS on attention and working memory among patients with neuropsychiatric disorders, examine stimulation parameters, provide mechanistic hypotheses, and propose future studies using VNS. MATERIALS AND METHODS: We conducted a systematic review using electronic databases MEDLINE (Ovid), Embase (Ovid), Cochrane library, and PsycINFO (Ovid). Narrative analysis was used to describe the therapeutic effects of VNS on attention and working memory, describe stimulation parameters, and propose explanatory mechanisms. RESULTS: We identified 20 studies reporting VNS effects on attention and working memory in patients with epilepsy or mood disorders. For epilepsy, there was one randomized controlled trial from all 18 studies. It demonstrated no statistically significant differences in the cognitive tasks between active and control VNS. From a within-subject experimental design, significant improvement of working memory after VNS was demonstrated. One of three nonrandomized controlled trials found significantly improved attentional performance after VNS. The cohort studies compared VNS and surgery and found attentional improvement in both groups. Nine of 12 pretest-posttest studies showed improvement of attention or working memory after VNS. For mood disorders, although one study showed significant improvement of attention following VNS, the other did not. CONCLUSIONS: This review suggests that, although we identified some positive results from eligible studies, there is insufficient good-quality evidence to establish VNS as an effective intervention to enhance attention and working memory in persons with neuropsychiatric disorders. Further studies assessing the efficacy of such intervention are needed.

Neurology and neuropsychiatry of COVID-19: a systematic review and meta-analysis of the early literature reveals frequent CNS manifestations and key emerging narratives.

There is accumulating evidence of the neurological and neuropsychiatric features of infection with SARS-CoV-2. In this systematic review and meta-analysis, we aimed to describe the characteristics of the early literature and estimate point prevalences for neurological and neuropsychiatric manifestations.We searched MEDLINE, Embase, PsycINFO and CINAHL up to 18 July 2020 for randomised controlled trials, cohort studies, case-control studies, cross-sectional studies and case series. Studies reporting prevalences of neurological or neuropsychiatric symptoms were synthesised into meta-analyses to estimate pooled prevalence.13 292 records were screened by at least two authors to identify 215 included studies, of which there were 37 cohort studies, 15 case-control studies, 80 cross-sectional studies and 83 case series from 30 countries. 147 studies were included in the meta-analysis. The symptoms with the highest prevalence were anosmia (43.1% (95% CI 35.2% to 51.3%), n=15 975, 63 studies), weakness (40.0% (95% CI 27.9% to 53.5%), n=221, 3 studies), fatigue (37.8% (95% CI 31.6% to 44.4%), n=21 101, 67 studies), dysgeusia (37.2% (95% CI 29.8% to 45.3%), n=13 686, 52 studies), myalgia (25.1% (95% CI 19.8% to 31.3%), n=66 268, 76 studies), depression (23.0% (95% CI 11.8% to 40.2%), n=43 128, 10 studies), headache (20.7% (95% CI 16.1% to 26.1%), n=64 613, 84 studies), anxiety (15.9% (5.6% to 37.7%), n=42 566, 9 studies) and altered mental status (8.2% (95% CI 4.4% to 14.8%), n=49 326, 19 studies). Heterogeneity for most clinical manifestations was high.Neurological and neuropsychiatric symptoms of COVID-19 in the pandemic's early phase are varied and common. The neurological and psychiatric academic communities should develop systems to facilitate high-quality methodologies, including more rapid examination of the longitudinal course of neuropsychiatric complications of newly emerging diseases and their relationship to neuroimaging and inflammatory biomarkers.

Validation of the Thai version of the short Boston Naming Test (T-BNT) in patients with Alzheimer's dementia and mild cognitive impairment: clinical and biomarker correlates.

OBJECTIVES: Impairments in the Boston Naming Test (BNT), which measures confrontational word retrieval, frequently accompanies Alzheimer's dementia (AD) and may predict a more rapid progression of illness. This study aims to validate the Thai version of the 15-item BNT (T-BNT) in participants with AD and amnestic mild cognitive impairment (aMCI) and to externally validate the T-BNT using clinical and biomarker measurements. METHODS: This cross-sectional study recruited patients with AD, diagnosed according to NINCDS-ADRDA criteria (n = 60), aMCI, diagnosed using the Petersen criteria (n = 60), and healthy controls (n = 62). We examined the internal consistency, concurrent and discriminant reliability of the T-BNT. We also assessed the Mini Mental State Examination (MMSE), the Verbal Fluency Test (VFT) and the Word List Memory (WLM) tests and measured apolipoprotein E polymorphism and serum levels of folic acid, high-density lipoprotein cholesterol (HDL) and triglycerides. RESULTS: This study validated a 10-item T-BNT (10T-BNT), which yielded good internal consistency (0.92), a one-factor unidimensional structure, and adequate concurrent and discriminant validity. Lower scores on the 10T-BNT highly significantly predict AD, but not aMCI, and are positively associated with VFT and WLM test scores. Furthermore, lowered 10T-BNT scores are significantly associated with the ApoE4 allele, lower folate levels and an increased triglyceride/HDL-cholesterol ratio. CONCLUSIONS: This study validated the 10T-BNT and the total score on this scale is strongly associated with AD, impairments in semantic and episodic memory and biomarkers, which are known to modify memory via different mechanisms.

Reliability and minimal detectable change of nonlinear analysis measure of postural control in older adults with mild cognitive impairment.

BACKGROUND: Evaluating quiet stance under various conditions using nonlinear analysis may be an effective method of measuring postural control in older adults with mild cognitive impairment (MCI). However, no studies have examined the reliability of using sample entropy (SampEn) in older adults with MCI. RESEARCH QUESTION: What are the within- and between-session reliability and minimal detectable change (MDC) of a nonlinear analysis measure of postural control during quiet stance in older adults with MCI? METHODS: Fourteen older adults with MCI performed static standing under four conditions, and the center of pressure signal was calculated and applied to SampEn nonlinear analysis. The within- and between-session reliability and MDC were explored. RESULTS: Within-session reliability was found to be fair to good and excellent (ICC = 0.527-0.960), and between-session reliability was excellent (ICC = 0.795-0.979). MDC values were less than 0.15. SIGNIFICANCE: The between-session reliability of SampEn in all conditions demonstrates SampEn's stable performance. This method may be useful in assessing postural control in older adults with MCI, and MDC values may be helpful in detecting subtle changes in patient performance.

Biomechanics of sit-to-stand with dual tasks in older adults with and without mild cognitive impairment.

BACKGROUND: The decline in cognitive function in older adults with mild cognitive impairment (MCI) may contribute to a change in movement pattern during sit-to-stand transitions (STS). However, when comparing older adults with MCI to older adults without MCI, there is a lack of evidence of kinematic and kinetic data during STS. Furthermore, while significant cognitive dual-task interference has been demonstrated in older adults with MCI, studies on the effects of dual motor tasks in MCI, particularly during STS, have not been reported. RESEARCH QUESTION: Are there any differences in the movement time, joint angles, and maximum joint moments while performing STS under single- and dual-task conditions in older adults with and without MCI? METHODS: In a cross-sectional study, 70 participants were divided into two groups: older adults with MCI and without MCI. Motion analysis and a force plate system were used to collect and analyze the STS movement. All participants were asked to do the STS movement alone and the STS with a dual motor task with the self-selected pattern on an adjustable bench. RESULTS: Older adults with MCI had greater maximum trunk flexion during STS with a dual task than older adults without MCI and greater than STS alone. Furthermore, older adults with MCI had a greater ankle plantar flexion moment during STS with a dual task than during STS alone. SIGNIFICANCE: Even though the STS task is one of the simplest functional activities, different strategies to achieve the STS action with dual tasks were found among older adults with and without MCI in terms of joint angle and joint moments.

CYP2D6 Predicts Plasma Donepezil Concentrations in a Cohort of Thai Patients with Mild to Moderate Dementia.

PURPOSE: Donepezil, a drug frequently used to treat dementia, is mainly metabolized by cytochrome P450 2D6 (CYP2D6). This study investigated the relationships between CYP2D6 genotype and activity scores as well as predicted phenotype of plasma donepezil concentrations in 86 Thai dementia participants. MATERIALS AND METHODS: CYP2D6 was genotyped using bead-chip technology (Luminex xTAG® v.3). Steady-state trough plasma donepezil concentrations were measured using high-performance liquid chromatography. RESULTS: Sixteen genotypes were found but the most frequent genotypes detected among our participants were CYP2D6*10/*10 (27.9%) and *1/*10 (26.7%). One-third of the participants had an activity score of 1.25 which predicted that they were normal metabolizers. The overall median (interquartile range) of plasma donepezil concentration was 51.20 (32.59-87.24) ng/mL. Normal metabolizers (NMs) had lower plasma donepezil concentrations compared to intermediate metabolizers (IMs) (41.15 (28.44-67.65) ng/mL vs 61.95 (35.25-97.00) ng/mL). Multivariate analysis showed that CYP2D6 activity score (r2 = 0.50) and the predicted phenotype (independent of dose) could predict the plasma donepezil concentration (r2 = 0.49). CONCLUSION: Plasma donepezil concentration in NMs was lower compared to IMs. Additional studies with larger sample size and use of next-generation sequencing as well as its outcomes are warranted to confirm the benefit of using pharmacogenetic-guided treatment for donepezil.

Early prediction of donepezil cognitive response in Alzheimer's disease by brain perfusion single photon emission tomography.

Currently, there is no effective means to evaluate donepezil response. We evaluated brain perfusion change at 4 h after donepezil administration (4 h DNPZ) to predict cognitive responses after 6 months of medication. CERAD neuropsychological assessment battery was used to define cognitive response at 6 months. We compared 4 h DNPZ to baseline single photon emission tomography (SPECT) by statistical parametric mapping to identify perfusion changes in responders (N = 16) and non-responders (N = 7). In responders, there were significant relatively increase in perfusion in left parietal lobe (BA39, 7, 1), right superior frontal gyrus (BA6) and right middle occipital gyrus (BA39). In the non-responders, perfusion was relatively increase in the left parietal lobe (BA39) only. In an explorative analysis, we found a significant correlation between perfusion changes in right BA6 and CERAD score changes at 6 months. Different SPECT perfusion changes at 4 h after donepezil administration were demonstrated in the group of responders and non-responders with potential correlation with CERAD score change. Thus, 4 h DNPZ brain perfusion SPECT can be used to predict donepezil response at 6 months.

Peripheral Blood Biomarkers Coupled with the Apolipoprotein E4 Genotype Are Strongly Associated with Semantic and Episodic Memory Impairments in Elderly Subjects with Amnestic Mild Cognitive Impairment and Alzheimer's Disease.

BACKGROUND: The Apolipoprotein E4 (ApoE4) genotype is strongly associated with Alzheimer's disease (AD), although the presence of the ApoE4 allele alone is not sufficient to explain AD. The pathophysiology of amnestic mild cognitive impairment (aMCI) remains unclear. OBJECTIVE: This study aims to examine associations between peripheral blood biomarkers coupled with ApoE4 and episodic and semantic memory. METHODS: The CERAD battery was completed and various biomarkers were assayed in 60 subjects with aMCI, 60 with AD, and 62 healthy controls. RESULTS: Deficits in semantic and episodic memory were significantly predicted by anion gap and bicarbonate, albumin, and glucose coupled with ApoE4. Furthermore, these peripheral biomarkers interacted with ApoE to predict greater memory impairments. CONCLUSIONS: Peripheral blood biomarkers may interact with pathways related to ApoE4 to predict greater semantic and episodic memory impairments, thus contributing to the pathophysiology of aMCI and AD. Our data suggest that the transition from aMCI to AD could at least in some cases be associated with significant interactions between ApoE4 and those peripheral blood biomarkers.