A Cluster Analysis of Neuropsychological Impairment in Borderline Personality Disorder: Identifying a Neurocognitive Subtype Linked to Attention Deficit Hyperactivity Disorder.

INTRODUCTION: Cognitive impairment associated with borderline personality disorder (BPD) has been consistently demonstrated. However, a specific neuropsychological profile has not yet been established for this disorder, maybe due to the heterogeneity of BPD. The aim of this work is the search for distinct neuropsychological subtypes among patients with BPD and for the association of neuropsychological subgroups with specific clinical characteristics. METHODOLOGY: One hundred fifteen patients with BPD diagnosis received an extensive neuropsychological evaluation assessing attentional, memory and executive functions indexes. For subtyping strategies, a cluster analysis of neuropsychological BPD distribution was performed. Central clinical dimensions of BPD were measured and analysed in relation with the obtained neuropsychological clusters. RESULTS: Two clusters were found: Cluster 1 showed a significantly lower score on the working memory index, and Cluster 2 had significantly worse overall executive performance, response inhibition and planning abilities. Patients in the neurocognitive Cluster 2 showed significantly higher clinical deficits of attention as measured with subscales of the CAARS attention deficit hyperactivity disorder (ADHD) index (F = 2.549, p < 0.005, d = 11.49). CONCLUSIONS: Two neuropsychological clusters of patients were found in the BPD sample: Cluster 1 patients showed greater impairment in working memory, while Cluster 2 patients had greater deficits of executive functioning, particularly for response inhibition and planning. In addition, BPD patients with greater executive deficits presented greater levels of ADHD clinical features. These findings might also facilitate earlier diagnosis of severe BPD patient profiles and to establish more personalized treatment based on neurocognitive stimulation.

Minimal clinically important difference in Alzheimer's disease: Rapid review.

INTRODUCTION: We conducted a rapid systematic review of minimal clinically important differences (MCIDs) for Alzheimer's disease (AD) trial endpoints. METHODS: Two reviewers searched EMBASE, MEDLINE, and PubMed from inception to June 4, 2023. RESULTS: Ten articles were retrieved. For mild cognitive impairment (MCI), a change of +2 to +3 points on the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), +1 points on the Clinical Dementia Rating scale sum of boxes (CDR-SB), -5 points on the integrated Alzheimer's Disease Rating Scale (iADRS), or -1 to -2 points on the Mini-Mental State Examination (MMSE) was considered meaningful. For patients with mild AD, a change of +3 on the ADAS-Cog, +2 points on CDR-SB, -9 points on the iADRS, or -2 points on the MMSE was considered meaningful. For patients with moderate to severe AD, a change of +2 points on the CDR-SB or a change of -1.4 to -3 points on the MMSE was considered meaningful. CONCLUSION: This review identified previously published MCIDs for AD trial endpoints. Input from patients and caregivers will be needed to derive more meaningful endpoints and thresholds. HIGHLIGHTS: This systematic rapid review identified thresholds for minimal clinically important differences (MCIDs) for recently used Alzheimer's disease (AD) trial endpoints: Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), Clinical Dementia Rating scale sum of boxes (CDR-SB), integrated Alzheimer's Disease Rating Scale (iADRS), Mini-Mental State Examination (MMSE). MCIDs were higher for more severe stages of AD. Average treatment effects in recent trials of anti-amyloid disease modifying monoclonal antibodies are lower than previously published MCIDs. In future trials of disease modifying treatments for AD, the proportion of participants in each treatment group that experienced a clinically meaningful decline could be reported. More work is needed to incorporate the values and preferences of patients and care partners in deriving MCIDs.

Psychiatric symptoms, associated pharmacological treatments and cognitive function: A population-based study of men.

BACKGROUND: Psychiatric symptomatology and medications used in their treatment may be modifiable risk factors associated with cognitive function, although findings from population-based studies spanning the full adult age range are lacking. This study aimed to investigate associations between psychiatric symptomatology, psychotropic medication use and cognitive function in a population-based sample of men. METHODS: Data for 537 men were drawn from the Geelong Osteoporosis Study. Cognitive function (psychomotor function, attention, working memory and visual learning) was determined using the Cog-State Brief Battery. Current depressive and anxiety symptomatology was determined using the Hospital Anxiety and Depression Scale, and psychotropic medication use was self-reported. Linear regression models were developed to determine associations between psychiatric symptomatology and psychotropic medication use with each cognitive measure. RESULTS: Depressive symptomatology was associated with lower overall cognitive function (b-0.037 ± 0.010, η2 = 0.025, p < 0.001), psychomotor function (b 0.006 ± 0.002, η2 = 0.028 p < 0.001) and attention (b 0.004 ± 0.001, η2 = 0.021, p < 0.001), whereas psychotropic use was associated with lower overall cognitive function (b - 0.174 ± 0.075, η2 = 0.010, p = 0.021), attention (b 0.017 ± 0.008, η2 = 0.008, p = 0.038 and working memory (b 0.031 ± 0.012, η2 = 0.010, p = 0.010). Anticonvulsant use was associated with lower overall cognitive function (b - 0.723 ± 0.172, η2 = 0.032, p < 0.001), attention (b 0.065 ± 0.018, η2 = 0.029, p < 0.001) and working memory (b 0.088 ± 0.026, η2 = 0.022, p < 0.001). All relationships were found to have a small effect. There were no significant associations between anxiety symptomatology and antidepressant and anxiolytic use with any of the cognitive domains. CONCLUSION: Depressive symptomatology and anticonvulsant use were associated with lower cognitive function. Understanding the underlying mechanisms involved in these relationships can advance knowledge on the heterogeneity in cognitive ageing and aid in prevention initiatives.

Data-driven classification of cognitively normal and mild cognitive impairment subtypes predicts progression in the NACC dataset.

INTRODUCTION: Data-driven neuropsychological methods can identify mild cognitive impairment (MCI) subtypes with stronger associations to dementia risk factors than conventional diagnostic methods. METHODS: Cluster analysis used neuropsychological data from participants without dementia (mean age = 71.6 years) in the National Alzheimer's Coordinating Center (NACC) Uniform Data Set (n = 26,255) and the "normal cognition" subsample (n = 16,005). Survival analyses examined MCI or dementia progression. RESULTS: Five clusters were identified: "Optimal" cognitively normal (oCN; 13.2%), "Typical" CN (tCN; 28.0%), Amnestic MCI (aMCI; 25.3%), Mixed MCI-Mild (mMCI-Mild; 20.4%), and Mixed MCI-Severe (mMCI-Severe; 13.0%). Progression to dementia differed across clusters (oCN < tCN < aMCI < mMCI-Mild < mMCI-Severe). Cluster analysis identified more MCI cases than consensus diagnosis. In the "normal cognition" subsample, five clusters emerged: High-All Domains (High-All; 16.7%), Low-Attention/Working Memory (Low-WM; 22.1%), Low-Memory (36.3%), Amnestic MCI (16.7%), and Non-amnestic MCI (naMCI; 8.3%), with differing progression rates (High-All < Low-WM = Low-Memory < aMCI < naMCI). DISCUSSION: Our data-driven methods outperformed consensus diagnosis by providing more precise information about progression risk and revealing heterogeneity in cognition and progression risk within the NACC "normal cognition" group.

Differences in fractional amplitude of low-frequency fluctuations (fALFF) and cognitive function between untreated major depressive disorder and schizophrenia with depressive mood patients.

BACKGROUND: Distinguishing untreated major depressive disorder without medication (MDD) from schizophrenia with depressed mood (SZDM) poses a clinical challenge. This study aims to investigate differences in fractional amplitude of low-frequency fluctuations (fALFF) and cognition in untreated MDD and SZDM patients. METHODS: The study included 42 untreated MDD cases, 30 SZDM patients, and 46 healthy controls (HC). Cognitive assessment utilized the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Resting-state functional magnetic resonance imaging (rs-fMRI) scans were conducted, and data were processed using fALFF in slow-4 and slow-5 bands. RESULTS: Significant fALFF changes were observed in four brain regions across MDD, SZDM, and HC groups for both slow-4 and slow-5 fALFF. Compared to SZDM, the MDD group showed increased slow-5 fALFF in the right gyrus rectus (RGR). Relative to HC, SZDM exhibited decreased slow-5 fALFF in the left gyrus rectus (LGR) and increased slow-5 fALFF in the right putamen. Changes in slow-5 fALFF in both RGR and LGR were negatively correlated with RBANS scores. No significant correlations were found between remaining fALFF (slow-4 and slow-5 bands) and RBANS scores in MDD or SZDM groups. CONCLUSIONS: Alterations in slow-5 fALFF in RGR may serve as potential biomarkers for distinguishing MDD from SZDM, providing preliminary insights into the neural mechanisms of cognitive function in schizophrenia.

Eye Tracking During Visual Paired-Comparison Tasks: A Systematic Review and Meta-Analysis of the Diagnostic Test Accuracy for Detecting Cognitive Decline.

Background: Alzheimer's disease and mild cognitive impairment (MCI) progress silently, making early diagnosis challenging, especially in less educated populations. The visual paired comparison (VPC) task, utilizing eye-tracking movement (ETM) technology, offers a promising alternative for early detection of memory decline. Objective: This systematic review and meta-analysis evaluated the efficacy of the VPC task, utilizing ETM as a tool for assessing age-related cognitive changes. Methods: A comprehensive search across five databases and grey literature focused on healthy and impaired memory participants assessed through the ETM-based VPC task. The primary outcomes were novelty preference scores and eye movement metrics. The risk of bias of the included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2). Random-effects meta-analyses calculated Hedges' g effect size. Sensitivity and specificity of the VPC were meta-analytically pooled. Results: The systematic review included 12 articles, involving 1,022 participants (aged 18 to 90 years, with education ranging from 6.5 to 20.0 years), with a low risk of bias and minimal applicability concerns across all items. Five studies contributed to the meta-analysis, revealing a significant effect favoring the VPC task for recognition memory detection (k = 9, g = -1.03). Pooled sensitivity and specificity analyses demonstrated VPC effectiveness as a recognition memory assessment tool (0.84 and 0.75, respectively). Conclusions: The VPC task, utilizing ETM, may serve as a biomarker for early memory decline detection. Its use as a digital eye-tracking tool presents a possible alternative to traditional tests, warranting further research for application in neurodegenerative disease diagnosis.

The time course of motor and cognitive decline in older adults and their associations with brain pathologies: a multicohort study.

BACKGROUND: Many studies have reported that impaired gait precedes cognitive impairment in older people. We aimed to characterise the time course of cognitive and motor decline in older individuals and the association of these declines with the pathologies of Alzheimer's disease and related dementias. METHODS: This multicohort study used data from three community-based cohort studies (Religious Orders Study, Rush Memory and Aging Project, and Minority Aging Research Study, all in the USA). The inclusion criteria for all three cohorts were no clinical dementia at the time of enrolment and consent to annual clinical assessments. Eligible participants consented to post-mortem brain donation and had post-mortem pathological assessments and three or more repeated annual measures of cognition and motor functions. Clinical and post-mortem data were analysed using functional mixed-effects models. Global cognition was based on 19 neuropsychological tests, a hand strength score was based on grip and pinch strength, and a gait score was based on the number of steps and time to walk 8 feet and turn 360°. Brain pathologies of Alzheimer's disease and related dementias were assessed at autopsy. FINDINGS: From 1994 to 2022, there were 1570 eligible cohort participants aged 65 years or older, 1303 of whom had cognitive and motor measurements and were included in the analysis. Mean age at death was 90·3 years (SD 6·3), 905 (69%) participants were female, and 398 (31%) were male. Median follow-up time was 9 years (IQR 5-11). On average, cognition was stable from 25 to 15 years before death, when cognition began to decline. By contrast, gait function and hand strength declined during the entire study. The combinations of pathologies of Alzheimer's disease and related dementias associated with cognitive and motor decline and their onsets of associations varied; only tau tangles, Parkinson's disease pathology, and macroinfarcts were associated with decline of all three phenotypes. Tau tangles were significantly associated with cognitive decline, gait function decline, and hand function decline (p<0·0001 for each); however, the association with cognitive decline persisted for more than 11 years before death, but the association with hand strength only began 3·57 years before death and the association with gait began 3·49 years before death. By contrast, the association of macroinfarcts with declining gait function began 9·25 years before death (p<0·0001) compared with 6·65 years before death (p=0·0005) for cognitive decline and 2·66 years before death (p=0·024) for decline in hand strength. INTERPRETATION: Our findings suggest that average motor decline in older adults precedes cognitive decline. Macroinfarcts but not tau tangles are associated with declining gait function that precedes cognitive decline. This suggests the need for further studies to test if gait impairment is a clinical proxy for preclinical vascular cognitive impairment. FUNDING: National Institutes of Health.

Altered cerebral white matter network topology and cognition in children with obstructive sleep apnea.

OBJECTIVES: The study aimed to explore the underlying mechanisms of OSA-related cognitive impairment by investigating the altered topology of brain white matter networks in children with OSA. METHODS: Graph theory was used to examine white matter networks' network topological properties in 46 OSA and 31 non-OSA children. All participants underwent MRI, polysomnography, and cognitive testing. The effects of the obstructive apnea-hypopnea index (OAHI) on topological properties of white matter networks and network properties on cognition were studied using hierarchical linear regression. Mediation analyses were used to explore whether white matter network properties mediated the effects of OAHI on cognition. RESULTS: Children with OSA had significantly higher assortativity than non-OSA children. Furthermore, OAHI was associated with the nodal properties of several brain regions, primarily in the frontal and temporal lobes. The relationship between OAHI and verbal comprehension index was mediated through clustering coefficients in the right temporal pole of the superior temporal gyrus. CONCLUSIONS: OSA affects the development of white matter networks in children's brains. Besides, the mediating role of white matter network properties between the OAHI and the verbal comprehension index provided neuroimaging evidence of impaired cognitive function in children with OSA.

Subjective and objective assessments of executive functions are independently predictive of aggressive tendencies in patients with substance use disorder.

BACKGROUND AND AIMS: Impairments in executive functions have been found to influence violent behavior. Executive functions are crucial in the treatment of patients with substance use disorders because substance use generally impairs cognitive processes and is therefore detrimental for executive functions thereby reducing control of behavior and thus of consumption impulses. We studied correlations between subjective, i.e. self-report, and objective, i.e. behavior-based, assessment of executive functions and the predictive validity of these measures for aggression in patients with substance use disorder. METHODS: The study included 64 patients with a diagnosed substance use disorder who were convicted according to the German Criminal Code for crimes they committed in the context of their disorder and were therefore in treatment in forensic psychiatric departments in Germany. Multiple self-report and behavior-based instruments were used to assess executive functions, appetitive and facilitative aggression as well as clinical and sociodemographic variables. RESULTS: Participants showed impaired executive functions, and measures of executive functions predicted aggressive tendencies and violent offenses. Despite ecological validity of the findings, the subjective and objective assessments of executive functions did not correlate with each other, which corroborates studies in other clinical settings. CONCLUSIONS: We discuss that this finding may be due to the conceptual differences between subjective and objective measures. Therefore, self-report and behavior-based measures should not be used as proxies of each other but as complementary measures that are useful for comprehensive diagnostics of cognitive impairments and assessment of risks for violent behavior.

Racial and ethnic differences in the association between depressive symptoms and cognitive outcomes in older adults: Findings from KHANDLE and STAR.

INTRODUCTION: Depressive symptoms are associated with higher risk of dementia, but how they impact cognition in diverse populations is unclear. METHODS: Asian, Black, Latino, or White participants (n = 2227) in the Kaiser Healthy Aging and Diverse Life Experiences (age 65+) and the Study of Healthy Aging in African Americans (age 50+) underwent up to three waves of cognitive assessments over 4 years. Multilevel models stratified by race/ethnicity were used to examine whether depressive symptoms were associated with cognition or cognitive decline and whether associations differed by race/ethnicity. RESULTS: Higher depressive symptoms were associated with lower baseline verbal episodic memory scores (-0.06, 95% CI: -0.12, -0.01; -0.15, 95% CI: -0.25, -0.04), and faster decline annually in semantic memory (-0.04, 95% CI: -0.07, -0.01; -0.10, 95% CI: -0.15, -0.05) for Black and Latino participants. Depressive symptoms were associated with lower baseline but not decline in executive function. DISCUSSION: Depressive symptoms were associated with worse cognitive outcomes, with some evidence of heterogeneity across racial/ethnic groups. HIGHLIGHTS: We examined whether baseline depressive symptoms were differentially associated with domain-specific cognition or cognitive decline by race/ethnicity. Depressive symptoms were associated with worse cognitive scores for all racial/ethnic groups across different domains examined. Higher depressive symptoms were associated with faster cognitive decline for semantic memory for Black and Latino participants. The results suggest a particularly harmful association between depressive symptoms and cognition in certain racial/ethnic groups.

Association between hippocampal microglia, AD and LATE-NC, and cognitive decline in older adults.

INTRODUCTION: This study investigates the relationship between microglia inflammation in the hippocampus, brain pathologies, and cognitive decline. METHODS: Participants underwent annual clinical evaluations and agreed to brain donation. Neuropathologic evaluations quantified microglial burden in the hippocampus, amyloid beta (Aß), tau tangles, and limbic age-related transactive response DNA-binding protein 43 (TDP-43) encephalopathy neuropathologic changes (LATE-NC), and other common brain pathologies. Mixed-effect and linear regression models examined the association of microglia with a decline in global and domain-specific cognitive measures, and separately with brain pathologies. Path analyses estimated direct and indirect effects of microglia on global cognition. RESULT: Hippocampal microglia were associated with a faster decline in global cognition, specifically in episodic memory, semantic memory, and perceptual speed. Tau tangles and LATE-NC were independently associated with microglia. Other pathologies, including Aß, were not related. Regional hippocampal burden of tau tangles and TDP-43 accounted for half of the association of microglia with cognitive decline. DISCUSSION: Microglia inflammation in the hippocampus contributes to cognitive decline. Tau tangles and LATE-NC partially mediate this association.

Dementia and mild cognitive impairment screening in an emergency homeless shelter.

INTRODUCTION: Older adults represent the fastest growing segment of the homeless community. Little is known about the prevalence of dementia and mild cognitive impairment (MCI) in this population. METHODS: Dementia and MCI screening using the Montreal Cognitive Assessment (MoCA) was incorporated into the standard senior evaluation for adult clients aged ≥ 55 in a large emergency homeless shelter. RESULTS: In a 6-week period, 104 of 112 (92.9%) assessments were positive for dementia or MCI using a standard cutoff of 26, and 81 (72.3%) were positive using a conservative cutoff of 23. There was no significant difference in MoCA scores based on sex or education level, and no significant correlation between age and MoCA score. DISCUSSION: Older adults experiencing homelessness may have a high likelihood of dementia or MCI. Routine MoCA screening in older adults experiencing homelessness is feasible and can help to identify services needed to successfully exit homelessness.

Delineating cognitive resilience using fractal regulation: Cross-sectional and longitudinal evidence from the Rush Memory and Aging Project.

INTRODUCTION: Degradation of fractal patterns in actigraphy independently predicts dementia risk. Such observations motivated the study to understand the role of fractal regulation in the context of neuropathologies. METHODS: We examined associations of fractal regulation with neuropathologies and longitudinal cognitive changes in 533 older participants who were followed annually with actigraphy and cognitive assessments until death with brain autopsy performed. Two measures for fractal patterns were extracted from actigraphy, namely, α1 (representing the fractal regulation at time scales of <90 min) and α2 (for time scales 2 to 10 h). RESULTS: We found that larger α1 was associated with lower burdens of Lewy body disease or cerebrovascular disease pathologies; both α1 and α2 were associated with cognitive decline. They explained an additional significant portion of the variance in the rate of cognitive decline above and beyond neuropathologies. DISCUSSION: Fractal patterns may be used as a biomarker for cognitive resilience against dementia-related neuropathologies.

Longitudinal normative standards for cognitive tests and composites using harmonized data from two Wisconsin AD-risk-enriched cohorts.

INTRODUCTION: Published norms are typically cross-sectional and often are not sensitive to preclinical cognitive changes due to dementia. We developed and validated demographically adjusted cross-sectional and longitudinal normative standards using harmonized outcomes from two Alzheimer's disease (AD) risk-enriched cohorts. METHODS: Data from the Wisconsin Registry for Alzheimer's Prevention and the Wisconsin Alzheimer's Disease Research Center were combined. Quantile regression was used to develop unconditional (cross-sectional) and conditional (longitudinal) normative standards for 18 outcomes using data from cognitively unimpaired participants (N = 1390; mean follow-up = 9.25 years). Validity analyses (N = 2456) examined relationships between percentile scores (centiles), consensus-based cognitive statuses, and AD biomarker levels. RESULTS: Unconditional and conditional centiles were lower in those with consensus-based impairment or biomarker positivity. Similarly, quantitative biomarker levels were higher in those whose centiles suggested decline. DISCUSSION: This study presents normative standards for cognitive measures sensitive to pre-clinical changes. Future directions will investigate potential clinical applications of longitudinal normative standards. HIGHLIGHTS: Quantile regression was used to construct longitudinal norms for cognitive tests. Poorer percentile scores were related to concurrent diagnosis and Alzheimer's disease biomarkers. A ShinyApp was built to display test scores and norms and flag low performance.

Cross validation of the response bias scale and the response bias scale-19 in active-duty personnel: use on the MMPI-2-RF and MMPI-3.

The Response Bias Scale (RBS) is the central measure of cognitive over-reporting in the MMPI-family of instruments. Relative to other clinical populations, the research evaluating the detection of over-reporting is more limited in Veteran and Active-Duty personnel, which has produced some psychometric variability across studies. Some have suggested that the original scale construction methods resulted in items which negatively impact classification accuracy and in response crafted an abbreviated version of the RBS (RBS-19; Ratcliffe et al., 2022; Spencer et al., 2022). In addition, the most recent edition of the MMPI is based on new normative data, which impacts the ability to use existing literature to determine effective cut-scores for the RBS (despite all items having been retained across MMPI versions). To date, no published research exists for the MMPI-3 RBS. The current study examined the utility of the RBS and the RBS-19 in a sample of Active-Duty personnel (n = 186) referred for neuropsychological evaluation. Using performance validity tests as the study criterion, we found that the RBS-19 was generally equitably to RBS in classification. Correlations with other MMPI-2-RF over- and under-reporting symptom validity tests were slightly stronger for RBS-19. Implications and directions for research and practice with RBS/RBS-19 are discussed, along with implications for neuropsychological assessment and response validity theory.

Efficacy and safety of donepezil in patients with dementia with Lewy bodies: results from a 12-week multicentre, randomised, double-blind, and placebo-controlled phase IV study.

BACKGROUND: Donepezil has been approved in Japan for the treatment of dementia with Lewy bodies (DLB) based on clinical trials showing its beneficial effects on cognitive impairment. This phase IV study evaluated the efficacy of donepezil by focusing on global clinical status during a 12-week double-blind phase. METHODS: Patients with probable DLB were randomly assigned to the placebo (n = 79) or 10 mg donepezil (n = 81) groups. The primary endpoint was changes in global clinical status, assessed using the Clinician's Interview-Based Impression of Change plus Caregiver Input (CIBIC-plus). We also assessed four CIBIC-plus domains (general condition, cognitive function, behaviour, and activities of daily living) and changes in cognitive impairment and behavioural and neuropsychiatric symptoms measured using the Mini-Mental State Examination (MMSE) and the Neuropsychiatric Inventory (NPI), respectively. RESULTS: Although donepezil's superiority was not shown in the global clinical status, a significant favourable effect was detected in the cognitive domain (P = 0.006). MMSE scores improved in the donepezil group after adjustments in post hoc analysis (MMSE mean difference, 1.4 (95% confidence interval (CI), 0.42-2.30), P = 0.004). Improvements in NPIs were similar between the groups (NPI-2: -0.2 (95% CI, -1.48 to 1.01), P = 0.710; NPI-10: 0.1 (95% CI, -3.28 to 3.55), P = 0.937). CONCLUSION: The results support the observation that the efficacy of 10 mg donepezil in improving cognitive function is clinically meaningful in DLB patients. The evaluation of global clinical status might be affected by mild to moderate DLB patients enrolled in this study. No new safety concerns were detected.

Donepezil for dementia with Lewy bodies: meta-analysis of multicentre, randomised, double-blind, placebo-controlled phase II, III, and, IV studies.

BACKGROUND: Current evidence for the management of symptoms associated with dementia with Lewy bodies (DLB) using donepezil is limited. We conducted a meta-analysis of three randomised controlled trials of donepezil in patients with DLB to investigate the overall efficacy of donepezil on Mini-Mental State Examination (MMSE), Neuropsychiatric Inventory (NPI), and Clinician's Interview-Based Impression of Change-plus Caregiver Input (CIBIC-plus). METHODS: A meta-analysis was performed using the data of 312 patients administered placebo or 10 mg donepezil. Overall mean score differences for MMSE, NPI-2, and NPI-10 from baseline to week 12 and their 95% confidence intervals (CI) were estimated. For CIBIC-plus, which was transformed from a seven-point grade to a dichotomous outcome (improvements/no improvements), odds ratio (OR) and its 95% CI were estimated. Random-effects models were used, and heterogeneity was evaluated using the Cochrane's Q test and I2 statistic. RESULTS: Heterogeneity was suspected for NPI-2 (P < 0.05; I2 = 87.2%) and NPI-10 (P < 0.05; I2 = 67.7%) while it was not suspected for MMSE (P = 0.23; I2 = 32.4%) and CIBIC-plus (P = 0.26; I2 = 19.8%). The overall mean MMSE score difference (mean difference: 1.50; 95% CI, 0.67-2.34) and the overall odds of improving CIBIC-plus (OR: 2.20; 95% CI, 1.13-4.26) from baseline to week 12 were higher in the donepezil group than in the placebo group. CONCLUSION: Results of our meta-analysis indicated overall efficacy of donepezil on cognitive impairment and global clinical status in patients with DLB.

Interactive effects of hearing aid use and cognitive function in patients with hearing loss.

BACKGROUND: There has been a significant increase in scientific investigations of the hearing-dementia association among the research on potentially modifiable risk factors for cognitive impairment. We tested two clinical questions. Analysis 1: does persistent hearing aid (HA) use decrease the decline in cognitive function caused by ageing? Analysis 2: does cognitive function at the time of HA fitting predict future persistent HA use? METHODS: This case-control study performed at two referral centres reported data obtained over a 4.5-year period. We recruited a group of patients with cognitive decline, aged 65 or older with or without hearing loss. The intervention consisted of the use of HAs. The primary outcome measures were adherence to continuous HA use and cognitive function measured using the Japanese version of the Mini-Mental State Examination Test and the Reading Cognitive Test Kyoto. RESULTS: Eighteen HA users and 18 controls were included in the first analysis. HA use was associated with a deceleration of cognitive decline 12 months later. In the second analysis, 11 participants with good adherence to HA use were compared with 12 participants who showed poor adherence to HA use. Among the variables employed in this study, cognitive function measured using the Reading Cognitive Test Kyoto was significantly lower in participants with poor adherence to HA. CONCLUSIONS: HA use in cognitively impaired individuals with hearing loss can slow age-related cognitive decline. Cognitively impaired people with hearing loss who fail to commit to HA use tend to have lower cognitive measurement scores before HA fitting. HA use is generally more challenging as people age and their cognitive abilities decline. Therefore, it is desirable that HAs be used when hearing loss and dementia are in their early stages.

Impact of Acute Dopamine Replacement on Cognitive Function in Parkinson's Disease.

BACKGROUND: PD causes striatal dopaminergic denervation in a posterior/dorsal to anterior/ventral gradient, leaving motor and associative cortico-striato-pallido-thalamic loops differentially susceptible to hyperdopaminergic effects with treatment. As the choice and titration of symptomatic PD medications are guided primarily by motor symptoms, it is important to understand their cognitive implications. OBJECTIVE: To investigate the effects of acute dopaminergic medication administration on executive function in Parkinson's disease (PD). METHODS: Participants with idiopathic PD were administered the oral Symbol Digit Modalities Test (SDMT; n = 181) and the Stroop test (n = 172) in the off-medication and "best on" medication states. ANCOVA was used to test for differences between off-medication and on-medication scores corrected for age and years of education. RESULTS: After administration of symptomatic medications, scores worsened on the SDMT (F = 11.70, P < 0.001, d = -0.13), improved on the Stroop color (F = 26.89, P < 0.001, d = 0.184), word (F = 6.25, P = 0.013, d = 0.09), and color-word (F = 13.22, P < 0.001, d = 0.16) test components, and the Stroop difference and ratio-based interference scores did not significantly change. Longer disease duration correlated with lower scores on the SDMT, Stroop color, word, and color-word scores; however, longer disease duration and higher levodopa-equivalents correlated with higher Stroop difference-based interference scores. CONCLUSIONS: Symptomatic medication differentially affects performance on two cognitive tests in PD. After acute treatment, core Stroop measures improved, Stroop interference was unchanged, and SDMT performance worsened, likely reflecting complex changes in processing speed and executive function related to acute treatment. When considering motor symptom therapies in PD, an individual's cognitive demands and expectations, especially regarding executive function, should be considered.