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.

Cognitive impairment, neurodegenerative disorders, and olfactory impairment: A literature review.

<br><b>Introduction:</b> The early detection and diagnosis of dementia are of key importance in treatment, slowing disease progression, or suppressing symptoms. The possible role of changes in the sense of smell is considered with regard to potential markers for early detection of Alzheimer's disease (AD).</br> <br><b>Materials and methods:</b> A literature search was conducted using the electronic databases PubMed, Scopus, and Web of Science between May 30, 2022 and August 2, 2022. The term "dementia" was searched with keyword combinations related to olfaction.</br> <br><b>Results:</b> A total of 1,288 records were identified through the database search. Of these articles, 49 were ultimately included in the analysis. The results showed the potential role of changes in the sense of smell as potential biomarkers for early detection of AD. Multiple studies have shown that olfactory impairment may be observed in patients with AD, PD, MCI, or other types of dementia. Even though smell tests are able to detect olfactory loss caused by neurodegenerative diseases, they cannot reliably distinguish between certain diseases.</br> <br><b>Conclusions:</b> In individuals with cognitive impairment or neurodegenerative diseases, olfactory assessment has repeatedly been reported to be used for early diagnosis, but not for differential diagnosis.</br>.

Biomarker profiling to determine clinical impact of microRNAs in cognitive disorders.

Alzheimer's disease (AD) and post-stroke cognitive impairment (PSCI) are the leading causes of progressive dementia related to neurodegenerative and cerebrovascular injuries in elderly populations. Despite decades of research, patients with these conditions still lack minimally invasive, low-cost, and effective diagnostic and treatment methods. MicroRNAs (miRNAs) play a vital role in AD and PSCI pathology. As they are easily obtained from patients, miRNAs are promising candidates for the diagnosis and treatment of these two disorders. In this study, we performed complete sequencing analysis of miRNAs from 24 participants, split evenly into the PSCI, post-stroke non-cognitive impairment (PSNCI), AD, and normal control (NC) groups. To screen for differentially expressed miRNAs (DE-miRNAs) in patients, we predicted their target genes using bioinformatics analysis. Our analyses identified miRNAs that can distinguish between the investigated disorders; several of them were novel and never previously reported. Their target genes play key roles in multiple signaling pathways that have potential to be modified as a clinical treatment. In conclusion, our study demonstrates the potential of miRNAs and their key target genes in disease management. Further in-depth investigations with larger sample sizes will contribute to the development of precise treatments for AD and PSCI.

Incidence and predictors of post-stroke cognitive impairment among patients admitted with first stroke at tertiary hospitals in Dodoma, Tanzania: A prospective cohort study.

INTRODUCTION: Stroke survivors develop cognitive impairment, which significantly impacts their quality of life, their families, and the community as a whole but not given attention. This study aims to determine the incidence and predictors of post-stroke cognitive impairment (PSCI) among adult stroke patients admitted to a tertiary hospital in Dodoma, Tanzania. METHODOLOGY: A prospective cohort study was conducted at tertiary hospitals in the Dodoma region, central Tanzania. A sample size of 158 participants with the first stroke confirmed by CT/MRI brain aged ≥ 18 years met the criteria. At baseline, social-demographic, cardiovascular risks and stroke characteristics were acquired, and then at 30 days, participants were evaluated for cognitive functioning using Montreal Cognitive Assessment (MoCA). Key confounders for cognitive impairment, such as depression and apathy, were evaluated using the Personal Health Questionnaire (PHQ-9) and Apathy Evaluation Scale (AES), respectively. Descriptive statistics were used to summarise data; continuous data were reported as Mean (SD) or Median (IQR), and categorical data were summarised using proportions and frequencies. Univariate and multivariable logistic regression analysis was used to determine predictors of PSCI. RESULTS: The median age of the 158 participants was 58.7 years; 57.6% of them were female, and 80.4% of them met the required criteria for post-stroke cognitive impairment. After multivariable logistic regression, left hemisphere stroke (AOR: 5.798, CI: 1.030-32.623, p = 0.046), a unit cm3 increase in infarct volume (AOR: 1.064, 95% CI: 1.018-1.113, p = 0.007), and apathy symptoms (AOR: 12.259, CI: 1.112-89.173, p = 0.041) had a significant association with PSCI. CONCLUSION: The study revealed a significant prevalence of PSCI; early intervention targeting stroke survivors at risk may improve their outcomes. Future research in the field will serve to dictate policies and initiatives.

The Neuroprotective Effect of Therapeutic Hypothermia in Cognitive Impairment of an Ischemia/Reperfusion Injury Mouse Model.

Background and Objectives: Therapeutic hypothermia (TH) shows promise as an approach with neuroprotective effects, capable of reducing secondary brain damage and intracranial pressure following successful mechanical thrombectomy in the acute phase. However, its effect on cognitive impairment remains unclear. This study investigated whether TH can improve cognitive impairment in a mouse model of transient middle cerebral artery occlusion followed by reperfusion (tMCAO/R). Materials and Methods: Nine-week-old C57BL/6N mice (male) were randomly assigned to three groups: sham, tMCAO/R, and tMCAO/R with TH. Cognitive function was assessed 1 month after model induction using the Y-maze test, and regional cerebral glucose metabolism was measured through positron emission tomography with fluorine-18 fluorodeoxyglucose. Results: tMCAO/R induced cognitive impairment, which showed improvement with TH. The TH group exhibited a significant recovery in cerebral glucose metabolism in the thalamus compared to the tMCAO/R group. Conclusions: These findings indicate that TH may hold promise as a therapeutic strategy for alleviating ischemia/reperfusion-induced cognitive impairment.

Cognitive Impairment following Mild Traumatic Brain Injury (mTBI): A Review.

Background: Mild Traumatic Brain Injury (mTBI) has been increasingly recognized as a public health concern due to its prevalence and potential to induce long-term cognitive impairment. We aimed to consolidate this observation by focusing on findings of neuropsychological assessments, neuroimaging, risk factors, and potential strategies for intervention to prevent and treat mTBI-associated cognitive impairments. Methods: A thorough search of PubMed, PsycINFO, and Embase databases was performed for studies published until 2024. Studies focusing on cognitive impairment after mTBI, with neurocognitive assessment as a primary outcome, were included. Results: We found consistent evidence of cognitive deficits, such as memory and attention impairments, and affected executive functions following mTBI. Neuroimaging studies corroborate these findings, highlighting structural and functional changes in the brain. Several risk factors for developing cognitive impairment post-mTBI were identified, including age, gender, genetics, and pre-existing mental health conditions. The efficacy of interventions, including cognitive rehabilitation and pharmaceutical treatment, varied across studies. Conclusions: Mild TBI can lead to significant long-term cognitive impairments, impacting an individual's quality of life. Further research is necessary to validate and standardize cognitive assessment tools post-mTBI, to elucidate the underlying neural mechanisms, and to optimize therapeutic interventions.

Demographic and Behavioral Risk Factors Predict Functional Limitations Associated with Subjective Cognitive Decline in Americans with Chronic Obstructive Pulmonary Disease: A Secondary Analysis.

Prior research indicates that subjective cognitive decline (SCD) affects approximately one-third of older adults with Chronic Obstructive Pulmonary Disease (COPD). However, there is limited population-based research on risk factors associated with SCD-related functional limitations within this vulnerable subgroup. A secondary data analysis of 2019 Behavioral Risk Factor Surveillance System data was conducted to address this gap, focusing on Americans ≥45 years old with COPD (N = 107,204). Several sociodemographic and health-related factors were independently associated with SCD-related functional limitations. Retired and unemployed individuals were significantly more likely to require assistance with day-to-day activities due to memory loss or confusion compared to employed individuals (AOR = 3.0, 95% CI: 1.2-8.0; AOR = 5.8, 95% CI: 3.01-1.5, respectively). Additionally, unemployed individuals were over five times more likely to report confusion or memory loss affecting social activities (AOR = 5.7, 95% CI: 2.9-11.0). Disparities were also observed among different racial groups, with Black/African Americans (AOR = 4.9, 95% CI: 2.3-10.4) and Hispanics (AOR = 2.4, 95% CI: 1.2-4.7) more likely than White and non-Hispanic people, respectively, to give up daily chores due to SCD. Our findings underscore the need for culturally sensitive interventions to address functional limitations faced by retired, unemployed, and minority adults with COPD and SCD.

Association of Vitamin D Levels with Risk of Cognitive Impairment and Dementia: A Systematic Review and Meta-Analysis of Prospective Studies.

Background: Emerging evidence suggests the potential relationship between vitamin D deficiency and risk of cognitive impairment or dementia. To what extent the excess risk of dementia conferred by vitamin D deficiency is less clear. Objective: We summarized the current evidence from several aspects and further quantified these associations. Methods: We collected relevant prospective cohort studies by searching PubMed, Embase and Cochrane up to July 2023. The pooled relative risks (RR) were evaluated by random-effects models. Dose-response analyses were conducted by the method of two-stage generalized least squares regression. Results: Of 9,267 identified literatures, 23 were eligible for inclusion in the meta-analyses, among which 9 and 4 literatures were included in the dose-response analyses for the risk of dementia and Alzheimer's disease (AD). Vitamin D deficiency exhibited a 1.42 times risk for dementia (95% confidence interval (CI) = 1.21-1.65) and a 1.57-fold excess risk for AD (95% CI = 1.15-2.14). And vitamin D deficiency was associated with 34% elevated risk with cognitive impairment (95% CI = 1.19-1.52). Additionally, vitamin D was non-linearly related to the risk of dementia (pnonlinearity = 0.0000) and AD (pnonlinearity = 0.0042). The approximate 77.5-100 nmol/L 25-hydroxyvitamin D [25(OH)D] was optimal for reducing dementia risk. And the AD risk seemed to be decreased when the 25(OH)D level >40.1 nmol/L. Conclusions: Vitamin D deficiency was a risk factor for dementia, AD, and cognitive impairment. The nonlinear relationships may further provide the optimum dose of 25(OH)D for dementia prevention.

Perspectives on the impact of vortioxetine on the treatment armamentarium of major depressive disorder.

INTRODUCTION: Major Depressive Disorder (MDD) is a mental health issue that significantly affects patients' quality of life and functioning. Despite available treatments, many patients continue to suffer due to incomplete symptom resolution and side effects. AREAS COVERED: This manuscript examines Vortioxetine's role in Major Depressive Disorder (MDD) treatment, highlighting its potential to reshape therapeutic strategies due to its unique Multimodal action and proven broad-spectrum efficacy in multiple depressive domains. A detailed examination of Vortioxetine's pharmacological aspects, including indications, dosage, pharmacodynamics, and pharmacokinetics, is provided, emphasizing its safety and effectiveness. The discussion extends to Vortioxetine's role in acute-phase treatment and maintenance of MDD and its profound impact on specialized depression domains. EXPERT OPINION: Vortioxetine is distinguished for its novel multimodal serotonin modulation mechanism, showcasing significant promise as an innovative treatment for MDD. Its efficacy, which is dose-dependent, along with a commendable tolerability profile, positions it as a potential leading option for initial treatment strategies. The discourse on dosage titration, particularly the strategy of initiating treatment at lower doses followed by gradual escalation, underscores the approach toward minimizing initial adverse effects while optimizing therapeutic outcomes, aligning with the principles of personalized medicine in psychiatric care.

Impact of Type 2 Diabetes and Glycated Hemoglobin Levels Within the Recommended Target Range on Mortality in Older Adults With Cognitive Impairment Receiving Care at a Memory Clinic: NCGG-STORIES.

OBJECTIVE: To determine the impact of type 2 diabetes and glycated hemoglobin (HbA1c) levels within the recommended target range according to the Japan Diabetes Society/Japan Geriatrics Society Joint Committee on mortality in older adults with cognitive impairment. RESEARCH DESIGN AND METHODS: This retrospective cohort study included 1,528 and 468 patients aged ≥65 years without and with type 2 diabetes, respectively, who were visiting a memory clinic. The 468 patients with type 2 diabetes were divided into three groups (within, above, and below the target range) based on their HbA1c levels, cognitive function, ability to perform activities of daily living, and medications associated with a high risk of hypoglycemia. The impact of diabetes and HbA1c levels on mortality was evaluated using Cox proportional hazards models. RESULTS: Over a median follow-up period of 3.8 years, 353 patients (17.7%) died. Compared with individuals without type 2 diabetes, HbA1c levels above (hazard ratio [HR] 1.70, 95% CI 1.08-2.69) and below (HR 2.15, 95% CI 1.33-3.48) the target range were associated with a higher risk of death; however, HbA1c levels within the target range were not (HR 1.02, 95% CI 0.77-1.36). CONCLUSIONS: HbA1c levels above and below the target range were associated with a higher risk of mortality, whereas patients with HbA1c levels within the target range did not exhibit a higher risk of mortality than individuals without type 2 diabetes. These results provide empirical support for the current target ranges among older adults with cognitive impairment.

Deciphering the dual role of N-methyl-D-Aspartate receptor in postoperative cognitive dysfunction: A comprehensive review.

Postoperative cognitive dysfunction (POCD) is a common complication following surgery, adversely impacting patients' recovery, increasing the risk of negative outcomes, prolonged hospitalization, and higher mortality rates. The N-methyl-D-aspartate (NMDA) receptor, crucial for learning, memory, and synaptic plasticity, plays a significant role in the development of POCD. Various perioperative factors, including age and anesthetic use, can reduce NMDA receptor function, while surgical stress, inflammation, and pain may lead to its excessive activation. This review consolidates preclinical and clinical research to explore the intricate relationship between perioperative factors affecting NMDA receptor functionality and the onset of POCD. It discusses the influence of aging, anesthetic administration, perioperative injury, pain, and inflammation on the NMDA receptor-related pathophysiology of POCD. The comprehensive analysis presented aims to identify effective treatment targets for POCD, contributing to the improvement of patient outcomes post-surgery.

Cognition in older age bipolar disorder: An analysis of archival data across the globe.

BACKGROUND: Cognitive deficits in bipolar disorder (BD) impact functioning and are main contributors to disability in older age BD (OABD). We investigated the difference between OABD and age-comparable healthy comparison (HC) participants and, among those with BD, the associations between age, global cognitive performance, symptom severity and functioning using a large, cross-sectional, archival dataset harmonized from 7 international OABD studies. METHODS: Data from the Global Aging and Geriatric Experiments in Bipolar Disorder (GAGE-BD) database, spanning various standardized measures of cognition, functioning and clinical characteristics, were analyzed. The sample included 662 euthymic to mildly symptomatic participants aged minimum 50years (509 BD, 153 HC), able to undergo extensive cognitive testing. Linear mixed models estimated associations between diagnosis and global cognitive performance (g-score, harmonized across studies), and within OABD between g-score and severity of mania and depressive symptoms, duration of illness and lithium use and of global functioning. RESULTS: After adjustment for study cohort, age, gender and employment status, there was no significant difference in g-score between OABD and HC, while a significant interaction emerged between employment status and diagnostic group (better global cognition associated with working) in BD. Within OABD, better g-scores were associated with fewer manic symptoms, higher education and better functioning. LIMITATIONS: Cross-sectional design and loss of granularity due to harmonization. CONCLUSION: More research is needed to understand heterogenous longitudinal patterns of cognitive change in BD and understand whether particular cognitive domains might be affected in OABD in order to develop new therapeutic efforts for cognitive dysfunction OABD.

Neopterin, kynurenine metabolites, and indexes related to vitamin B6 are associated with post-stroke cognitive impairment: The Nor-COAST study.

BACKGROUND AND AIMS: We have previously shown that systemic inflammation was associated with post-stroke cognitive impairment (PSCI). Because neopterin, kynurenine pathway (KP) metabolites, and B6 vitamers are linked to inflammation, in our study we investigated whether those biomarkers were associated with PSCI. MATERIAL AND METHODS: The Norwegian Cognitive Impairment After Stroke study is a prospective multicenter cohort study of patients with acute stroke recruited from May 2015 through March 2017. Plasma samples of 422 participants (59 % male) with ischemic stroke from the index hospital stay and 3 months post-stroke were available for analyses of neopterin, KP metabolites, and B6 vitamers using liquid chromatography-tandem mass spectrometry. Mixed linear regression analyses adjusted for age, sex, and creatinine, were used to assess whether there were associations between those biomarkers and cognitive outcomes, measured by the Montreal Cognitive Assessment scale (MoCA) at 3-, 18-, and 36-month follow-up. RESULTS: Participants had a mean (SD) age of 72 (12) years, with a mean (SD) National Institutes of HealthStroke Scale score of 2.7 (3.6) at Day 1. Higher baseline values of quinolinic acid, PAr (i.e., an inflammatory marker based on vitamin B6 metabolites), and HKr (i.e., a marker of functional vitamin B6 status based on selected KP metabolites) were associated with lower MoCA score at 3, 18, and 36 months post-stroke (p < 0.01). Higher baseline concentrations of neopterin and 3-hydroxykynurenine were associated with lower MoCA scores at 18 and 36 months, and higher concentrations of xanthurenic acid were associated with higher MoCA score at 36 months (p < 0.01). At 3 months post-stroke, higher concentrations of neopterin and lower values of pyridoxal 5́-phosphate were associated with lower MoCA scores at 18- and 36-month follow-up, while lower concentrations of picolinic acid were associated with a lower MoCA score at 36 months (p < 0.01). CONCLUSION: Biomarkers and metabolites of systemic inflammation, including biomarkers of cellular immune activation, indexes of vitamin B6 homeostasis, and several neuroactive metabolites of the KP pathway, were associated with PSCI. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02650531.

Use of Lecanemab for Patients With Cardiovascular Disease: The Challenge of Uncertainty.

This Viewpoint discusses lecanemab use and the risk of cerebral macrohemorrhage for patients with mild cognitive impairment or early dementia.

Development and validation of cognitive ageing risk score (CARS) for early detection of subtle cognitive deficits in older people.

BACKGROUND: Early cognitive deficits commonly seen in older people have not been well defined and managed in primary care. The objectives are (1) to develop and validate a new risk score to estimate the risk of dementia in Chinese older population; and (2) to evaluate the use of risk score in conjunction with cognitive screening in detecting early cognitive deficits in community older people. METHODS: A development cohort of 306 cognitive healthy older adults aged 60 or above were followed for 6 years. A CARS was constructed using the estimated coefficients of risk factors associated with dementia at follow up. Validation was carried out in another five-year cohort of 383 older adults. The usefulness of CARS in detecting early cognitive deficits was evaluated. RESULTS: Risk factors include older age, male gender, low level of education, poorly controlled diabetes, prolonged sleep latency, fewer mind body or light exercise, loneliness, and being apolipoprotein e4 carriers. A cutoff of CARS at -1.3 had a sensitivity of 83.9% and a specificity of 75.4% to predict dementia. The area under curve was 82.5% in the development cohort. Early cognitive deficits were characterized by impaired retention (p <.001, 95% CI 0.2-0.9) and attention (p =.012, 95% CI 0.1-0.8). CONCLUSION: The CARS can be used as a standard risk assessment of dementia or in conjunction with a computerized cognitive screening to evaluate a full cognitive profile for detecting early cognitive deficits. The result put forward the integration of risk algorithm into smart healthcare system to provide personalized lifestyle interventions.

Prevalence of fatigue and cognitive impairment after traumatic brain injury.

BACKGROUND: Following traumatic brain injury (TBI) some patients develop lingering comorbid symptoms of fatigue and cognitive impairment. The mild cognitive impairment self-reported by patients is often not detected with neurocognitive tests making it difficult to determine how common and severe these symptoms are in individuals with a history of TBI. This study was conducted to determine the relative prevalence of fatigue and cognitive impairment in individuals with a history of TBI. METHODS: The Fatigue and Altered Cognition Scale (FACs) digital questionnaire was used to assess self-reported fatigue and cognitive impairment. Adults aged 18-70 were digitally recruited for the online anonymous study. Eligible participants provided online consent, demographic data, information about lifetime TBI history, and completed the 20 item FACs questionnaire. RESULTS: A total of 519 qualifying participants completed the online digital study which included 204 participants with a history of TBI of varied cause and severity and 315 with no history of TBI. FACs Total Score was significantly higher in the TBI group (57.7 ± 22.2) compared to non-TBI (39.5 ± 23.9; p<0.0001) indicating more fatigue and cognitive impairment. When stratified by TBI severity, FACs score was significantly higher for all severity including mild (53.9 ± 21.9, p<0.0001), moderate (54.8 ± 24.4, p<0.0001), and severe (59.7 ± 20.9, p<0.0001) TBI. Correlation analysis indicated that more severe TBI was associated with greater symptom severity (p<0.0001, r = 0.3165). Ancillary analysis also suggested that FACs scores may be elevated in participants with prior COVID-19 infection but no history of TBI. CONCLUSIONS: Adults with a history of even mild TBI report significantly greater fatigue and cognitive impairment than those with no history of TBI, and symptoms are more profound with greater TBI severity.

Brain Age Is Associated with Cognitive Outcomes of Cholinesterase Inhibitor Treatment in Patients with Mild Cognitive Impairment.

Background: The effect of cholinesterase inhibitor (ChEI) on mild cognitive impairment (MCI) is controversial. Brain age has been shown to predict Alzheimer's disease conversion from MCI. Objective: The study aimed to show that brain age is related to cognitive outcomes of ChEI treatment in MCI. Methods: Brain MRI, the Clinical Dementia Rating (CDR) and Mini-Mental State Exam (MMSE) scores were retrospectively retrieved from a ChEI treatment database. Patients who presented baseline CDR of 0.5 and received ChEI treatment for at least 2 years were selected. Patients with stationary or improved cognition as verified by the CDR and MMSE were categorized to the ChEI-responsive group, and those with worsened cognition were assigned to the ChEI-unresponsive group. A gray matter brain age model was built with a machine learning algorithm by training T1-weighted MRI data of 362 healthy participants. The model was applied to each patient to compute predicted age difference (PAD), i.e. the difference between brain age and chronological age. The PADs were compared between the two groups. Results: 58 patients were found to fit the ChEI-responsive criteria in the patient data, and 58 matched patients that fit the ChEI-unresponsive criteria were compared. ChEI-unresponsive patients showed significantly larger PAD than ChEI-responsive patients (8.44±8.78 years versus 3.87±9.02 years, p = 0.0067). Conclusions: Gray matter brain age is associated with cognitive outcomes after 2 years of ChEI treatment in patients with the CDR of 0.5. It might facilitate the clinical trials of novel therapeutics for MCI.

An Examination of Cognitive Heterogeneity in Parkinson Disease: The Dual-Syndrome Hypothesis.

PURPOSE: Cognitive impairment is one of the most debilitating nonmotor symptoms in Parkinson disease (PD), and its presentation is heterogeneous. One proposed model to explain cognitive variability in PD is the dual-syndrome hypothesis. This hypothesis delineates two cognitive profiles, a "fronto-striatal" profile and a "posterior cortical" profile according to symptom presentation, associated motor phenotype, and risk for dementia. The current study examined the dual-syndrome hypothesis in individuals with idiopathic PD to evaluate the existence of these profiles, determine the association with the motor phenotype (tremor dominant vs. postural instability/gait disorder), and assess the relative risk for dementia. METHOD: A retrospective examination was conducted using data from the Parkinson's Progression Markers Initiative database at baseline (within 2 years of diagnosis) and 5 years after baseline. Descriptive categorizations, cluster analyses, generalized linear mixed models, and logistic regressions were used to address the research questions. RESULTS: There was emerging evidence of cognitive profiles; however, these were not fully supported by cluster analyses. Baseline cognitive profile was associated with later motor phenotype, and as predicted, dementia risk was greatest in persons with baseline posterior cortical impairments. CONCLUSION: The current results provide mixed support for the dual-syndrome hypothesis, with some evidence that the posterior cortical cognitive profile is associated with postural instability and gait disorder as well as greater dementia risk.

Impaired olfactory identification in dementia-free individuals is associated with the functional abnormality of the precuneus.

OBJECTIVE: Olfactory dysfunction indicates a higher risk of developing dementia. However, the potential structural and functional changes are still largely unknown. METHODS: A total of 236 participants were enrolled, including 45 Alzheimer's disease (AD) individuals and 191dementia-free individuals. Detailed study methods, comprising neuropsychological assessment and olfactory identification test (University of Pennsylvania smell identification test, UPSIT), as well as structural and functional magnetic resonance imaging (MRI) were applied in this research. The dementia-free individuals were divided into two sub-groups based on olfactory score: dementia-free with olfactory dysfunction (DF-OD) sub-group and dementia-free without olfactory dysfunction (DF-NOD) sub-group. The results were analyzed for subsequent intergroup comparisons and correlations. The cognitive assessment was conducted again three years later. RESULTS: (i) At dementia-free stage, there was a positive correlation between olfactory score and cognitive function. (ii) In dementia-free group, the volume of crucial brain structures involved in olfactory recognition and processing (such as amygdala, entorhinal cortex and basal forebrain volumes) are positively associated with olfactory score. (iii) Compared to the DF-NOD group, the DF-OD group showed a significant reduction in olfactory network (ON) function. (iv) Compared to DF-NOD group, there were significant functional connectivity (FC) decline between PCun_L(R)_4_1 in the precuneus of posterior default mode network (pDMN) and the salience network (SN) in DF-OD group, and the FC values decreased with falling olfactory scores. Moreover, in DF-OD group, the noteworthy reduction in FC were observed between PCun_L(R)_4_1 and amygdala, which was a crucial component of ON. (v) The AD conversion rate of DF-OD was 29.41%, while the DF-NOD group was 12.50%. The structural and functional changes in the precuneus were also observed in AD and were more severe. CONCLUSIONS: In addition to the olfactory circuit, the precuneus is a critical structure in the odor identification process, whose abnormal function underlies the olfactory identification impairment of dementia-free individuals.

Frailty and Cognitive Function in Middle-Aged and Older Adults With Congenital Heart Disease.

BACKGROUND: Life expectancy of patients with congenital heart disease (CHD) has increased rapidly, resulting in a growing and aging population. Recent studies have shown that older people with CHD have higher morbidity, health care use, and mortality. To maintain longevity and quality of life, understanding their evolving medical and psychosocial challenges is essential. OBJECTIVES: The authors describe the frailty and cognitive profile of middle-aged and older adults with CHD to identify predictor variables and to explore the relationship with hospital admissions and outpatient visits. METHODS: Using a cross-sectional, multicentric design, we included 814 patients aged ≥40 years from 11 countries. Frailty phenotype was determined using the Fried method. Cognitive function was assessed by the Montreal Cognitive Assessment. RESULTS: In this sample, 52.3% of patients were assessed as robust, 41.9% as prefrail, and 5.8% as frail; 38.8% had cognitive dysfunction. Multinomial regression showed that frailty was associated with older age, female sex, higher physiologic class, and comorbidities. Counterintuitively, patients with mild heart defects were more likely than those with complex lesions to be prefrail. Patients from middle-income countries displayed more prefrailty than those from higher-income countries. Logistic regression demonstrated that cognitive dysfunction was related to older age, comorbidities, and lower country-level income. CONCLUSIONS: Approximately one-half of included patients were (pre-)frail, and more than one-third experienced cognitive impairment. Frailty and cognitive dysfunction were identified in patients with mild CHD, indicating that these concerns extend beyond severe CHD. Assessing frailty and cognition routinely could offer valuable insights into this aging population.