Search Results (65)

Background/Objectives: We studied the possible protective effect of dietary curcumin in curry meals against cognitive decline and mild cognitive impairment (MCI) and dementia in a population-based Singapore Longitudinal Ageing cohort study. Methods: Baseline curry consumption frequency was categorized as five categories ranging from ‘never or rarely’ to ‘daily’. Among 2920 participants (mean age 65.5 ± SD 7.1 years) free of stroke, Parkinson’s disease, or traumatic brain injury at baseline, cognitive decline (MMSE drop ≥2) was assessed at 3–5 years (mean 4.5) follow-up. Occurrence of incident MCI-dementia was assessed at follow-up among 2446 participants without neurocognitive disorder at baseline. Results: A decreasing linear trend was observed between higher levels of curry consumption and cognitive decline (p = 0.037). The cumulative incidence of MCI-dementia decreased from 13.1% in those who never or rarely consumed curry to 3.6% in those who consumed curry daily (linear p < 0.001). The adjusted OR across levels of curry consumption exhibited a linear trend (p = 0.021) from OR = 0.61 (p < 0.05) for occasional consumption to OR = 0.21 (p < 0.001) for daily consumption. Conclusions: The intake of dietary curcumin through curry shows a dose-dependent reduction in incidence of cognitive decline and MCI-dementia in this Asian population of community-based elders. Full article

Background/Objectives: Neurocognitive disorders (NCDs) encompass a spectrum of conditions that significantly impact cognitive domains, including attention, memory, and language. Mild NCD, increasingly prevalent with aging, represents an early stage of these disorders, characterized by cognitive deficits that do not interfere with daily functioning. Non-pharmacological therapies, especially cognitive stimulation, are widely recommended to preserve cognitive function of older adults. This study aimed to evaluate the effectiveness of a 12-week individual cognitive stimulation (iCS) program on cognitive performance, mood, and prefrontal cortex activation in older adults with mild NCD using a single-blind, randomized, parallel two-arm RCT. Methods: A sample of 36 older adults were selected from a central region of Portugal. The intervention group (n = 18) received 24 iCS sessions, twice weekly for 12 weeks. The control group (n = 18) completed their regularly scheduled activities. Outcomes included global cognitive function, executive functioning, and mood. All participants were assessed at baseline and after the intervention. Functional near infra-red spectroscopy (fNIRS) was also collected to measure prefrontal cortex activity at both time points in the intervention group. Results: The intervention group showed a significant improvement in global cognition and executive functions, and reduced depressive symptomatology compared to the control group. fNIRS data revealed enhanced activation and functional efficiency in the lateral prefrontal cortex following the iCS program. Adherence and degree of collaboration to the intervention were very high. Conclusions: These findings suggest that iCS is an effective approach to improving cognitive function and mood in mildly cognitively impaired older adults. Full article

Background: The prevalence of HIV-associated neurocognitive disorders (HAND) remains high despite antiretroviral treatment (ART). Changes in gut microbiota and persistent immune activation have been suggested as possible causes, while the role of probiotic supplementation remains controversial. Methods: We included subjects with mild HAND and successful ART. They were randomized to receive either 6 months of high-dose probiotic supplementation or to continue with only ART. Immune activation markers and neuropsychological testing were performed at baseline and the end of follow-up. Neuropsychological testing assessed learning, episodic memory, attention/concentration, executive functions, language, information processing speed, and motor skills. Z- and T-scores were calculated for all domains but motor skills, allowing the measurement of the global deficit score (GDS). The trajectories of neuropsychological performances and immune activation markers were compared between groups. Results: From September 2020 to July 2021, 31 PWHs were included (median age 62, 73% men, CD4 744 cc/mm³), and 28 completed the 6-month follow-up. The characteristics of the subjects and their neuropsychological performance at baseline in the two groups were similar. At the end of follow-up, probiotics did not have any impact on immune activation markers, while they were associated with better improvement in GDS (T-score 0.0 in controls vs. −0.3 in probiotics, p = 0.048) and the attention/concentration test (Z-score 0.4 in controls vs. 1.2 in probiotics, p = 0.035). Conclusions: Oral supplementation with high-dose probiotics for 6 months did not affect systemic immune activation but was associated with improved neurocognitive performance, suggesting benefits from probiotic supplementation for mild HAND. Full article

Accelerated neurocognitive decline associated with surgeries under general anesthesia (GA), a phenomenon referred to as postoperative neurocognitive disorder (PND), is a significant public health concern. It not only poses inherent risks but may also contribute to the development of other neurodegenerative disorders. We systematically searched five databases for studies examining cognitive function in patients with mild-to-moderate TBI with (participant) or without (control) subsequent extracranial surgeries/GA. A random effects model was applied to calculate mean differences (MDs) and 95% confidence intervals (CIs). Five outcomes were analyzed post hoc: trail-making tests A and B (TMT-A/B), Glasgow Outcome Scale–Extended (GOSE), and length of stay (LOS) in intensive care units (ICUs) and hospitals. Five studies met the criteria for our meta-analysis. Patients with a history of mild-to-moderate TBI who underwent extracranial surgeries/GA exhibited worse outcomes in TMT-A [MD = 2.04; CI 0.38–3.70; p = 0.016] and TMT-B [MD = 16.59; CI 9.58–23.60; p < 0.001]. Differences in the ICU and hospital LOS and GOSE between the study groups were insignificant. Our results suggest that extracranial surgeries/GA may worsen neurocognitive outcomes without affecting functional recovery in mild-to-moderate TBI patients. Given the limited number of studies identified and the high incidence of TBI, more research on PND in TBI patients is warranted. Full article

Background: An increased risk of cognitive decline has been reported in patients with older age bipolar disorder (OABD); however, the underlying factors contributing to this association remain unclear. This cross-sectional study aims to identify the clinical features associated with cognitive impairment in OABD. Methods: A total of 152 participants, aged at least 50 years and diagnosed with bipolar disorder (BD) and related disorders in agreement with the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision criteria, were included in the study and divided into two subgroups based on the presence/absence of cognitive impairment, defined as a diagnosis of Mild Neurocognitive Disorder or Major Neurocognitive Disorder. Univariate comparisons and multivariate logistic regression models were performed to investigate the associations between clinical variables and cognitive impairment. Results: Cognitively impaired patients had a higher prevalence of otherwise specified BD/cyclothymic disorder, while BD type 2 was more common in the cognitively unimpaired group. Additionally, the cognitively impaired group had a later onset of major mood episodes (p < 0.05), fewer lifetime depressive episodes (p = 0.006), a higher prevalence of vascular leukoencephalopathy (p = 0.022) and dyslipidemia (p = 0.043), a lower prevalence of agoraphobia (p = 0.040), worse global functioning (p < 0.001), and higher psychopathology severity (p < 0.001). Late onset, vascular leukoencephalopathy, and dyslipidemia were all independently associated with cognitive impairment. Conclusions: Atypical BD, late onset of mood episodes, and somatic comorbidities like vascular leukoencephalopathy and dyslipidemia are associated with a higher risk of developing cognitive impairment and neurodegenerative disorders in OABD patients. Full article

Fragile-X-associated tremor/ataxia syndrome (FXTAS) is a progressive neurodegenerative disorder associated with the FMR1 gene premutation, characterized by the presence of 55 to 200 CGG triplet repeat expansions. Although the initial symptoms of FXTAS typically manifest in males around the age of 60 with motor symptoms and cognitive deficits, the presentation and progression in females differ. Women, in fact, exhibit a higher prevalence of neuropsychiatric symptoms, with an earlier onset compared to the motor symptoms observed in men. The following article reports on ten cases of women with a diagnosis of FMR1 gene premutation, originating from two medical centers. All the women in the study exhibited neuropsychiatric symptoms and subtle neurological signs as common features. Symptoms typically observed in the male population, such as tremors and cerebellar ataxia, were either absent or significantly reduced in the female cohort. Conversely, there was a higher prevalence of neuropsychiatric symptoms among the women. Neurocognitive impairment was only minimally evident, with mild executive dysfunction and memory complaints noted in a subset of cases. For this reason, we propose the terminology preFXTAS or prodromic FXTAS to define a clinical presentation in women characterized by early manifestations of FXTAS that do not entirely fulfill the established diagnostic criteria but exhibit MRI evidence of white matter alterations suggesting the initiation of the disease process. The study underscores the importance of establishing new diagnostic criteria for FXTAS and, at the same time, developing new biomarkers and interview checklists/assessment scales dedicated to females. Full article

Background: The Zika virus (ZIKV) is an arbovirus linked to “Congenital Zika Syndrome” and a range of neurodevelopmental disorders (NDDs), with microcephaly as the most severe manifestation. Milder NDDs, such as autism spectrum disorders and delays in neuropsychomotor and language development, often go unnoticed in neonates, resulting in long-term social and academic difficulties. Murine models of ZIKV infection can be used to mimic part of the spectrum of motor and cognitive deficits observed in humans. These can be evaluated through behavioral tests, enabling comparison with gene expression profiles and aiding in the characterization of ZIKV-induced NDDs. Objectives: This study aimed to identify genes associated with behavioral changes following a subtle ZIKV infection in juvenile BALB/c mice. Methods: Neonatal mice were subcutaneously inoculated with ZIKV (MH544701.2) on postnatal day 1 (DPN) at a dose of 6.8 × 10³ PFU. Viral presence in the cerebellum and cortex was quantified at 10- and 30-days post-infection (DPI) using RT-qPCR. Neurobehavioral deficits were assessed at 30 DPI through T-maze, rotarod, and open field tests. Next-Generation Sequencing (NGS) was performed to identify differentially expressed genes (DEGs), which were analyzed through Gene Ontology (GO) and KEGG enrichment. Gene interaction networks were then constructed to explore gene interactions in the most enriched biological categories. Results: A ZIKV infection model was successfully established, enabling brain infection while allowing survival beyond 30 DPI. The infection induced mild cognitive behavioral changes, though motor and motivational functions remained unaffected. These cognitive changes were linked to the functional repression of synaptic vesicles and alterations in neuronal structure, suggesting potential disruptions in neuronal plasticity. Conclusions: Moderate ZIKV infection with circulating strains from the 2016 epidemic may cause dysregulation of genes related to immune response, alterations in cytoskeletal organization, and modifications in cellular transport mediated by vesicles. Despite viral control, neurocognitive effects persisted, including memory deficits and anxiety-like behaviors, highlighting the long-term neurological consequences of ZIKV infection in models that show no apparent malformations. Full article

Background: Healthy cognitive functioning is a primary component of well-being, independence, and successful aging. Cognitive deficits can arise from various conditions, such as brain injury, mental illness, and neurological disorders. Rehabilitation is a highly specialized service limited to patients who have access to institutional settings. In response to this unmet need, telehealth solutions are ideal for triggering the migration of care from clinics to patients’ homes. Objectives: The aim of EARLY-COGN^3 will be threefold: (1) to test the efficacy of a digital health at-home intervention (tele@cognitive protocol) as compared to an unstructured cognitive at-home rehabilitation in a cohort of patients with Chronic Neurological Diseases (CNDs); (2) to investigate its effects on the biomolecular and neurophysiological marker hypothesizing that people with CNDs enrolled in this telerehabilitation program will develop changes in biological markers and cortical and subcortical patterns of connectivity; (3) to analyze potential cognitive, neurobiological, and neurophysiological predictors of response to the tele@cognitive treatment. Method: In this single-blind, randomized, and controlled pilot study, we will assess the short- and long-term efficacy of cognitive telerehabilitation protocol (tele@cognitive) as compared to an unstructured cognitive at-home rehabilitation (Active Control Group—ACG) in a cohort of 60 people with Mild Cognitive Impairment (MCI), Subjective Cognitive Complaints (SCCs), or Parkinson’s Disease (PD). All participants will undergo a clinical, functional, neurocognitive, and quality of life assessment at the baseline (T0), post-treatment (5 weeks, T1), and at the 3-month (T2) follow-up. Neurophysiological markers and biomolecular data will be collected at T0 and T1. Conclusions: EARLY-COGN^3 project could lead to a complete paradigm shift from the traditional therapeutic approach, forcing a reassessment on how CNDs could take advantage of a digital solution. (clinicaltrials.gov database, ID: NCT06657274) Full article

Background: Embodied cognition is an emerging concept in cognitive science that emphasizes the integral role of perception, action, and bodily experience in shaping human thought and understanding. Recently, a new instrument has been developed called the Automated Test of Embodied Cognition (ATEC), which provides a comprehensive measure of eight domains of embodied cognition. Method: An embodied cognition in an alcohol use disorder (AUD) sample (N = 49) was assessed using ATEC, which employs cognitively demanding physical tasks, like an exercise video, to measure executive functions (EFs), memory, and other cognitive processes “in action”. Results: Embodied delayed recall was the most frequent impairment (84%), and EF impairments were also common. Among the EF domains, self-regulation was the most frequently impaired at 43%. Using the ATEC total score, 43% of the sample were rated as having a mild or greater level of overall impairment. Strong support for concurrent validity was found for ATEC EF and memory domains when correlated with neurocognitive assessments conceptually related to them. Significant categorical agreement (impaired/not impaired) was also found between neurocognitive testing and ATEC total score. Using the ATEC total score, younger age, higher education, and better premorbid IQ were found to be potential protective factors against cognitive decline. Conclusions: Findings support ATEC’s potential for future studies related to AUD and other disorders that may lead to cognitive decline. Embodied cognition may provide new insights into how AUD affects cognition and functioning and be useful to determine what interventions may improve recovery. Full article

Postoperative neurocognitive disorder (PND) is a cognitive decline after general anesthesia and surgery, influenced by preexisting neurodegenerative conditions, stress, and inflammation. Traumatic brain injury (TBI) is linked to a dysregulated stress response, neuroinflammation, and cognitive issues. Patients with TBI often need extracranial surgeries under general anesthesia (GA), which can increase stress, neuroinflammation, and neurodegenerative changes, raising PND risk. We will search databases like Ovid Medline and Embase for studies on cognitive function in patients with mild to moderate TBI who had extracranial surgeries under general anesthesia (GA). Screening and data extraction will be done manually and with AI-assisted tools (ASReview). Study quality will be assessed using the Newcastle–Ottawa Scale. Statistical analyses will include mean differences, odds ratios, and meta-regression, addressing heterogeneity, sensitivity, and publication bias using Stata/SE. By meta-analyzing clinical studies, we aim to determine if TBI and GA/surgery interact to induce PND. We will use various data sources, subgroup analyses, sensitivity analyses, and meta-regression to assess factors like age, gender, and type of GA/surgery. This meta-analysis will enhance our understanding of PND risks, inform clinical practices, and highlight new research directions. The systematic review is registered in PROSPERO (CRD42024510980). Full article

Mild cognitive impairment (MCI) affects nearly 20% of older adults worldwide, with no targetable interventions for prevention. COVID-19 adversely affects cognition, with >70% of older adults with Long COVID presenting with cognitive complaints. Neurovascular coupling (NVC), an essential mechanism of cognitive function, declines with aging and is further attenuated in neurocognitive disorders. The effect of COVID-19 on NVC responses has yet to be addressed in older adults who are vulnerable to dementia progression. Participants with MCI and a history of COVID-19 (COV+, N = 31) and MCI participants with no history of infection (COV− N = 11) participated in this cross-sectional study to determine if COVID-19 affects cerebrocortical NVC responses and vascular function. Functional near-infrared spectroscopy was used to measure cerebrocortical NVC responses, and endothelial function was assessed via insonation of the brachial artery during a flow-mediated dilation protocol. NVC responses were elicited by the working memory n-back paradigm. NVC in the left dorsolateral prefrontal cortex and endothelial function was decreased in the COV+ group compared to the COV− group. These data provide mechanistic insight into how COVID-19 may exacerbate long-term cognitive sequela seen in older adults, highlighting the urgent need for further research and clinical trials to explore novel therapeutic interventions aimed at preserving/restoring NVC. Full article

Objective: Neurofilament light chain proteins (NfLs) are considered a promising biomarker of neuroaxonal damage in several neurological diseases. Their measurement in the serum and cerebrospinal fluid (CSF) of patients with dementia may be especially useful. Our aim was to compare the NfL measurement performance of two advanced technologies, specifically the Ella™ microfluidic platform and the Lumipulse™ fully automated system, in patients with cognitive disorders. Methods: Thirty subjects with neurodegenerative cognitive disorders (10 with Alzheimer’s Disease, 10 with Frontotemporal Dementia, and 10 with non-progressive Mild Cognitive Impairment) seen at the Cognitive Neurology Clinic of Modena University Hospital (Italy) underwent CSF and serum NfL measurement with both the Ella™ microfluidic platform (Bio-Techne, Minneapolis, MN, USA)) and the Lumipulse™ fully automated system for the CLEIA (Fujirebio Inc., Ghent, Belgium). Correlation and regression analyses were applied to assess the association between NfL concentrations obtained with the two assays in CSF and serum. The Passing–Bablok regression method was employed to evaluate the agreement between the assays. Results: There were high correlations between the two assays (r = 0.976, 95% CI. 0.950–0.989 for CSF vs. r = 0.923, 95% CI 0.842–0.964 for serum). A Passing–Bablok regression model was estimated to explain the relationship between the two assays, allowing us to switch from one to the other when only one assay was available. Conclusions: We found a good degree of correlation between the two methods in patients with neurocognitive disorders. We also established a method that will allow comparisons between results obtained with either technique, allowing for meta-analyses and larger sample sizes. Full article

Background: Neurocognitive disorders (NCDs) have a variable decline in cognitive function, while loneliness was associated with cognitive impairment and increased dementia risk. In the present study, we examined the associations of loneliness with functional and cognitive status in patients with minor (mild cognitive impairment) and major NCDs (dementia). Methods: We diagnosed mild NCD (n = 42) and major NCD (n = 164) through DSM-5 criteria on 206 participants aged > 65 years using the UCLA 3-Item Loneliness Scale (UCLA-3) to evaluate loneliness, the activities of daily living (ADL) and the instrumental activities of daily living (IADL) scales to measure functional status, and Mini-Mental State Examination (MMSE) to assess cognitive functions. Results: In a multivariate regression model, the effect of loneliness on cognitive functions was negative in major (β = −1.05, p < 0.0001) and minor NCD (β = −0.06, p < 0.01). In the fully adjusted multivariate regression model (sex–age–education–multimorbidity–depressive symptoms–antidementia drug treatment), the effect of loneliness remained negative for major NCD and became positive for minor NCD (β = 0.09, p < 0.001). The effect of loneliness on IADL (β = −0.26, p < 0.0001) and ADL (β = −0.24, p < 0.001) showed a negative effect for major NCD across the different models, while for minor NCD, the effect was positive (IADL: β = 0.26, p < 0.0001; ADL: β = 0.05, p = 0.01). Minor NCD displayed different levels of MMSE (β = 6.68, p < 0.001) but not ADL or IADL, compared to major NCD for the same levels of loneliness. MANOVA pill test suggested a statistically significant and different interactive effect of loneliness on functional and cognitive variables between minor and major NCDs. Conclusions: We confirmed the relationships between loneliness and cognitive and functional status in major NCD, observing a novel trend in minor NCD. Full article

Existing pharmacological treatments for mild neurocognitive disorder (NCD) offer limited effectiveness and adverse side effects. Transcranial pulse stimulation (TPS) utilizing ultrashort ultrasound pulses reaches deep brain regions and may circumvent conductivity issues associated with brain stimulation. This study addresses the gap in TPS research for mild NCD during a critical intervention period before irreversible cognitive degradation. Our objective was to explore the effectiveness and tolerability of TPS in older adults with mild NCD. In an open-label study, 17 older adults (including 10 females and 7 males) with mild NCD underwent TPS for two weeks with three sessions per week. Cognitive evaluations and fMRI scans were conducted pre- and post-intervention. The results indicated changes in functional connectivity in key brain regions, correlating with cognitive improvement at B = 0.087 (CI, 0.007–0.167; p = 0.038). However, cortical thickness measurements showed no significant differences. Here we show that TPS can enhance cognitive function within mild NCD. This proof-of-concept study suggests that TPS has potential as a non-invasive therapy used to attenuate cognitive decline, encouraging further investigation in larger randomized trials. The findings could influence clinical practice by introducing TPS as an adjunctive treatment option and potentially impact policy by promoting its inclusion in new treatment strategies for mild NCD. Full article

The world is aging and experiencing loneliness. Functional impairment in instrumental activities of daily living (IADL) in older people (OP) with mild neurocognitive disorder (MNCD) predicts loneliness. After the pandemic, there was an increase in perceived loneliness. We explored the association between loneliness, depression, deficits in IADL, and cognitive symptoms among OP. From February to December 2023, using a cross-sectional design, we interviewed probable cases with mild cognitive impairment and caregivers in two public facilities. We administered the UCLA Loneliness Scale v3, Lawton IADL Scale, Mini-Mental State Examination (MMSE), and Yesavage’s Geriatric Depression Scale. Samples were matched: 85 per group, 82.4% were women, married (52.95%), and mean age of 69.17 (±6.93) years. In our study, 30% displayed moderate to high levels of perceived loneliness. Multivariate analysis showed loneliness was associated with depression, low levels of IADL, and older age, but not with cognitive symptoms, which explained 22% of the total variance (F 165) = 16.99, (p < 0.001). Targeting symptoms and behaviors that could be modified (i.e., depression and functionality) can improve feelings of perceived loneliness and have an impact on morbidity and mortality with which it is associated. Full article