Impairment In Cognitive Domains Research Articles

Longitudinal trajectory effects of different MCI subtypes on general cognitive and daily functions in a population-based cohort of older adults

ObjectivesTo identify different mild cognitive impairment (MCI) phenotypes based on substantial relative impairment in specific cognitive domains and then characterize the complex process of general cognitive and daily functions over time in older adults with these MCI subtypes. MethodsA total of 1020 participants with MCI at baseline from the Alzheimer's Disease Neuroimaging Initiative (ADNI) were recruited. MCI subtypes were obtained based on neuropsychological tests in five cognitive domains: memory (M), visuospatial function (V), language (L), processing speed (P), and executive function (E). General cognitive function and daily function were measured by the Mini-Mental State Examination (MMSE) and the Functional Assessment Questionnaire (FAQ), respectively. Linear mixed models were fitted to curve their trajectories across different MCI subtypes. ResultsConsidering visuospatial function, subtypes were MO (memory impaired only), M&V (memory and visuospatial function impaired) and M&nV (memory impaired and visuospatial function non-impaired). Similar subtypes and naming rules were obtained based on language, executive function, and processing speed. Further, depending on the number of relative impaired cognitive domains M&S and M&M were obtained. Participants with MO had the highest prevalence in the sample (53.4 %), followed by M&nV (31.1 %). Participants with M&V had the highest mean age (74.69 years) at baseline and the greatest dementia conversion rate (53.2 %). The MMSE and FAQ score trajectories changed most slowly in participants with MO while fastest in those with M&V. Obvious different trajectories of both MMSE and FAQ scores were observed across different subtypes based on visuospatial function and executive function. ConclusionCompared to MO, individuals with multi-dimensional cognitive impairment have worse general cognitive and daily functions, especially for those with M&V.

Moving on with (social) cognition in idiopathic cervical dystonia.

Cervical dystonia (CD) is a movement disorder characterized by involuntary muscle contractions causing sustained twisting movements and abnormal postures of the neck and head. Assumed affected neuronal regions are the cortico-striatal-thalamo-cortical circuits, which are also involved in cognitive functioning. Indeed, impairments in different cognitive domains have been found in CD patients. However, to date studies have only investigated a limited range of cognitive functions within the same sample. In particular, social cognition (SC) is often missing from study designs. Hence, we aimed to evaluate a broad range of cognitive functions including SC in CD patients. In the present study 20 idiopathic CD patients and 40 age-, gender-, and IQ-matched healthy controls (HCs) were assessed with tests for non-SC (verbal memory, psychomotor speed, and executive functions) as well as for SC (emotion recognition, Theory of Mind (ToM), and empathy). CD patients scored on average significantly lower than HC on tests for non-SC, but did not show impairments on any of the tests for SC. The current study showed impairments in non-SC in CD, but intact social cognitive functions. These results underline the importance of recognizing non-motor symptoms in idiopathic CD patients, but emphasize a focus on identifying strengths and weaknesses in cognitive functioning as these influence daily life activities.

MoCA Domain-Specific Pattern of Cognitive Impairment in Stroke Patients Attending Intensive Inpatient Rehabilitation: A Prospective Study.

A domain-specific perspective to cognitive functioning in stroke patients may predict their cognitive recovery over time and target stroke rehabilitation intervention. However, data about domain-specific cognitive impairment after stroke are still scarce. This study prospectively investigated the domain-specific pattern of cognitive impairments, using the classification proposed by the Montreal Cognitive Assessment (MoCA), in a cohort of 49 stroke patients at admission (T0), discharge (T1), and six-month follow-up (T2) from subacute intensive rehabilitation. The predictive value of T0 cognitive domains cognitive impairment at T1 and T2 was also investigated. Patients' cognitive functioning at T0, T1, and T2 was assessed through the MoCA domains for executive functioning, attention, language, visuospatial, orientation, and memory. Different evolutionary trends of cognitive domain impairments emerged across time-points. Patients' impairments in all domains decreased from T0 to T1. Attention and executive impairments decreased from T0 to T2 (42.9% and 26.5% to 10.2% and 18.4%, respectively). Conversely, altered visuospatial, language, and orientation increased between T1 and T2 (16.3%, 36.7%, and 40.8%, respectively). Additionally, patients' global cognitive functioning at T1 was predicted by the language and executive domains in a subacute phase (p = 0.031 and p = 0.001, respectively), while in the long term, only attention (p = 0.043) and executive (p = 0.019) domains intervened. Overall, these results confirm the importance of a domain-specific approach to target cognitive recovery across time in stroke patients.

Red Cell Distribution Width is Related to Mild Cognitive Impairment: A Cross-Sectional Study of Community Residents.

Previous literature has reported that red cell distribution width (RDW) correlated with Alzheimer's disease (AD), but the correlation with mild cognitive impairment (MCI) was not clear. This study aimed to investigate MCI in the residents aged ≥65 living in the suburban of Shanghai, China. A total of 550 participants were recruited as MCI (MCI group, 226) and normal (NC group, 284) groups and received blood examination voluntarily. Blood routine indexes were tested by blood tests using Sysmex XT-4000i (Japan). The Chi-square test, t-test, and linear regression analysis were used to find the statistical difference and correlation of data, respectively. Each cognition domain of MCI was found to be impaired, the weight of which, however, was different in integral damage. Most MCI people had impairment of attention among cognitive domains (235, 88.3%). According to the results of the binary logistic regression, the highest weight among impaired cognitive domains was for attention in MCI, and the Wald value of attention was higher than those of others (Wald = 51.83). Additionally, RDW had the greatest negative correlation with attention score (P < 0.05). Increased RDW may be considered as a biomarker of MCI.

Evolving trends in neuropsychological profiles of post COVID-19 condition: A 1-year follow-up in individuals with cognitive complaints.

Cognitive difficulties are reported as lasting sequelae within post COVID-19 condition. However, the chronicity of these difficulties and related factors of fatigue, mood, and perceived health have yet to be fully determined. To address this, the current longitudinal study aimed to clarify the trends of cognitive test performance and cognitive domain impairment following COVID-19 onset, and whether hospitalization influences outcomes. 57 participants who reported subjective cognitive difficulties after confirmed COVID-19 infection were assessed at baseline (~6 months post COVID-19) and follow-up (~15 months later) visits. Assessments included measures across multiple cognitive domains and self-report questionnaires of fatigue, mood, and overall health. Analyses were conducted in three stages: at the test score level (raw and adjusted scores), at the cognitive domain level, and stratified by hospitalization status during infection. Results at the test-score level indicate that cognitive performance remains relatively stable across assessments at the group level, with no significant improvements in any adjusted test scores at follow-up. Cognitive domain analyses indicate significant reductions in attention and executive functioning impairment, while memory impairment is slower to resolve. On self-report measures, there was a significant improvement in overall health ratings at follow-up. Finally, those hospitalized during infection performed worse on timed cognitive measures across visits and accounted for a larger proportion of cases with short-term and working memory impairment at follow-up. Overall, our findings indicate that cognitive difficulties persist both at test score and cognitive domain levels in many cases of post COVID-19 condition, but evidence suggests some improvement in global measures of attention, executive functioning and overall self-rated health. Furthermore, an effect of hospitalization on cognitive symptoms post COVID-19 may be more discernible over time.

Emotion regulation and executive functions in young and older Brazilian adults

Introduction/objective: The healthy aging process involves changes in neurobiological functions at various levels and is associated with a slight impairment in various cognitive domains, such as executive functions (EF), as well as the enhancement of emotional skills. The objective of this study was to compare the use of emotion regulation (ER) strategies in young adults (YA) and older adults (OA) and explore the association between ER skills and EF between age groups. Method: Participants were 40 YA between 18 and 39 years of age (50% women) and 40 OA &gt; 60 years old (50% women), residents in the Federal District, Brazil. Phonological Verbal Fluency (FAS), semantic and switching (animals and fruits) and action tests were administered, along with the Stroop Test. Results: There was a statistically significant correlation of the Cognitive Reappraisal (CR) strategy and both semantic and switching verbal fluency tests in YA, and between the CR strategy and the FAS test and the Stroop Test in OA. That is, executive performance showed a direct relationship with ER in both groups, with greater use of cognitive reappraisal by older adults. Conclusions: The results of this study highlight the relevance of continuing to investigate the relationship between these abilities and analysing in greater depth their alterations during the aging process.

Vortioxetine Reverses Impairment of Visuospatial Memory and Cognitive Flexibility Induced by Degarelix as a Model of Androgen Deprivation Therapy in Rats

Introduction: Androgen deprivation therapy (ADT) is a mainstay treatment for prostate cancer, but many patients experience cognitive impairment in domains mediated by the medial prefrontal cortex (mPFC) and hippocampus. Prostate cancer typically occurs in older patients (>65 years). As age is often accompanied by cognitive decline, it may impact the efficacy of any treatment aimed at restoring cognitive impairment induced by ADT. Vortioxetine, a multimodal antidepressant that improves cognition in depression, has been shown to be efficacious in elderly patients. Therefore, vortioxetine may improve cognition in older patients who experience cognitive decline after ADT. Methods: Young (3 months) and middle-aged (13 months) rats were used to investigate the influence of age on treating ADT-induced cognitive decline. As our previous studies used surgical castration, we tested if vortioxetine would reverse cognitive deficits associated with more translationally relevant chemical castration using degarelix. Vortioxetine was given in the diet for 21 days. Animals underwent behavioral testing to assess visuospatial memory mediated by the hippocampus and cognitive flexibility mediated by the mPFC. We also investigated changes in afferent-evoked responses in these regions in middle-aged rats. Results: Degarelix induced impairments in both visuospatial memory and cognitive flexibility that were reversed by vortioxetine. Vortioxetine also rescued afferent-evoked responses in the mPFC and hippocampus. However, modest age-related reductions in baseline visuospatial memory limited our ability to detect further decreases induced by degarelix in middle-aged rats due to a floor effect. Conclusion: These results suggest that vortioxetine may be a treatment option for older prostate cancer patients who experience cognitive decline after ADT.

Cognitively defined Alzheimer's dementia subgroups have distinct atrophy patterns.

We sought to determine structural magnetic resonance imaging (MRI) characteristics across subgroups defined based on relative cognitive domain impairments using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and to compare cognitively defined to imaging-defined subgroups. We used data from 584 people with Alzheimer's disease (AD) (461 amyloid positive, 123 unknown amyloid status) and 118 amyloid-negative controls. We used voxel-based morphometry to compare gray matter volume (GMV) for each group compared to controls and to AD-Memory. There was pronounced bilateral lower medial temporal lobe atrophy with relative cortical sparing for AD-Memory, lower left hemisphere GMV for AD-Language, anterior lower GMV for AD-Executive, and posterior lower GMV for AD-Visuospatial. Formal asymmetry comparisons showed substantially more asymmetry in the AD-Language group than any other group (p=1.15×10-10 ). For overlap between imaging-defined and cognitively defined subgroups, AD-Memory matched up with an imaging-defined limbic predominant group. MRI findings differ across cognitively defined AD subgroups.

Comparison of clinicopathologic features of Limbic and Diffuse Transactive Response DNA‐binding Protein 43 pathology in Alzheimer’s disease neuropathologic spectrum

AbstractBackgroundIncreasing evidence suggests that transactive response DNA‐binding protein 43 (TDP‐43) pathology in Alzheimer’s Disease (AD), or AD‐TDP, can be diffuse or limbic‐predominant. Understanding whether diffuse AD‐TDP has genetic, clinical, and pathological features that differ from limbic AD‐TDP could have clinical and research implications. We aimed to better characterize the clinicopathologic features of diffuse AD‐TDP and differentiate it from limbic‐predominant AD‐TDP pathology.MethodThree hundred sixty‐three participants were prospectively recruited and followed in the Mayo Clinic Study of Aging, Alzheimer’s Disease Research Center, and Neurodegenerative Research Group and died between May 1999 and August 2021. All underwent genetic, clinical, neuropsychologic, and neuropathologic evaluations. At postmortem evaluation, they showed Alzheimer’s disease neuropathologic changes and TDP‐43‐immunoreactive inclusions. The distribution of TDP‐43 pathology was assessed using the Josephs 6‐stage scheme. Participants with TDP‐43 stages 1‐3 were classified as Limbic, while those with stages 4‐6 were classified as Diffuse. Neuropathologically defined frontotemporal lobar degeneration cases were excluded. Multivariable logistic regression was used to identify clinicopathological features that predicted diffuse TDP‐43 pathology at postmortem. We hypothesized that the Diffuse group would show impairment in cognitive domains beyond episodic memory and more hippocampal sclerosis.ResultsThe cohort was 61% female and old at onset (median:76 years [IQR:70‐82]) and death (median:88 years [IQR:82‐92]). Fifty‐four percent (n = 197) were classified as Limbic and 46% (n = 166) as Diffuse. A “clinical” multivariate logistic regression fit to 85 participants with all clinical variables of interest showed that later age at onset (OR:1.09, 95%CI:1.01‐1.19;P = 0.03), longer disease duration (OR:1.17, 95%CI:1.02‐1.36;P = 0.03) and higher Neuropsychiatric Inventory scores (OR:1.14, 95%CI:1.01‐1.28;P = 0.03) all independently increased the odds of being Diffuse, while higher Trails Making Test‐B (OR:0.99, 95%CI:0.98‐0.99;P = 0.02) and Block Design Test scores (OR:0.91, 95%CI:0.85‐0.99;P = 0.023) independently decreased the odds of being Diffuse. A “pathology” multivariate logistic regression fit to 233 cases with all neuropathological data revealed that widespread amyloid‐β pathology corresponding to Thal phases 3‐5 all significantly decreased the odds of diffuse pathology by 80‐90%, while hippocampal sclerosis increased it sixfold (OR:6.18, 95% CI:2.93‐13.03;P&lt;0.001).ConclusionsDiffuse AD‐TDP shows clinicopathological features that differ from Limbic AD‐TDP, which could have public health implications relating to treatment and research on AD and dementia.

Genetic heterogeneity of Alzheimer’s disease: Evidence for disease‐relevant and disease‐specific clustering

AbstractBackgroundAlzheimer’s disease (AD) demonstrates heterogeneity across domains of cognitive impairment, atrophy, and pathological accumulation. This has led to speculations that AD may comprise several disease subtypes. AD is under substantial genetic influence, thus searching for genetic clustering may provide insight towards the origins of this phenotypic variability.MethodGenotyping data from 2,739 AD cases and 5,478 age and sex‐matched controls from the UK Biobank were used as the discovery data. A principal components analysis (PCA) was applied to AD‐associated variants (p&lt;0.05 in the IGAPS2 GWAS of AD) to assess disease‐relevant structure. A novel biclustering algorithm was then applied to find disease‐specific genetic signatures of AD. This algorithm searches for subsets of subjects and variants that are present in cases, but importantly, not in controls. Pathway analysis was used to characterize the biological pathways implicated by disease‐relevant and specific clustering. Data from 476 AD cases and 591 controls from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) were used to test replication of clusters.ResultPCA revealed 3 distinct clusters. Each cluster contained a mix of cases and controls but these clusters only became apparent when restricting to AD‐associated variants, suggesting disease‐relevant structure. Examining clusters separately, we found 2 significant disease‐specific biclusters comprising sets of variants found more frequently in a subset of AD cases than in controls. When projecting ADNI data on UK Biobank principal components, there was almost perfect overlap of disease‐relevant clusters. Disease‐specific biclusters significantly replicated (p&lt;0.05) across a range of parameter choices.ConclusionThese findings demonstrate a hierarchy of heterogeneity for AD genetic risk. At the first level, the three disease‐relevant clusters may indicate that different pathways are more vulnerable for different groups of individuals, but additional risk factors or insults are required to substantially increase risk for AD. At the next level, individuals assigned to the biclusters may represent subtypes of AD with different genetic signatures that significantly increase risk for AD. Replication in ADNI demonstrates that this hierarchical structure is a generalizable aspect of AD genetic risk. More broadly, this study illustrates an approach that can be extended to investigate genetic heterogeneity of other complex diseases.

Novel quantitative method for characterization of hippocampal sclerosis and its association with other neuropathologies and cognitive deficits

AbstractBackgroundHippocampal sclerosis of aging (HS) is characterized by neuronal loss and astrogliosis in subiculum and/or CA1 subfield of hippocampus. Using a novel quantitative approach, we studied the prevalence and localization of HS pathology in a well‐characterized oldest‐old cohort and examined its association with other neuropathologic changes and cognitive impairment.MethodsWe studied 409 consecutive autopsied participants of The 90+ Study with longitudinal assessments. In those with HS by traditional method (presence/absence), we used digitized hematoxylin and eosin and luxol fast blue hippocampal slides for further quantitative analysis. Using QuPath, we measured the length of each hippocampal subfield partitioned into three subregions (Figure1). We then calculated the proportion affected by HS for each subregion. Both traditional (presence/absence) and quantitative (subfield‐specific proportions) measures were used to study the relationship between HS and other neuropathologic changes and cognitive outcomes using regression models adjusted for sex, age at death, and education with all neuropathologic changes as covariates.ResultsHS was present in 11% of participants and was always focal, mostly affecting CA1 (89%), followed by subiculum (27%). Overlapping CA1/subiculum pathology was seen in 16% (Figure2). Left‐sided HS was more frequent (75%) than right‐sided (18%). Bilateral cases were the least frequent (7%). HS presence (traditional measure) was only associated with Limbic‐predominant age‐related TDP‐43 encephalopathy (LATE) (OR = 3.45, p&lt;0.001). Quantitative measures revealed that HS proportion in subiculum and CA1 was associated with arteriolosclerosis (t36 = 4.11, p = 0.001) and LATE (t35 = 2.98, p = 0.005). HS proportion in subiculum alone was inversely associated with microvascular lesions (t41 = ‐3.16, p = 0.003) (Table1). HS proportion in subiculum and CA1 was associated with dementia at death and impairment of memory, language, calculation, and orientation. HS proportion in subiculum was additionally associated with impaired executive function. HS traditional measure was only associated with impaired orientation (Table1).ConclusionBased on our novel quantitative analysis, HS pathology was always focal, mostly unilateral, and associated with dementia and impairment in major cognitive domains. We found associations between HS and vascular pathologies that were not detected using traditional measure. The associations of HS with dementia and impaired memory, language, and calculation, identified with our quantitative method, were not detected using traditional measure.

Association of sarcopenia with cognitive impairment in older adults in the open population

AbstractBackgroundSarcopenia is a progressive and generalised skeletal muscle condition where there is a loss of muscle mass and function, while cognitive impairment is a clinical syndrome characterised by impairment in different cognitive and neuropsychological domains. Cognitive impairment has been studied as a risk factor for sarcopenia, however, it has not been established whether sarcopenia is a risk factor for cognitive impairment.MethodThis is a secondary analysis of 2,158 adults aged 65 and over assessed within the Dementia Research Group 10/66 protocols. In which grip strength, calf circumference and physical performance were measured to establish a diagnosis of sarcopenia. In addition, they were divided into groups depending on cognitive status.ResultOf all the older adults assessed, those with cognitive impairment or dementia had worse indicators in anthropometric measurements and in sarcopenia‐related measurements.ConclusionIn older Mexican adults, the presence of sarcopenia was not found to be associated with mild cognitive impairment, but was associated with the presence of dementia, even after controlling for other risk factors widely documented in the literature.

The evaluation of translated neuropsychological assessments tools for the early detection of mild cognitive impairment (MCI) in low‐ and middle‐income countries (LMICs)

AbstractBackgroundThe incidence of mild cognitive impairment (MCI), particularly in low and middle‐income countries (LMICs) has been noticeably on the rise. With the high cost of dementia care, the need for tools that aid with the early detection of MCI is becoming of high importance, especially in LMICs. As a part of screening for MCI, many tests have been proposed evaluating for impairments in cognitive, behavioral, and functional domains, which are important for ruling out and evaluating for any reversible causes. While useful, most of these tests were developed in the west, limited works exist reporting the appropriateness and experience of using such tests for patients from LMICs.MethodIn this work, we aim to evaluate the use of translated digital assessment for detecting MCI in an Arabic‐speaking population in Palestine. For this purpose, we developed a digital test covering three cognitive, behavioral, and functional domains, where MMSE and the Neuropsychiatric Inventory ‐ Questionnaire (NPI‐Q) together with two functional assessment questionnaires were translated to Modern Standard Arabic (MSA) and presented in a digital interface. Upon the development and translation of the digital tests, field testing was conducted to check for use experience and appropriate patient comprehension of the questions to match their intended use.ResultFollowing the implementation of the digital assessment tools, quantitative and qualitative data was collected summarizing the user experience, where numerous limitations were noted. Despite being asked in their native language, several patients expressed the need for more clarifying questions. While all patients were Arabic speakers, some patients required the use of simpler terminology that matches their local dialects. Other patients reported the lack of relevance of certain questions, regarding the activities of daily living in the functional assessments. Overall, the patient’s experience and comprehension of questions varied with their age and literacy level.ConclusionDespite the high prevalence of dementia in LMICs, there are limited available neuropsychological assessment tools that are fit for the local cultural and linguistic. The findings suggest the need for the development of culturally and linguistically appropriate assessments to ensure appropriate patient comprehension, and avoid misdiagnosis of patients.

TSH levels versus impairment of cognitive and affective domains in older adults: A secondary analysis of MHAS

AbstractBackgroundTSH levels are associated to symptoms such as bradypsychia, bradylalia, hypoprosexia, decreased learning ability, memory impairment and even depressive symptoms, affecting cognitive domains.MethodA secondary analysis of National Study of Health and Aging in Mexico (MHAS) from population interviewed in 2012 with TSH levels (1.948) regarding people with (1287) and without (661) congnitive impairment, in comparison to a follow‐up in 2018 (849 people) based on the same cognitive domains and TSH levels.ResultCognitive impairments were higher in women than men, specially around 60 years. The most affected impairment was no amnesic unidomain. People included have mostly normal thyroid function, but people with worst THS levels, commit more than one cognitive domain.ConclusionTSH levels control reduce the progression of cognitive impairment.

Association between oral health and cognitive frailty in community‐dwelling older adults

AbstractBackgroundCognitive frailty indicates the presence of both physical frailty and mild cognitive impairment (MCI) and has been associated with an increased risk of adverse health outcomes (e.g., mortality). Poor oral health has been related to cognitive impairment and physical frailty, respectively. However, the association between oral health and cognitive frailty remains unclear. This study aimed to explore the association between oral health and cognitive frailty in community‐dwelling older adults.MethodThis 10‐year cohort study (2011‐2021) is a part of an ongoing prospective cohort study. At baseline (2011‐2013), 605 non‐demented community‐dwelling older adults (aged 65+) with four biennial follow‐ups. Cognitive frailty was defined as the coexistence of MCI and physical frailty. Extended definitions of cognitive frailty were also assessed and defined as the coexistence of impaired cognitive domains and physical frailty. Oral health variables included tooth defects, dentition, and periodontal status. The generalized linear mixed model was used to explore the longitudinal association between oral health and cognitive frailty, adjusting for age, sex, lifestyle, comorbidity, and so on.ResultThe mean age of the study participants was 72.7 at baseline, and 53.4% were female. We found that tooth defect was associated with worsening of impaired memory‐frailty [adjusted odds ratio (aOR) = 1.13; 95% confidence interval (CI) = 1.03‐1.24] and impaired verbal fluency‐frailty (aOR = 1.07; 95% CI = 1.00‐1.11) over time; Dentition was associated with worsening of impaired executive function‐frailty (aOR = 1.10; 95% CI = 1.02‐1.18) over time; Periodontal status was associated with worsening of impaired memory‐frailty (aOR = 1.07; 95% CI = 1.02‐1.13) and verbal fluency‐frailty (aOR = 1.05; 95% CI = 1.00‐1.11) over time. No significant associations were found for traditional cognitive frailty and impaired attention‐frailty.ConclusionCognitive frailty is associated with oral health after adjusting for covariates. Inspection of oral health is helpful to predict the risk of cognitive impairment at an early stage. Further research on this topic is warranted to validate our findings.

Prevalence of Cognitive Domain Impairments in Mild Cognitive Impairment Subtypes in the NACC Database

AbstractBackgroundMild cognitive impairment (MCI) reflects cognitive deficits without significant functional decline in activities of daily living. MCI subtypes correspond to phenotypic cognitive impairment patterns in memory, attention, language, executive, and visuospatial compared to age‐adjusted norms: Amnestic single domain (ASD) or multi‐domain (AMD), Nonamnestic single domain (NASD), or Nonamnestic multi‐domain (NAMD. In this study, we explore frequencies of domain impairment by MCI subtype, and frequency of each combination of (memory ±) all combinations of Language, Attention, Executive and Visuospatial impairment in the NACC database. This is of practical importance for both localization of amyloid or tau deposition as well as relative localization of areas of deficit.MethodUsing the National Alzheimer’s Coordinating Center (NACC) database (grant U24 AG072122), we selected all initial Uniform Data Set (UDS) assessments diagnosed as MCI with sub‐typing. The NACC data was collected from 37 participating Alzheimer’s disease Research Centers. 9852 individuals with MCI on baseline UDS visits were analyzed: 45.4% AMD, 33.7% ASD, 12.6% NASD, 8.2% NAMD.ResultFigure one shows the distribution overall of domain specific impairment by MCI subtype. Except for ASD, Executive function was the most common domain affected, and visuospatial was the least common. NAMD had higher percentages affected for all domains compared to AMD. In Figure 2, all combinations of language, executive, attention and visuospatial are compared. The most frequent combination was Language‐Executive, and the least common combination was Language‐Attention‐Visuospatial. The mean absolute percentage difference between AMD and NAMD was 2.2%. The Spearman’s rho of AMD vs. NAMD was 0.845.ConclusionWithin an MCI subtype, there is substantial variability in the frequency of individual domains. However, comparison of AMD and NAMD shows striking uniformity in frequency of combinations of individual domains with very correlation. The latter findings suggests that Amnestic and Nonamnestic multidomain subtypes may be closely related in pathophysiology but show greater heterogeneity within a MCI subtype.

Clinical Manifestations.

The incidence and prevalence of dementia continue to increase exponentially as people age. Finding a pre-clinical marker to detect dementia early is paramount in clinical practice. There are few prospective studies evaluating handgrip strength, handgrip strength asymmetry, and their combination on cognitive impairment. This study aimed to investigate the association of handgrip strength and handgrip strength asymmetry with future global and specific cognitive domain impairment. This is a seven-year prospective cohort study (Fig 1). We used data from the ongoing Taiwan Initiative of Geriatric Epidemiological Research (TIGER), wave 3 (2015-2017) to wave 5 (2019-2022), with wave 3 as the baseline (n = 446). Low handgrip strength was defined as the lowest tertile of sex-specific handgrip strength. Handgrip strength asymmetry was defined as a handgrip strength ratio <0.85 or >1.15 (i.e., a 15% difference). The cognitive assessment included global and specific cognitive domains. Generalized linear mixed models were used to assess the association of handgrip strength asymmetry and cognitive performance adjusted for age, years of education, cigarette smoking, alcohol drinking, hypertension, diabetes, hyperlipidemia, and physical activity. The mean age of participants was 75.7 years, and 55% were female. Participants with handgrip strength asymmetry were mostly female, never smokers, and more likely to have lower handgrip strength. Handgrip strength asymmetry was associated with poor global cognition [ = -2.14, 95% confidence interval (CI): -3.60, -0.68] and digit span-forward ( = -0.69, 95% CI: -1.25 to -0.14) over time in men. Low handgrip strength was associated with cognitive impairment (global cognition: = -1.13, 95% CI: -2.07 to -0.19; immediate free recall: = -0.48, 95%CI: -0.87 to -0.09; delayed free recall: = -0.45, 95% CI: -0.85 to -0.08); Trail Making Test- A: = -0.43, 95% CI: -0.75 to -0.12), and digit span-forward ( = -0.67 to 95% CI: -1.02 to -0.31) over time in men. Concomitant weakness and handgrip strength asymmetry had greater impairment in cognitive function in men. In this community-dwelling older population, those with low handgrip strength and handgrip strength asymmetry had an increased risk of cognitive impairment. This relationship seems more prominent in men than women.

Birth, cognitive and behavioral effects of intrauterine cannabis exposure in infants and children: A systematic review and meta-analysis.

Δ9-tetrahydrocannabinol (THC), the principal psychoactive component of cannabis, has been implicated in affecting fetal neurodevelopment by readily crossing the placenta. However, little is known regarding the long-term effects of intrauterine cannabis exposure. This systematic review and meta-analysis synthesized prospective and cross-sectional human studies to measure the effects of intrauterine cannabis exposure on birth, behavioral, psychological and cognitive outcomes in infancy until early childhood. Reporting according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement, cross-sectional and prospective studies published from database inception until June 2023, investigating developmental outcomes of infants, toddlers and young children with intrauterine cannabis exposure were considered. All articles were obtained from PubMed or PsycINFO databases. The literature search resulted in 932 studies, in which 57 articles met eligibility criteria. The meta-analysis revealed that intrauterine cannabis exposure increases the risk of preterm delivery [odds ratio (OR) = 1.68, 95% confidence interval (CI) = 1.05-2.71, P = 0.03], low birth weight (OR = 2.60, CI = 1.71-3.94, P < 0.001) and requirement for neonatal intensive care unit (NICU) admission (OR = 2.51, CI = 1.46-4.31; P < 0.001). Our qualitative synthesis suggests that intrauterine cannabis exposure may be associated with poorer attention and externalizing problems in infancy and early childhood. We found no evidence for impairments in other cognitive domains or internalizing behaviors. Prenatal cannabis use appears to be associated with lower birth weight, preterm birth and neonatal intensive care unit admission in newborns, but there is little evidence that prenatal cannabis exposure adversely impacts behavioral or cognitive outcomes in early childhood, with the exception of attention and externalizing problems.

A new approach for cognitive impairment pattern in chronic kidney disease.

Chronic kidney disease (CKD) is associated with an elevated risk of neurocognitive disorders (NCDs). It remains unclear whether CKD-related NCDs have a specific cognitive pattern or are earlier-onset phenotypes of the main NCDs (vascular NCDs and Alzheimer's disease). We used the Mini Mental State Examination score (MMSE) to assess cognitive patterns in 3003 CKD patients (stage 3-4) followed up over 5 years in the Chronic Kidney Disease-Renal Epidemiology and Information Network (CKD-REIN) cohort. After normalizing MMSE scores to a 0-to-100 scale, the associations between the baseline estimated glomerular filtration rate (eGFR, using the Chronic Kidney Disease Epidemiology Collaboration creatinine formula) and changes in each MMSE domain score were assessed in linear mixed models. Patients (age: 67±13years old; males: 65%, mean eGFR: 33± 12mL/min/1.73m2) had a good baseline cognitive functions: the mean MMSE score was 26.9/30±2.9. After adjustment for age, sex, educational level, depression (past or present), cardiovascular risk factors and cerebrovascular disease, a lower baseline eGFR (per 10mL/min/1.73m2) was associated with a 0.53-point decrement [P<.001; 95% confidence interval (CI) (-0.98, -0.08)] for orientation, a 1.04-point decrement [P=.03; 95% CI (-1.96, -0.13)] for attention and calculation, a 0.78-point decrement [P=.003; 95% CI (-1.30, -0.27)] for language, and a 0.94-point decrement [P=.02; 95% CI (-1.75, -0.13)] for praxis. Baseline eGFR was not, however, associated with significant changes over time in MMSE domain scores. A lower eGFR in CKD patients was associated with early impairments in certain cognitive domains: praxis, language and attention domains before an obvious cognitive decline. Early detection of NCD in CKD patients must be performed before clinically cognitive decline using preferably tests assessing executive, attentional functions and language, rather than memory tests. This early cognitive screening could lead to a better management of cognitive impairment and their consequences on CKD management.

Cognitive phenotypes predict response to restorative cognitive rehabilitation in multiple sclerosis

Background: Cognitive phenotyping may be useful for predicting rehabilitation response in multiple sclerosis. Objective: To evaluate the association between cognitive phenotype(s) and response to restorative cognitive rehabilitation (RRCR). Methods: In a post hoc retrospective analysis of the RRCR study including 51 multiple sclerosis patients, we evaluated both impairment within specific cognitive domains as well as overall global impairment severity to investigate their relationship to improvement following rehabilitation. Results: Greater improvement in executive function was predicted by impairment within this domain as well as by having fewer impaired cognitive domains overall. Similar results were observed for visuospatial memory. Conclusions: Patients most likely to benefit from restorative cognitive rehabilitation may exhibit impairment within the domain of interest yet lower cognitive burden overall.