Domain-specific Cognitive Impairment Research Articles

Post-stroke fatigue severity is associated with executive dysfunction in chronic stroke

ABSTRACT Following stroke, fatigue is highly prevalent and managing fatigue is consistently rated a key unmet need by stroke survivors and professionals. Domain-specific cognitive impairments have been associated with greater fatigue severity in earlier stages of stroke recovery, but it is unclear whether these associations hold in chronic (>2 years) stroke. The present cross-sectional observational study evaluates the relationship between domain-specific cognitive functioning and the severity of self-reported fatigue among chronic stroke survivors. Participants (N = 105; mean age = 72.92, 41.90% female; mean years post-stroke = 4.57) were assessed in domains of attention (Hearts Cancellation test), language (Boston Naming Test), episodic memory (Logical Memory Test), working memory (Digit Span Backwards task), and executive functioning (set-shifting: Trail Making Test, Part B), as part of the OX-CHRONIC study, a longitudinal stroke cohort. Fatigue was assessed using the Fatigue Severity Scale. In a multiple linear regression analysis inclusive of above cognitive domains, only poorer executive functioning was associated with increased fatigue severity. This provides insight into the cognitive impairment profile of post-stroke fatigue long-term after stroke, with executive functioning deficits as the key hallmark.

Multivariate and network lesion mapping reveals distinct architectures of domain-specific post-stroke cognitive impairments

BackgroundThe purpose of this study was to identify patterns of structural disconnection and multivariate lesion-behaviour relationships associated with post-stroke deficits across six commonly impacted cognitive domains: executive function, language, memory, numerical processing, praxis, and visuospatial attention. MethodsStroke survivors (n = 593) completed a brief domain-specific cognitive assessment (the Oxford Cognitive Screen (OCS)) during acute hospitalisation. Network-level and multivariate (sparce canonical correlation) lesion mapping analyses were conducted to identify focal neural correlates and distributed patterns of structural disconnection associated with impairment on each of the 16 OCS measures. ResultsNetwork-level and multivariate lesion mapping analyses identified significant correlates for 12/16 and 10/16 OCS measures, respectively which were largely consistent with correlates reported in past work. Language impairments were reliably localised to network- and voxel-level correlates centred in left fronto-temporal regions. Memory impairments were associated with disconnection in a large network of left hemisphere regions. Number processing deficits were associated with damage to voxels centred in the left insular/opercular cortex, as well as disconnection within the surrounding white matter tracts. Within the domain of attention, different subtypes of visuospatial neglect were linked to distinct but partially overlapping patterns of disconnection and voxel-level damage. Praxis impairment was not linked to any voxel-level regions but was significantly associated with disconnection within the left hemisphere dorsal attention network. ConclusionThese results highlight the utility of routine, domain-specific cognitive assessment and imaging data for theoretically-driven lesion mapping analyses, while providing novel insight into the complex anatomical correlates of common and debilitating post-stroke cognitive impairments.

Chronic pain is specifically associated with updating working memory: a longitudinal twin study.

Worse executive function (EF) is associated with chronic pain and could mechanistically contribute to pain chronification. It is unclear whether there is overall impairment in EFs or whether there are impairments in specific cognitive domains. Furthermore, the possible genetic risk underlying these associations has not been tested. Participants were from the Colorado Longitudinal Twin study; 786 same-sex twins completed a battery of EF tasks at ages 23 and/or 28 and 634 of these twins self-reported chronic pain at mean age = 28.1; prevalence = 27.76% using the Brief Pain History Questionnaire. The EF tasks were used to define a Common EF factor and 2 factors specific to updating working memory and shifting mental set. We estimated the phenotypic and genetic associations of stable EF variance across ages 23 and 28, as well as EF variance unique to age 28, with pain. With respect to stable EF variance, pain phenotypically correlated with the Updating-specific factor (r = -0.21, P = 0.008) but did not significantly correlate with the Common EF factor (r = -0.06, P = 0.350) nor with the Shifting-specific factor (r = -0.03, P = 0.709). There were no significant phenotypic correlations between pain and EF variance unique to age 28. A twin model indicated that pain and Updating-specific variance share genetic risk (rA = -0.46, P = 0.005) but not environmental risk (rE = 0.05, P = 0.844). Updating working memory shares a phenotypic and genetic relationship with pain in young adults. Impairments in gating or monitoring pain signals may play a mechanistic role in pain development.

Association between possible sarcopenia and domain-specific cognitive impairment in middle-aged and older adults: Insights from the Gan-Dau Healthy Longevity Plan

BackgroundGiven the established association between sarcopenia and cognitive impairment was mainly in the older and oldest-old population or people with relatively limited education, this study extends the investigation to community-dwelling middle-to-old age adults in urban communities, emphasizing the need for preventive intervention for muscle health and healthy longevity. MethodsData of 712 participants from the Gan-Dau Healthy Longevity Plan were retrieved for analysis, and all participants were stratified by age (50–64, 65–74 and 75+ years old). Possible sarcopenia was defined by 2019 consensus report of the Asian Working Group for Sarcopenia (AWGS). This study used four neuropsychological tests for analysis, i.e., Mini-Mental Status Examination (MMSE), California Verbal Learning Test II (CVLT-SF), Digital Symbol Substitution Test (DSST) and Verbal fluency (VF) for global and domain-specific cognitive function. Multivariate generalized linear models (GLMs) were employed to investigate the associations between possible sarcopenia and cognitive function in each age-specific groups. ResultsThe prevalence of possible sarcopenia increased with age, with 31.8 %, 37.7 %, and 55.6 % in participants aged 5064, 65–74 and, 75+ years, respectively. On the other hand, cognitive performance declined with age. In particular, among participants aged 75+ years with possible sarcopenia, their cognitive performance were poorer than robust counterparts, including MMSE (26.6 [3.4] vs. 27.4 [2.6]), CVTL-SF (total score: 21.5 [5.4] vs. 23.8 [5.5]; 30-second delayed recall: 6.0 [1.7] vs. 6.5 [1.6]), DSST (32.8 [14.3] vs. 41.3 [18.7]), and VF (12.8 [5.1] vs. 14.8 [4.9]). Multivariate generalized linear model indicated that possible sarcopenia was associated with lower MMSE (β: −0.70, p = 0.014) and lower DSST (β: −7.00, p = 0.010) in those aged 50–64 years. Moreover, possible sarcopenia was associated with lower CVLT-SF (total score β:-1.90, p = 0.028), lower DSST (β: −6.45, p < 0.001), and lower VF (β: −1.64, p=0.026) in 75+ years group. ConclusionsAn association exists between possible sarcopenia and cognitive impairment, encompassing global cognition, delayed memory, verbal fluency, and executive function, among community-dwelling adults of mid-to-old age. Future research is warranted to explore the temporal alterations in this association and the potential effects of interventions aimed at fostering healthy longevity.

Cohort profile: the Taiwan Initiative for Geriatric Epidemiological Research - a prospective cohort study on cognition.

The Taiwan Initiative for Geriatric Epidemiological Research (TIGER) was founded in 2011 to elucidate the interrelationships among various predictors of global and domain-specific cognitive impairment, with the aim of identifying older adults with an increased risk of dementia in the preclinical phase. TIGER, a population-based prospective cohort, recruited 605 and 629 (total of 1,234) older adults (aged 65 and above) at baseline (2011-2013 and 2019-2022) of phase I and II, respectively. Participants have undergone structured questionnaires, global and domain-specific cognitive assessments, physical exams, and biological specimen collections at baseline and biennial follow-ups to date. By 2022, TIGER I has included 4 biennial follow-ups, with the participants comprising 53.9% female and having a mean age of 73.2 years at baseline. After an 8-year follow-up, the annual attrition rate was 6.1%, reflecting a combination of 9.9% of participants who passed away and 36.2% who dropped out. TIGER has published novel and multidisciplinary research on cognitive-related outcomes in older adults, including environmental exposures (indoor and ambient air pollution), multimorbidity, sarcopenia, frailty, biomarkers (brain and retinal images, renal and inflammatory markers), and diet. TIGER's meticulous design, multidisciplinary data, and novel findings elucidate the complex etiology of cognitive impairment and frailty, offering valuable insights into factors that can be used to predict and prevent dementia in the preclinical phase.

The effects of sensorial and mobility frailty on the overall and domain-specific cognition performance of Chinese community-dwelling older adults.

This study aimed to investigate the different impacts of sensorial and mobility frailty on overall and domain-specific cognitive function. Further, the independent associations between other intricate capacity (IC) dimensions, including vitality and psychological dimensions, and overall and domain-specific cognitive function were investigated. A total of 429 participants (mean age, 72.91 ± 7.014 years; 57.30% female) underwent IC capacity assessment. Other covariates, such as demographics, health-related variables were also assessed. Overall or domain-specific cognitive impairment was used as a dependent variable in logistic regression analyses adjusted for demographic, health-related, and psychosocial confounders. After adjustment for demographic, health-related, and psychosocial confounders, individuals with sensorial frailty (odds ratio [OR] = 0.435; 95% confidence interval [CI] = 0.236-0.801; P = .008) had a significantly lower risk of mild cognitive impairment (MCI), marginally low delayed memory impairment (OR = 0.601, 95% CI = 0.347-1.040; P = .069), and language impairment (OR = 0.534, 95% CI = 0.305-0.936; OR = 0.318, P = .029; OR = 0.318,95% CI = 0.173-0.586; P < .001) by Boston naming and animal fluency tests than did those with both sensorial and mobility frailty or mobility frailty only. Depressive symptoms had a significant negative influence on executive function. Cardiovascular disease and non-skin malignancy were independent determinants of MCI, and diabetes mellitus was independently associated with processing speed, attention, and executive function. Sensorial and mobility frailty were independent risk factors for cognitive impairment. Mobility frailty had a greater negative influence on the overall cognitive function and memory and language function than did sensorial frailty. The reserve decline in the psychological dimension of IC and chronic diseases also had a significant adverse influence on overall and domain-specific cognition function.

Domain-specific cognitive impairments, mood and quality of life 6 months after stroke

Purpose To identify which acute and 6-month domain-specific cognitive impairments impact mood, participation, and stroke-related quality of life 6 months post-stroke. Materials and methods A prospective cohort of 430 stroke survivors completed the Oxford Cognitive Screen (OCS) acutely and 6 months post-stroke. Participants completed the Stroke Impact Scale (SIS) and Hospital Depression and Anxiety Scale (HADS) at 6 months. Multivariable regression analyses assessed whether severity of, and domain-specific, cognitive impairment acutely and at 6 months was associated with composite 6-month SIS scores, each SIS subscale, and HADS scores. Results Increased severity of acute and 6-month cognitive impairment was associated with lower 6-month SIS composite scores independent of age, sex, education years, and stroke severity (both p < 0.001). Domain-specific impairments in memory (p < 0.001) and attention (p = 0.002) acutely, and language (p < 0.001), memory (p = 0.001) and number processing (p = 0.006) at 6 months showed the strongest associations with worse SIS composite scores. Severity of acute and 6-month cognitive impairment was associated with poorer functioning in each SIS subscale, and greater levels of depression (acute p = 0.021, 6-months p < 0.001), but not anxiety (p = 0.174, p = 0.129). Conclusions Both acute and 6-month domain-specific cognitive impairments, particularly in memory, were found to negatively impact overall functional and mood outcomes 6 months post-stroke.

Predictors of post stroke cognitive impairment: VITATOPS cognition substudy

IntroductionPost stroke cognitive impairment (PSCI) is a common complication of ischemic stroke. PSCI can involve different depending on clinical and stroke related characteristics. The aim of this study is to determine the factors associated with impairments in specific cognitive domains. MethodsThe Vitamins to Prevent Stroke (VITATOPS) trial is a large, multinational randomised controlled trial. In this substudy, consecutive patients admitted for ischaemic stroke or transient ischaemic attack (TIA) at a tertiary hospital in Singapore were included. PSCI was defined as impairment of any of the six cognitive subgroups – visuoconstruction, attention, verbal memory, language, visual memory and visuomotor function – that were assessed annually for up to five years. Univariate and multivariate Cox proportional hazard models were used to determine factors associated with impairments in each of these cognitive domains. ResultsA total of 736 patients were included in this study, of which 173 (23.5 %) developed cognitive impairment. Out of the six cognitive domains, the greatest proportion of patients had an impairment in visuoconstruction (26.4 %) followed by attention (19.8 %), verbal memory (18.3 %), language (17.5 %), visual memory (17.3 %) and visuomotor function (14.8 %). Patients with posterior circulation cerebral infarction (POCI) as the index stroke subtype had higher rates of cognitive impairment. Further subgroup analyses show that Indian race and advanced age were predictive of language impairment, whilst fewer years of education and POCI were predictive of verbal memory impairment. POCI was predictive of visual memory impairment, and advanced age and POCI were predictive of visuomotor function impairment. ConclusionWe identified visuoconstruction and attention domains to be the most affected in our Asian cohort of PSCI. Advanced age, lower levels of education, posterior circulation strokes and concomitant comorbidities such as peripheral artery disease are independent predictors of PSCI.

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.

Infection, Inflammation, and Poststroke Cognitive Impairment.

Infection and inflammation are dementia risk factors in population-based cohorts; however, studies in stroke are scarce. We determined the prevalence of infection after stroke and routinely measured inflammatory biomarkers during hospitalization and their associations with acute and 6-month cognitive impairment. A prospective stroke cohort completed the Oxford Cognitive Screen at ≤2 weeks and 6 months after stroke. Infection, inflammatory markers (C-reactive protein, white cell count, and neutrophil/lymphocyte ratio), and systemic inflammatory response syndrome were ascertained throughout admission with electronic patient records supplemented by hand searches. Associations with acute and 6-month global and domain-specific cognitive impairment were analyzed using multivariable regression, adjusting for demographic/vascular factors and stroke severity. Among 255 patients (mean age, 73.9 [SD, 12.6] years; 46.3% women; mean education, 12.6 [SD, 3.7] years; median National Institutes of Health Stroke Scale score 5 [range, minimum-maximum, 0-30]), infection was present in 90 patients (35.3%) at mean 4.4 (SD, 6.9) days after stroke, consisting predominantly of pneumonia (47/90; 52%) and urinary tract infection (39/90; 43%). Admission white cell count was elevated in 25.1% (n=64; mean, 9.5×109/L [SD, 3.2×109/L]), C-reactive protein in 41.2% (n=105; mean, 27.5 [SD, 50.9 mg/L]), neutrophil/lymphocyte ratio in 55.7% (n=97; mean, 5.5 [SD, 4.5]), and systemic inflammatory response syndrome in 26.6% (n=53 [45.2%] positive during hospitalization). Infection was associated with acute and 6-month poststroke cognitive impairment (P<0.05adj) with stronger associations acutely for severe infection (infection+systemic inflammatory response syndrome; P=0.03adj). Acute language, executive function and attention domain impairments, and 6-month number processing impairment were associated with infection (P<0.05adj). No significant relationships were found for any biomarker and cognitive impairment. Infection and elevations in routinely measured inflammatory biomarkers are common following stroke; however, only infection is associated with poststroke cognitive impairment, suggesting that increases in these biomarkers may be nonspecific. Infection may present a tractable target for reducing poststroke cognitive impairment.

Domain-specific cognitive impairment in multiple sclerosis: A systematic review and meta-analysis.

Methods of cognitive measurements in multiple sclerosis (MS) are not standardized. We aimed to identify the prevalence of cognitive domain-specific impairment (DSI) in MS by using subtests of the Brief Repeatable Battery of Neuropsychological Tests (BRB-N) with analyzing different cutoff values. The systematic review and meta-analysis were registered on PROSPERO (ID: CRD42021287004). The systematic literature search was performed via PubMed, Embase, and CENTRAL on 24 October 2021. Inclusion criteria were adults of different MS subtypes (CIS, RRMS, PPMS, and SPMS) with the condition of distinct DSI measured by BRB-N. Pediatric MS, computerized versions of BRB-N, and patients receiving steroids were excluded. Primary outcome was pooled prevalence rates of impaired patients within each cutoff and MS subtype, with 95% confidence interval, I-squared statistics for heterogeneity, and chi-squared test for subgroup differences. Risk of bias was assessed using the "JBI Quality Assessment Tool for Prevalence Studies." In 48 eligible observational studies (n = 3431 patients), the three most prevalent thresholds were the 2.0 SD and 1.5 SD below the mean of normative values, and the score below the fifth percentile of the normative values. A progressively increasing worsening of the overall DSI was observed from CIS, moving toward RRMS, PPMS, and SPMS. Cognitive impairment is observed in all MS phenotypes, with varying degrees. Due to several potential influencing factors, our comprehensive literature review has not revealed consistent findings, and we, therefore, recommend considering a more sophisticated, "individual referencing" approach, acknowledging the diverse clinical and sociodemographic characteristics among populations and disparities in cognitive testing.

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.

Domain-specific cognitive impairment 6 months after stroke: The value of early cognitive screening.

Cognitive screening following stroke is widely recommended, yet few studies have considered the prognostic value of acute domain-specific function for longer-term cognitive outcome. Identifying which post-stroke cognitive impairments more commonly occur, recover, and persist, and which impairments hold prognostic value, could inform care planning, and resource allocation. This study aimed to determine the prevalence of domain-specific impairment acutely and at 6 months, assess the proportion of change in cognitive performance, and examine the prognostic value of acute domain-specific cognitive screening. A prospective stroke cohort completed the Oxford Cognitive Screen acutely (⩽2 weeks) and 6 months post-stroke. We determined the prevalence of acute and 6-month domain-specific impairment and proportion of change in performance from acute to 6 months. Hierarchical multivariable regression was used to predict global and domain-specific cognitive impairment at 6 months adjusted for demographic/vascular factors, stroke severity, and lesion volume. A total of 430 stroke survivors (mean/SD age 73.9/12.5 years, 46.5% female, median/interquartile range (IQR) National Institute of Health Stroke Scale (NIHSS) 5/2-10) completed 6-month follow-up. Acutely, domain-specific impairments were highly prevalent ranging from 26.7% (n = 112) in praxis to 46.8% (n = 183) in attention. At 6 months, the proportion of domain-specific recovery was highest in praxis (n = 73, 71%) and lowest in language (n = 89, 46%) and memory (n = 82, 48%). Severity of 6-month cognitive impairment was best predicted by the addition of acute cognitive impairment (adj R2 = 0.298, p < 0.0001) over demographic and clinical factors alone (adj R2 = 0.105, p < 0.0001). Acute cognitive function was the strongest predictor of 6-month cognitive performance (p < 0.0001). Acute domain-specific impairments in memory (p < 0.0001), language (p < 0.0001), and praxis (p < 0.0001) significantly predicted overall severity of cognitive impairment at 6 months. Post-stroke cognitive impairment is highly prevalent across all domains acutely, while impairments in language, memory, and attention predominate at 6 months. Early domain-specific screening can provide valuable prognostic information for longer-term cognitive outcomes.

Association of Neuroimaging Markers on Clinical CT Scans With Domain-Specific Cognitive Impairment in the Early and Later Post-Stroke Stages.

Post-stroke cognitive impairment (PSCI) is associated with neuroimaging markers, including cortical atrophy and white matter lesions (WMLs), on clinically acquired CT neuroimaging. To investigate the association between cortical atrophy/WMLs and PSCI in specific cognitive domains in the acute/subacute and chronic stages after stroke, in order to provide clarity on the relationship between these neuroimaging markers and the temporal evolution of PSCI. We visually assessed cortical atrophy using the Global Cortical Atrophy (GCA) scale and WMLs using the Fazekas scale. Oxford Cognitive Screen (OCS) or Birmingham Cognitive Screen (BCoS) assessed PSCI at two timepoints (acute/subacute and chronic) in six domains (language, memory, number processing, executive function, attention, praxis). We binarised domain-specific performance as impaired/unimpaired using normative cut-offs. Multivariable linear and logistic regression analyses evaluated associations between GCA/Fazekas scores with acute/subacute/chronic global and domain-specific PSCI, and ANCOVAs examined whether these scores were significantly different in patients with recovered versus persistent PSCI. Age, sex, education, NIHSS, lesion volume, and recurrent stroke were covariates in these analyses. Among 411 stroke patients (Mdn/IQR age= 76.16/16.64; 193 female; 346 ischaemic stroke; 107 recurrent stroke), GCA and Fazekas scores were not associated with global cognitive impairment in the acute/subacute stage after stroke, but GCA score was associated with chronic global PSCI (B = 0.01, p < .001, 95% CI [0.00 0.01]). In domain-specific analyses, GCA score was associated with chronic impairment in the memory (B = 0.06, p < .001, 95% CI [0.03 0.10]) and attention (B = 0.05, p = .003, 95% CI [0.02 0.09]) domains, and patients with persistent PSCI these domains showed significantly higher GCA scores than patients who had recovered (Memory: F(1,157) = 6.63, p = .01, η 2 G = .04; Attention: F(1,268) = 10.66, p = .001, η 2 G = .04). The present study highlights the potential impact of cortical atrophy on the cognitive recovery process after stroke and demonstrates the prognostic utility of CT neuroimaging for post-stroke cognitive outcomes. Clinical neuroimaging could help identify patients at long-term risk of PSCI during acute hospitalisation.

Cardiovascular Disease Risk Burden, Cognitive Impairments and Incident Dementia among Community-Dwelling Middle-Aged and Older Adults: An 8-Year Longitudinal Follow-up Study.

To evaluate the associations between cardiovascular disease (CVD) risk burden (estimated by the World Health Organization (WHO) algorithm) and cognitive impairments (e.g., incident dementia, global and domain-specific impairments) among CVD-, dementia- and disability-free, community-dwelling middle-aged and older adults during an 8-year follow-up. A community-based longitudinal cohort study. Yuanshan township in Yi-Lan County, Taiwan. A total of 889 community-dwelling residents aged 50 years or older. Age, sex, educational level, employment status, alcohol status, body mass index, physical activity, gait speed, depressive symptoms, WHO region-specific CVD risk scores (10-year CV risk, low: <10% vs. moderate-to-high: ≥ 10%), Chinese version of the Mini-Mental State Examination (MMSE), verbal memory by the delay-free recall in the Chinese Version Verbal Learning Test (CVVLT), language function by the Boston Naming Test and the category (animal) Verbal Fluency Test, visuospatial function by the Taylor Complex Figure Test, executive function by the digit backward and the Clock Drawing Test. Compared to those with low CVD risk, middle-aged and older adults with moderate-to-high CVD risk were at greater risk for cognitive impairments with respect to the MMSE (adjusted odds ratio (aOR) 1.60 [95% confidence interval (CI) 1.19-2.15], P=0.002), verbal memory (aOR 1.97 [1.43-2.70], P< 0.001) and language (aOR 1.99 [1.46-2.70], P< 0.001), as well as incident dementia (aOR 2.40 [1.33-4.33], P=0.004). After adjusting for all covariates, CVD risk was not associated with other domains of cognitive impairment. Among healthy, community-dwelling, middle-aged and older adults, those with moderate-to-high cardiovascular risk burden were significantly associated with incident dementia and global and domain-specific cognitive impairments (verbal memory and language), which suggests the existence of a relationship between early cognitive deficits and CVD risk burden. Further studies are needed to elucidate the pathophysiological mechanism of the link between CVD risk burden and cognitive impairment.

Domain-Specific Cognitive Impairment Reflects Prefrontal Dysfunction in Aged Common Marmosets.

Age-related cognitive impairment is not expressed uniformly across cognitive domains. Cognitive functions that rely on brain areas that undergo substantial neuroanatomical changes with age often show age-related impairment, whereas those that rely on brain areas with minimal age-related change typically do not. The common marmoset has grown in popularity as a model for neuroscience research, but robust cognitive phenotyping, particularly as a function of age and across multiple cognitive domains, is lacking. This presents a major limitation for the development and evaluation of the marmoset as a model of cognitive aging and leaves open the question of whether they exhibit age-related cognitive impairment that is restricted to some cognitive domains, as in humans. In this study, we characterized stimulus-reward association learning and cognitive flexibility in young adults to geriatric marmosets using a Simple Discrimination task and a Serial Reversal task, respectively. We found that aged marmosets show transient impairment in learning-to-learn but have conserved ability to form stimulus-reward associations. Furthermore, aged marmosets have impaired cognitive flexibility driven by susceptibility to proactive interference. As these impairments are in domains critically dependent on the prefrontal cortex, our findings support prefrontal cortical dysfunction as a prominent feature of neurocognitive aging. This work positions the marmoset as a key model for understanding the neural underpinnings of cognitive aging.

Neurocognitive effects of androgen deprivation therapy and new hormonal agents in a sample of patients with metastatic prostate cancer

IntroductionAlthough the growing treatment landscape for metastatic prostate cancer (mPC) has revealed new opportunities, it has also provided challenges, such as undesirable side effects. The aim of the present study was to provide further data on domain-specific cognitive impairments in mPC patients with androgen deprivation therapy (ADT) and new hormonal agents.MethodsFifty-eight patients (71 ± 8 years) with mPC were investigated using a cross-sectional design. All patients had received some form of ADT (93% had received luteinizing hormone-releasing hormone (LHRH) analogs/antagonists), 66% had received chemotherapy, and 84% had received anti-resorptive therapy. We evaluated learning and memory, processing speed, and executive functions, as recommended by the International Cognition and Cancer Task Force, to determine neurocognitive deficits.ResultsPatients treated with ADT scored significantly lower on all neurocognitive tests and showed significantly more neurocognitive deficits (38–62%) than age-adjusted reference samples (16%, p < 0.05). Cognitive deficits were mild in most cases and predominantly affected visuomotor processing speed (48%). Moderate and severe deficits were found in 11% and 5% of patients, respectively, with word fluency as the predominant deficit (23%). No associations were found between the type or duration of treatment and the severity of cognitive deficits.ConclusionsTreatment of mPC with ADT is correlated with neurocognitive deficits in several cognitive domains. Language skills and processing speed were most frequently impaired. However, a consistent pattern of cognitive impairment was not identified. Neurocognitive deficits should be considered in phase III and IV trials.Trial registrationThe study was registered in the German Clinical Trials Registry (DRKS00017727).

A genome-wide search for pleiotropy in more than 100,000 harmonized longitudinal cognitive domain scores

BackgroundMore than 75 common variant loci account for only a portion of the heritability for Alzheimer’s disease (AD). A more complete understanding of the genetic basis of AD can be deduced by exploring associations with AD-related endophenotypes.MethodsWe conducted genome-wide scans for cognitive domain performance using harmonized and co-calibrated scores derived by confirmatory factor analyses for executive function, language, and memory. We analyzed 103,796 longitudinal observations from 23,066 members of community-based (FHS, ACT, and ROSMAP) and clinic-based (ADRCs and ADNI) cohorts using generalized linear mixed models including terms for SNP, age, SNP × age interaction, sex, education, and five ancestry principal components. Significance was determined based on a joint test of the SNP’s main effect and interaction with age. Results across datasets were combined using inverse-variance meta-analysis. Genome-wide tests of pleiotropy for each domain pair as the outcome were performed using PLACO software.ResultsIndividual domain and pleiotropy analyses revealed genome-wide significant (GWS) associations with five established loci for AD and AD-related disorders (BIN1, CR1, GRN, MS4A6A, and APOE) and eight novel loci. ULK2 was associated with executive function in the community-based cohorts (rs157405, P = 2.19 × 10–9). GWS associations for language were identified with CDK14 in the clinic-based cohorts (rs705353, P = 1.73 × 10–8) and LINC02712 in the total sample (rs145012974, P = 3.66 × 10–8). GRN (rs5848, P = 4.21 × 10–8) and PURG (rs117523305, P = 1.73 × 10–8) were associated with memory in the total and community-based cohorts, respectively. GWS pleiotropy was observed for language and memory with LOC107984373 (rs73005629, P = 3.12 × 10–8) in the clinic-based cohorts, and with NCALD (rs56162098, P = 1.23 × 10–9) and PTPRD (rs145989094, P = 8.34 × 10–9) in the community-based cohorts. GWS pleiotropy was also found for executive function and memory with OSGIN1 (rs12447050, P = 4.09 × 10–8) and PTPRD (rs145989094, P = 3.85 × 10–8) in the community-based cohorts. Functional studies have previously linked AD to ULK2, NCALD, and PTPRD.ConclusionOur results provide some insight into biological pathways underlying processes leading to domain-specific cognitive impairment and AD, as well as a conduit toward a syndrome-specific precision medicine approach to AD. Increasing the number of participants with harmonized cognitive domain scores will enhance the discovery of additional genetic factors of cognitive decline leading to AD and related dementias.

The Association Between Diabetes Duration and Domain-Specific Cognitive Impairment: A Population-Based Study.

Diabetes is a risk factor for cognitive impairment, and disease duration is associated with geriatric decline and functional disabilities. This study aimed to examine the association of diabetes duration with domain-specific cognitive impairment in elderly. A total of 3,142 participants from the National Health and Nutrition Examination Survey (NHANES) from the period between 2011 and 2014 were included. We assessed cognitive function using the Digit Symbol Substitution Test (DSST), the CERAD Word Learning (CERAD-WL) test, the CERAD Delayed Recall (CERAD-DR) test and animal fluency (AF) test. After adjusting for age, sex, race/ethnicity, education level, and annual household income, we found that diabetes with a duration longer than 20 years were at 3.32-fold increased risk of DSST impairment (OR = 3.32, 95% CI: 1.95 to 5.67), 1.72-fold increased risk of CERAD-WL impairment (OR = 1.72, 95% CI: 1.13 to 2.62), and 1.76-fold increased risk of AF impairment (OR = 1.76, 95% CI: 1.23 to 2.53), compared with those with no diabetes. Associations were generally stronger in women than in men. Participants with diabetes, who were diagnosed at 50-59 years old were at increased risk of DSST impairment, CERAD-WL impairment, CERAD-DR impairment, and AF impairment per 5 years longer duration of diabetes. Longer diabetes duration was associated with the increased risk of cognitive impairment, especially in processing speed and attention. The presence of chronic kidney disease was associated with the increased risk of DSST impairment.

Anatomically interpretable deep learning of brain age captures domain-specific cognitive impairment

The gap between chronological age (CA) and biological brain age, as estimated from magnetic resonance images (MRIs), reflects how individual patterns of neuroanatomic aging deviate from their typical trajectories. MRI-derived brain age (BA) estimates are often obtained using deep learning models that may perform relatively poorly on new data or that lack neuroanatomic interpretability. This study introduces a convolutional neural network (CNN) to estimate BA after training on the MRIs of 4,681 cognitively normal (CN) participants and testing on 1,170 CN participants from an independent sample. BA estimation errors are notably lower than those of previous studies. At both individual and cohort levels, the CNN provides detailed anatomic maps of brain aging patterns that reveal sex dimorphisms and neurocognitive trajectories in adults with mild cognitive impairment (MCI, N = 351) and Alzheimer's disease (AD, N = 359). In individuals with MCI (54% of whom were diagnosed with dementia within 10.9 y from MRI acquisition), BA is significantly better than CA in capturing dementia symptom severity, functional disability, and executive function. Profiles of sex dimorphism and lateralization in brain aging also map onto patterns of neuroanatomic change that reflect cognitive decline. Significant associations between BA and neurocognitive measures suggest that the proposed framework can map, systematically, the relationship between aging-related neuroanatomy changes in CN individuals and in participants with MCI or AD. Early identification of such neuroanatomy changes can help to screen individuals according to their AD risk.