Worse Cognitive Performance Research Articles

COVID-19 and Cognitive and Mental Health During Post-Infection Phase: A Study Among Middle-Aged and Older Indigenous Adults From Brazilian Amazons.

To examine the rate of self-reported coronavirus disease-2019 (COVID-19) and its association with mental and cognitive health during the post-infection phase among middle-aged and older indigenous adults. A cross-sectional study was conducted, including 141 individuals ≥50 and over from an urban indigenous community in Amazonas, Brazil. COVID-19 was deduced from self-reported infections. Cognitive function was evaluated using the Mini-Mental State Exam, Brief Cognitive Screening Battery (BCSB), and language fluency tests. Meanwhile, mental health was assessed through validated scales examining happiness, stress, and depression symptoms. The association between the rate of COVID-19 and cognitive and mental well-being was analyzed using logistic and linear regressions, adjusted for covariates. From March 2020 to February 2022, 65.2% of the urban indigenous group tested positive for COVID-19. Lower functional capacity decreased the odds of contracting COVID-19 (p = .03). Adjusted linear regression models showed that COVID-19 was associated with higher BCSB learning (p = .017) and delayed recall (p = .028). Women, higher age, lower functional capacity, and hospitalization were associated with worse cognitive performance (p < .05). No impact of mental health indicators on past COVID-19 infection was noted. COVID-19 was prevalent among urban Indigenous Brazilians. Unexpectedly, it was linked to enhanced learning and memory, not mental health issues. Cognitive performance was lower for men, older individuals, those with less functional ability, and hospitalized patients, indicating that participant characteristics and disease severity affect the COVID-19 and cognition relationship. Longitudinal studies across diverse Indigenous communities are necessary to understand COVID-19's impact on their cognitive and mental health.

Cognitive dysfunction in de novo Parkinson disease: Remitting vs. progressive cognitive impairment

IntroductionParkinson's disease (PD) exhibits divergent cognitive trajectories; however, the factors contributing to these variations remain elusive. This study aimed to examine the clinical features of patients with different long-term cognitive trajectories in de novo PD over a five-year follow-up. MethodsWe analyzed 258 patients who completed every annual evaluation for five years. According to the Montreal Cognitive Assessment (MoCA) scores, we classified patients into three groups: cognitively normal (n = 118, CN), remitting MoCA decline (n = 74, RMD), and progressive MoCA decline (n = 66, PMD). ResultsThe RMD group was associated with lower olfactory scores (Odds Ratio (OR) = 0.958, p = 0.040), whereas PMD was associated with higher depression scores (OR = 1.158, p = 0.045), probable RBD (OR = 3.169, p = 0.002), older age (OR = 1.132, p < 0.001) and lower educational attainment (OR = 0.828, p = 0.004). PMD had higher neurofilament light chain protein values than CN and RMD (p = 0.006, 0.015, respectively). Longitudinally, PMD showed a greater decline in all cognitive scores and hippocampus volumes (p = 0.004). Meanwhile, RMD exhibited intermediate cognitive and volumetric trajectories between CN and PMD and displayed worse score changes in memory tasks than CN. ConclusionsWhile PMD exhibited known risk factors for cognitive impairment, along with worse cognitive performance and hippocampal volume decline, RMD displayed baseline lower olfactory scores and intermediate cognitive and hippocampal volume decline between the two groups. These findings suggest individuals in RMD may still be at risk for cognitive deficits. However, further long-term follow-up data are needed to unravel the determinants and dynamics of cognitive functions.

Choline kinase alpha genotype is related to hippocampal brain volume and cognition in postmenopausal women

This study examined how single nucleotide polymorphisms (SNPs) related to choline synthesis and metabolism, processes largely regulated by estrogen, influenced hippocampal volume and neuropsychological function following menopause. We investigated the effect of choline kinase alpha (CHKA) genotype on brain volume and neuropsychological performance in postmenopausal women. The effect alleles of certain CHKA SNPs (rs6591331 T, rs10791957 A) are associated with varied responses to choline deficiency and delegation of choline to physiological pathways. The presence of these alleles was hypothesized to correlate with worse cognitive performance in women after menopause. Results from structural MRI scans revealed larger right hippocampal volumes in subjects with a T/T CHKA rs6591331 genotype compared to A/A subjects. Delayed memory scores from the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) were lower in subjects with T/T genotypes compared to those with the A/T genotype and the A/A genotype. Based on these findings, we proposed a CHKA-dependent mechanism present within the brain to compensate for the decreased estrogen and biosynthesized choline associated with menopause.

BIOPSYCHOSOCIAL DETERMINANTS OF COGNITIVE FUNCTION AMONG BLACK OLDER ADULTS

Abstract Black older adults in the United States have twice the risk of being diagnosed with Alzheimer’s disease and related dementias than their white counterparts. However, there remains a gap in knowledge of which factors may contribute to this disparity as well as mechanisms that either increase or decrease risk for poor cognitive outcomes, specifically in older Black adults. This presentation will highlight recent interdisciplinary population health research on the biopsychosocial determinants of cognitive function among Black adults 65 years and older in the Health and Retirement Study. Using within-group regression analyses, studies examine associations between multiple measures across neighborhood, psychosocial, and biomarker domains with cognitive function, measured by Telephone Interview for Cognitive Status scores (range: 0-35) which captures memory and overall mental status. We find that high neighborhood disorder and low social cohesion were associated with worse cognitive function, especially for more highly educated Black older adults and those living in urban communities. Greater frequency of experiences of everyday discrimination among Black older adults was also related to lower cognitive function. Volunteering and having a high sense of purpose in life were associated with better cognitive function for older Black men and women, while being physical active was associated with increased cognitive function for older Black women. C-reactive protein, a measure of systemic inflammation, was positively associated with cognitive function. Overall, this body of work demonstrates the need to further critically assess both risk and resilience processes underlying cognitive function among older Black adults towards reducing current cognitive health inequities.

MODELING HETEROGENEITY IN COGNITIVE TRAJECTORIES IN THE FRAMINGHAM HEART STUDY

Abstract The prevalence of cognitive impairment in the population is growing. Maintaining good cognitive health is central to successful aging, independence, and well-being. Although older age is generally associated with worse cognitive function, there are substantial heterogeneities in the rate of cognitive decline across different cognitive domains and in terms of the clinical onset age of dementia. Recently, harmonized factor scores measuring global cognitive function for the memory, executive function, and language domains have been created in the Framingham Heart Study (FHS). In this work, we identified FHS participants with two or more repeated factor scores after the age of 60 (n=2339; 57% female; 17% APOE-ϵ4 carriers; 64% attended colleges) and were dementia-free at the baseline visits. We fitted latent class mixed models (LCMM) to cluster cognitive trajectories from all three domains using the harmonized factor scores. Non-linear trends with age in the trajectories were modeled via piecewise linear LCMM models followed by stepwise selections to select cluster-specific change points. We identified different latent classes of participants, some characterized by an early cognitive decline before age 70 as compared to late decliners, across different domains. Using 10-fold cross-validation, we also showed that the subgroupings of participants are stable. Our findings indicate class-related differential patterns in cognitive aging in the FHS. Future associations between the identified subclasses, cognitive outcomes, and physical or biological markers may advance the knowledge of multiple pathways of cognitive aging.

ASSOCIATIONS OF PLASMA GDF15 WITH PHYSICAL PERFORMANCE AND COGNITIVE FUNCTIONS IN OLDER ADULTS

Abstract Background Growth differentiation factor 15 (GDF15) has been associated with several age-related disorders, but its associations with functional abilities in community-dwelling older adults are not well studied. Methods The study was a secondary analysis on 1096 community-dwelling older adults (aged 69 to 94 years) recruited from the Multidomain Alzheimer’s Preventive Trial. Plasma GDF15 was measured one year after participants’ enrolment. Annual data of physical performance (grip strength and short physical performance battery [SPPB]) and global cognitive functions (mini-mental state examination [MMSE] and a composite cognitive score) were measured for four years. Adjusted mixed-effects linear models were performed for cross-sectional and longitudinal association analyses. Results A higher GDF15 was cross-sectionally associated with a weaker grip strength (β = -1.1E-03, 95%CI [-2.0E-03, -1.5E-04]), a lower SPPB score (β = -3.1E-04, 95%CI [-5.4E-04, -9.0E-05]) and worse cognitive functions (β = -2.4E-04, 95%CI [-3.3E-04, -1.6E-04] for composite cognitive score; β = -4.0E-04, 95%CI [-6.4E-04, -1.6E-04] for MMSE). Participants with higher baseline GDF15 demonstrated greater longitudinal declines in SPPB (β = -1.0E-04, 95%CI [-1.7E-04, -2.0E-05]) and composite cognitive score (β = -2.0E-05, 95%CI [-4.0E-05, -3.6E-06]). The optimal initial GDF15 cutoff values for identifying participants with minimal clinically significant decline after one year were 2189 pg/mL for SPPB (AUC: 0.580) and 2330 pg/mL for composite cognitive score (AUC: 0.587). Conclusions Plasma GDF15 is cross-sectionally and longitudinally associated with lower-limb physical performance and global cognitive function in older adults. Circulating GDF15 alone has limited capacity of discriminating older adults who will develop clinically significant functional declines.

THE RELATIONSHIP BETWEEN HURRICANE STRESSORS AND COGNITION IN PUERTO RICAN OLDER ADULTS

Abstract Acute and chronic stress exposure negatively impact cognition in older adults. There is little research on this relationship within the context of an acute disaster. This presentation explores the relationship between perceived stress, hurricane stressors, subjective cognition, and cognition in Puerto Rican older adults post-Hurricane Maria. 613 Puerto Rican older adults completed Wave 3 measures for the longitudinal PREHCO study. Perceived stress was measured via a 4-item version of the Perceived Stress Scale. Hurricane stressors were classified as three factors: Home Damage, Family/Friends Network, and Work/Health. Subjective cognition was measured by asking the participant to rate their memory based on a 5-point Likert scale. Cognition was measured via the Telephone Interview for Cognitive Status assessment and the Minimental Cabán. Analyses included two multiple linear regressions with cognitive status and cognitive functioning as the outcomes, respectively, while controlling for age, depressive symptoms, education, gender, and race. There was a significant relationship between higher concern for others post-hurricane and worse generalized cognitive functioning (p&amp;lt;0.05, t=-2.04). Higher levels of cognitive status were significantly associated with better perceptions of memory function (p= 0.015, t=-2.43). Yet higher levels of perceived stress were significantly associated with worse perceptions of memory function (p&amp;lt;0.001, t=7.037). Older adult Puerto Ricans presented with worse cognitive functioning when they were worried about their loved ones’ well-being. Even those who maintained an intact cognitive status believed their memory was worse when they were experiencing more stress. This highlights the importance of differentiating the impact of stress on cognitive ability from subjective cognition.

Association between kidney measurements and cognitive performance in patients with ischemic stroke

Background Individuals with chronic kidney disease (CKD) are at a substantially higher risk for stroke, which may predispose individuals to cognitive impairment. However, the association of low estimated glomerular filtration rate (eGFR) and albuminuria with poorer cognitive performance in patients with stroke is not fully understood, and the current evidence for this association is contradictory. Our aim was to retrospectively investigate whether low eGFR and albuminuria, as indicated by the urine albumin-creatinine ratio (UACR), are independently or jointly associated with worse cognitive performance in patients with ischemic stroke. Methods This retrospective study included 608 patients with acute ischemic stroke. Their UACR and eGFR values were obtained from inpatient medical records. Global cognitive function was assessed with the mini-mental state exam (MMSE) and Montreal Cognitive Assessment (MoCA) one month after hospital discharge. The relationship between renal measures and cognitive performance was assessed using univariate and multiple linear regression analyses. Potential confounders included age, gender, BMI, education, diabetes and hypertension history, NIHSS score, smoking and alcohol consumption status, serum total cholesterol, triglyceride, fasting glucose, uric acid, homocysteine, systolic blood pressure, and either eGFR or UACR. Results Patients had an average age of 66.6±4.1 years, and 48% were females. Average eGFR and UACR were 88.4±12.9 ml/min/1.73m2 and 83.6±314.2 mg/g, respectively. The number of patients with eGFR ≥90, 60–89, and &lt;60 ml/min/1.73 m2 was 371 (61%), 207 (34%), and 30 (5%), respectively, and the percentage of patients with UACR &lt;30 mg/g, 30–300 mg/g, and &gt;300 mg/g was 56%, 39%, and 5%, respectively. Multivariate adjusted models showed that eGFR was independently associated with MMSE (β = -0.4; 95% CI = -0.5,-0.4; p &lt;0.001) and MoCA (β = -0.6; 95% CI = -0.7,-0.5; p &lt;0.001). However, UACR was not significantly correlated with MMSE or MoCA. Conclusion In patients with ischemic stroke, reduced eGFR but not albuminuria was associated with lower cognitive performance. These results show that the eGFR decline could be an effective indicator of cognitive impairment after a stroke. Therefore, regular monitoring and early detection of mild renal dysfunction in patients with acute ischemic stroke might be needed.

Subjective cognitive complaints in patients with progressive supranuclear palsy.

Subjective cognitive complaints (SCC) refer to self-reported cognitive decline that may or may not be reflected in objective neuropsychological evaluations. Such SCC are prevalent in neurodegenerative diseases, including Parkinson's disease (PD), but the prevalence and clinical features in patients with progressive supranuclear palsy (PSP) have not been investigated. We recruited 83 PSP patients without dementia and investigated their SCC using a semi-structured interview. Comprehensive neuropsychological test results and patient clinical features were compared according to presence of SCC and underlying cognitive state. Among the 83 patients, 16 had normal cognition (NC), 67 had mild cognitive impairment (MCI), and 36 (43.4%) reported SCC. Among NC patients, 37.5% (6/16) had SCC, while 44.8% (30/67) of MCI patients reported SCC. There were no differences between the neuropsychological test results or demographic and clinical characteristics of PSP patients with or without SCC in the NC group. The demographic and clinical characteristics of the MCI+SCC (MCI with SCC)and MCI-SCC (MCI without SCC) groups were comparable, but the MCI+SCC group had significantly worse neuropsychological scores than the MCI-SCC group, particularly in tests assessing attention, language, visual memory, and fronto-executive function domains. While SCC are commonly reported by PSP patients, patients with PSP and MCI+SCC had worse cognitive function than those who did not report SCC. These findings suggest that SCC in PSP patients with MCI could be a worsening sign of cognitive function. Therefore, it is crucial for physicians to assess SCC in PSP patients and to provide timely diagnosis and management of cognitive decline.

Predictors of executive function among 2 year olds from a Thai birth cohort

Executive function (EF) is a critical skill for academic achievement. Research on the psychosocial and environmental predictors of EF, particularly among Southeast Asian, agricultural, and low income/rural populations, is limited. Our longitudinal study explored the influence of agricultural environmental, psychosocial, and temperamental factors on children’s emerging EF. Three-hundred and nine farm worker women were recruited during the first trimester of pregnancy. We evaluated the effects of prenatal insecticide exposure and psychosocial factors on “cool” (i.e., cognitive: A-not-B task, looking version) and “hot” EF (i.e., affective, response inhibition) measures of emerging EF. Maternal urine samples were collected monthly during pregnancy, composited, and analyzed for dialkylphosphate (DAP) metabolites of organophosphate insecticides. Psychosocial factors included socioeconomic status, maternal psychological factors, and quality of mother-child behavioral interactions. Backward stepwise regressions evaluated predictors of children’s EF at 12 (N = 288), 18 (N = 277) and 24 (N = 280) months of age. We observed different predictive models for cool EF, as measured by A-not-B task, vs. hot EF, as measured by response inhibition tasks. Report of housing quality as a surrogate for income was a significant predictor of emerging EF. However, these variables had opposite effects for cool vs. hot EF. More financial resources predicted better cool EF performance but poorer hot EF performance. Qualitative findings indicate that homes with fewer resources were in tribal areas where children must remain close to an adult for safety reasons. This finding suggests that challenging physical environments (e.g., an elevated bamboo home with no electricity or running water), may contribute to development of higher levels of response inhibition through parental socialization methods that emphasize compliance. Children who tended to show more arousal and excitability, and joy reactivity as young infants in the laboratory setting had better cognitive performance. In contrast, maternal emotional availability was a significant predictor of hot EF. As expected, increased maternal exposure to pesticides during pregnancy was associated with worse cognitive performance but was not associated with inhibitory control. Identifying risk factors contributing to the differential developmental pathways of cool and hot EF will inform prevention strategies to promote healthy development in this and other unstudied rural, low income Southeast Asian farming communities.

Altered brain activity and cognitive impairment in patients with psoriasis.

Patients with psoriasis may have cognitive impairment. However, there is limited information regarding intrinsic brain activity and cognitive function in patients with psoriasis. This study aim to assess alterations of intrinsic brain activity and its association with cognitive function in patients with psoriasis. A total of 222 patients with psoriasis aged 18-70 years and 144 age and gender-matched healthy controls (HCs) were enrolled into this study. All subjects underwent brain resting-state functional magnetic resonance imaging (rs-fMRI) and neuropsychological testing. The rs-fMRI data were analysed for both intrinsic brain activity as indicated by amplitude of low-frequency fluctuation (ALFF) and seed-based functional connectivity (FC). Correlative analysis of brain activity with cognitive assessment was performed. Compared with the HCs, patients with psoriasis had worse cognitive performance in the Trail Making Test, Digit Span Test and Stroop Color-Word Test (p < 0.05). Patients with psoriasis showed decreased ALFF in the left superior frontal gyrus, the left medial superior frontal gyrus and the right precuneus gyrus; as well as enhanced ALFF in the left paracentral lobule (pFWE < 0.05). Significant correlations were noted between the altered ALFF in the four brain regions and cognitive assessment (p < 0.05). Moreover, patients with psoriasis had increased FC between the four brain regions with altered ALFF (seeds) and the left prefrontal gyrus, the left anterior cingulate gyrus, left superior parietal lobule and default mode network (DMN) regions such as the right precuneus gyrus, left inferior parietal lobule, right angular gyrus and bilateral inferior temporal gyrus (pFWE < 0.05). Patients with psoriasis had altered brain activity and connectivity in the key brain areas within the DMN-prefrontal circuit. These brain changes may be the underlying neural correlates for cognitive functioning in patients with psoriasis.

Brain Dynamics Complexity as a Signature of Cognitive Decline in Parkinson's Disease.

Higuchi's fractal dimension (FD) captures brain dynamics complexity and may be a promising method to analyze resting-state functional magnetic resonance imaging (fMRI) data and detect the neuronal interaction complexity underlying Parkinson's disease (PD) cognitive decline. The aim was to compare FD with a more established index of spontaneous neural activity, the fractional amplitude of low-frequency fluctuations (fALFF), and identify through machine learning (ML) models which method could best distinguish across PD-cognitive states, ranging from normal cognition (PD-NC), mild cognitive impairment (PD-MCI) to dementia (PDD). Finally, the aim was to explore correlations between fALFF and FD with clinical and cognitive PD features. Among 118 PD patients age-, sex-, and education matched with 35 healthy controls, 52 were classified with PD-NC, 46 with PD-MCI, and 20 with PDD based on an extensive cognitive and clinical evaluation. fALFF and FD metrics were computed on rs-fMRI data and used to train ML models. FD outperformed fALFF metrics in differentiating between PD-cognitive states, reaching an overall accuracy of 78% (vs. 62%). PD showed increased neuronal dynamics complexity within the sensorimotor network, central executive network (CEN), and default mode network (DMN), paralleled by a reduction in spontaneous neuronal activity within the CEN and DMN, whose increased complexity was strongly linked to the presence of dementia. Further, we found that some DMN critical hubs correlated with worse cognitive performance and disease severity. Our study indicates that PD-cognitive decline is characterized by an altered spontaneous neuronal activity and increased temporal complexity, involving the CEN and DMN, possibly reflecting an increased segregation of these networks. Therefore, we propose FD as a prognostic biomarker of PD-cognitive decline. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Association between Aluminium Levels and Cognitive Decline in Environmentally Exposed Elders

AbstractBackgroundNormal brain functioning depends on metals homeostasis, as imbalances may increase oxidative stress and cause other detrimental intracellular events that lead to cell loss. Furthermore, environmental exposure to toxic metals is hypothesized to induce neuroinflammation and neuropathology, paving the way to neurodegeneration. The aim of this study was to examine whether such Potentially Toxic Elements (PTE) are associated with cognitive performance over time in a sample of elderly individuals of environmentally contaminated regions.MethodA total of 146 elders permanently residing in environmental risk areas were recruited. Participants completed the Mini Mental State Examination (MMSE) for cognitive assessment and were biomonitored for several PTE through hair and urine analysis. After 5 years, the cognitive assessment was repeated.ResultCognitive performance significantly declined from baseline to follow‐up (p &lt; 0.001), with participants scoring on average 4.41 less points on MMSE (Baseline: M = 25.79, SD = 3.520, Md = 27.00; Follow‐up: M = 21.38, SD = 5.343, Md = 21.00). Regression analysis on the relationship between PTE and cognitive performance revealed that Aluminium (β = ‐0.322, p = 0.32) and Zinc (β = ‐0.372, p = 0.15) in hair and Aluminium in urine (β = ‐0.368, p = 0.010) significantly predicted MMSE scores past 5 years of biomonitoring (p = 0.002). Higher contents of these PTE were associated with worse cognitive performance at follow‐up, after controlling the effects of age, education and supplement intake.ConclusionHigher levels of Aluminium significantly predict worse general cognitive performance 5 years after biomonitoring across different biological samples. Environmental exposure to this metal may constitute a risk factor for cognitive decline.

Fear and avoidance of memory loss: associations with cognitive, psychological and lifestyle factors in mid‐ and later life

AbstractBackgroundAlzheimer’s disease and related dementias (ADRD) are among the most feared conditions. Some level of fear can motivate healthy behaviors. However, intense fears can have the opposite effect, leading to avoidance behaviors such as withdrawal from cognitively or socially demanding activities. In this way, fears and avoidance behaviors have potential to influence modifiable ADRD risk. Here, we investigated if fear and avoidance are associated with cognitive, psychological and lifestyle factors in mid‐ and later life.MethodsParticipants were middle‐aged (n = 188, 40‐59 years, mean = 51.4 ± 5, 52.7% female) and older adults (n = 746, 60‐90 years, mean = 65 ± 7.2, 61.5% female). Fears and avoidance behaviors were measured using Fear and Avoidance of Memory Loss scale. Linear regression examined the contribution of fear and avoidance to cognitive, psychological and lifestyle factors. Mid‐life factors included cognition (COGNITO), stress (Perceived Stress Scale), depressive symptoms (Center for Epidemiologic Studies Depression Scale), loneliness (UCLA Loneliness Scale) and lifestyle activities (Lifetime of Experiences Questionnaire). Later life factors included cognition (MoCA) and depression (Geriatric Depression Scale). Models were adjusted for age, gender, education, ADRD family history and anxiety.ResultsMiddle‐aged and older women reported higher fear compared to men (ps &lt; .028). Older individuals with a family history of ADRD also reported higher fear (p &lt; .001). Avoidance behaviors were significantly associated with worse cognitive performance in later life (β = ‐0.10, p = .020), but not in mid‐life. Greater avoidance in mid‐life was associated with higher stress (β = .83, p = .001), loneliness (β = 1.22, p &lt; .001) and depressive symptoms (β = 1.09, p &lt; .001), and lower engagement in lifestyle activities (β = ‐0.19, p = .02). Avoidance was also associated with depressive symptoms in later life (β = .28, p &lt; .001).ConclusionsAvoidance behaviors were associated with lower engagement in healthy lifestyle activities in mid‐life, worse cognitive performance in later life, and reduced psychological well‐being in both mid‐ and later life. While causation cannot be determined, it is likely that these factors interact recursively over time. Thus, targeting avoidance early on may be beneficial for ADRD risk reduction.

Bowel movement frequency, the gut microbiome, and cognitive function in women and men

AbstractBackgroundBowel movement frequency and the gut microbiome may be associated with the risk of dementia.MethodWe examined the association between bowel movement frequency and cognitive function in 112,753 women and men from Nurses’ Health Study (NHS), Nurses’ Health Study II (NHSII), and Health Professionals Follow‐Up Study (HPFS) and explored the role of the gut microbiome in explaining these associations in a sub‐cohort of 515 NHSII and HPFS participants. We collected data on bowel movement frequency in 2012/13 and subjective cognitive function from 2014 to 2017 in all participants and objective cognitive function using a neuropsychological battery between 2014 and 2018 in 12,696 NHSII participants. We profiled the gut microbiome using shotgun metagenomics.ResultBowel movement frequency was associated with overall objective cognitive function and learning and working memory in an inverse J‐shape dose‐response manner (both Pnon‐linearity&lt;0.05). Compared to those with once daily bowel movements, participants with bowel movement frequency of every 3+ days had significantly worse cognition, equivalent to 3.0 (95% confidence interval (CI),1.2, 4.7) years of additional aging. We observed similar J‐shape dose‐response relationships of bowel movement frequency with the odds of subjective cognitive decline and the likelihood of having more subjective cognitive complaints over time. Bowel movement frequencies of every 3+ days and ≥twice /day, compared to once daily bowel movement, were associated with odds ratios of subjective cognitive decline of 1.73 (95% CI, 1.60, 1.86) and 1.37 (95% CI, 1.33, 1.44), respectively. These relationships were generally consistent across three cohorts and subgroups. Bowel movement frequency and subjective cognition were significantly associated with the overall variation of the gut microbiome (both P &lt;0.005) and specific microbial species. Butyrate producers were depleted in those with less frequent bowel movements and worse cognitive function, while a higher abundance of dysbiosis‐related, pro‐inflammatory species was associated with bowel movement frequency of ≥twice/day and worse cognitive function.ConclusionLess frequent bowel movements were associated with worse cognitive function. The gut microbiome may be a mechanistic link underlying the association between intestinal motility patterns and cognitive function.

Psycho‐social risk factors for worse cognitive performance in sexual minority older adults

AbstractBackgroundSexual minority older adults (SMOA) may have a greater risk of developing cognitive impairment than heterosexual older adults (HOA), but currently available findings are inconsistent. Minority stress (i.e. sexual orientation‐related stigma) has been suggested to drive worse cognitive health in this population. Therefore, the present study aimed to investigate whether minority stress and other risk factors for worse cognition in SMOA, namely depression and marital status, were associated with worse cognitive performance in SMOA.MethodA total of 336 SMOA and 5561 HOA participants aged 50+, non‐institutionalised and free from neurodegenerative diseases from Wave 6 of the English Longitudinal Study of Ageing were included. Cognitive performance (i.e. temporal orientation, episodic memory and fluid intelligence) of SMOA and HOA was compared using general linear models including age, sex and education as covariates. The impact of depressive symptoms, marital status and minority stress on cognition in the two groups was also investigated. Weighting was performed to correct for sampling probability and differential non‐response.ResultSMOA were more likely to be single and to report stressful social experiences due to sexual orientation than HOA participants. SMOA had better episodic memory than HOA and depressive symptoms and being single were associated with worse cognitive performance across all tests. Associations between cognitive performance and all risk factors were found not to be significantly different between the two groups. However, minority stress was negatively associated (b = ‐2.116, p = 0.016) with fluid intelligence in the SMOA group only.ConclusionConsistently with previous evidence, the SMOA had better episodic memory performance than the HOA group and both more severe depression and not being in a relationship had a generalised detrimental impact on cognition. However, this study provided the first evidence of a potential negative impact of a proxy measure of minority stress on cognitive performance, i.e. worse fluid intelligence, in SMOA. Further investigations are needed to assess minority stress more comprehensively and to clarify the potential mechanisms driving decline in both self‐reported and objectively assessed cognitive health in SMOA.

Increased Genetic Risk for ADHD Potentiates Cognitive Impairment and Brain Hypometabolism in Alzheimer’s Disease Patients

AbstractBackgroundRecent epidemiological studies showed that patients with attention‐deficit/hyperactivity disorder (ADHD) are more likely to be diagnosed with Alzheimer’s Disease (AD). Additionally, increased genetic risk for ADHD, measured with ADHD polygenic risk scores (ADHD‐PRS), was associated with amyloid‐dependent cognitive decline in older adults. However, it is unclear whether higher genetic risk for ADHD is associated with worse cognitive function in patients with AD dementia.MethodWe used data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) to investigate the association between cognitive function (Preclinical Alzheimer Cognitive Composite [PACC], executive function, and memory) and ADHD‐PRS in subjects with AD dementia. Additionally, we tested whether ADHD‐PRS potentiated brain hypometabolism measured with [18F]FDG‐PET. Analyses were controlled by age, sex, years of study, and number of APOE ε4 alleles.ResultWe evaluated baseline data from 264 AD patients (114 women [43.2%], mean [SD] age of 75 [7.6] years). ADHD‐PRS was associated with decreased cognitive function (p‐value = .04, η2 = .01, Figure 1a), more specifically in executive function (p‐value = .04, η2 = .01, Figure 1c). Higher ADHD‐PRS was associated with brain hypometabolism in frontal, parietal, and temporal regions (Figure 2a,b). Brain hypometabolism correlated with worse cognitive function in the following regions: postcentral gyrus (p‐value = .01, η2 = .03), superior parietal gyrus (p‐value = .001, η2 = .07), precentral gyrus (p‐value = .004, η2 = .05), and fusiform gyrus (p‐value&lt;.0001, η2 = .08, Figure 2c,d,e,f). Finally, decreased metabolism in these four regions mediated the effect of ADHD‐PRS on cognitive function (Figure 3).ConclusionFindings indicate that a higher genetic risk for ADHD is correlated with impaired cognitive function with small effect sizes. Moreover, the effects of the genetic risk of ADHD on cognitive function were mediated by hypometabolism in frontal, parietal, and temporal brain regions, which could point to a decrease resilience to AD pathology in individuals with ADHD. Clinically, our findings suggest that patients with comorbid ADHD and AD dementia have a more severe disease phenotype, with potential implications for prognosis and treatment.

Cerebral microbleeds in Down syndrome: association with demographic, genetic, fluid and imaging biomarkers of Alzheimer’s disease

AbstractBackgroundWith the development of amyloid‐modifying therapeutic agents that can lead to cerebral microhaemorrhages, it is critical to meticulously characterise the natural history of cerebral microbleeds (MBs) in populations genetically predisposed to develop Alzheimer’s disease (AD), such as Down syndrome (DS). We aimed to investigate MB prevalence in a large cohort of adults with DS and define associations with demographic, genetic, fluid and imaging biomarkers of AD, and cognitive performance.MethodsCross‐sectional design. Adults with DS and euploid controls from the Down Alzheimer Barcelona Neuroimaging Initiative underwent a 3T‐MRI protocol, including susceptibility‐weighted imaging (SWI) acquisition. Manual tracing of MBs was performed by two independent raters using ITK‐SNAP. Participants were classified according to MB status (MB‐/MB+) and severity (0, 1, 2+ MBs). Non‐parametric statistical tests were used to assess the effect of MBs on demographic, clinical, genetic, CSF and neuroimaging AD biomarkers, and cognitive tests.ResultsWe included 247 participants with DS along the AD continuum, and 167 euploid controls (Table 1). The proportion of MB+ was higher in DS participants than controls, and progressively increased with AD clinical stages and age in the DS group (Fig. 1). By contrast, MB status did not differ by APOEε4 status, intellectual disability, or sex. In DS, the MB+ group had increased white matter hyperintensity volume and decreased hippocampal volumes compared to MB‐. DS MB+ also had lower CSF Aβ42/40 ratio, higher CSF t‐tau and p‐tau‐181 concentrations, and tended toward worse cognitive performance. Most effects gradually evolved with MB severity, although significant differences were mainly between MB‐ vs MB 2+ (Fig. 2). Finally, sensitivity analyses showed that most results became non‐significant when comparing DS MB+ to a 1:1 DS MB‐ group matched for age, sex, intellectual disability and/or AD diagnosis.ConclusionMB presence and severity are increased in adults with DS, and worsen with clinical progression and AD pathology. Yet, matched group analyses suggest that MB have limited impact on cognition and neurodegeneration. These results provide better characterisation of the presence and effect of MB in a population with an ultra‐high risk of developing AD who could benefit from new disease modifying drugs.

A brief questionnaire of self‐reported cognitive decline predicts MMSE and study partner QDRS: findings from the Davis Memory and Aging Cohort at Mass General Brigham

AbstractBackgroundA brief self‐reported questionnaire to efficiently capture subjective cognitive decline, a stage considered to be between cognitively unimpaired and mild cognitive impairment, could enhance clinical research and practice. We hypothesized that a 3‐question measure of self‐reported cognitive decline is associated with worse cognitive performance and increased functional changes reported by a study partner (SP).MethodThe Davis Memory and Aging Cohort (MAC) at Mass General Brigham recruits individuals 45 years or older with a broad range of cognitive symptoms. Participants answered the following three questions adapted from the NIA‐AA research framework: Q1. “Have you experienced a change in your memory in the last 1‐3 years?” Q2. “Has this been a persistent change over the last 6 months?” Q3. “Are you concerned about this change?” scored on a Likert scale (0‐4), with high scores representing greater decline. Responses to Q2 and Q3 were set to 0 if Q1 = 0. Participants completed the Mini‐Mental State Examination (MMSE; cognitive performance), and SPs completed the Quick Dementia Rating System (QDRS; functional changes). We tested the association between the total BCSS score (Q1+Q2+Q3; predictor) and MMSE or QDRS total scores (outcome) using linear regression controlling for age, sex, and years of education. We then tested these associations in a subgroup without significant SP concern (QDRS&lt;1.5).ResultThere were 399 MAC participants with complete data (mean age = 67.2±8.3, 64% female, Table 1). Based on QDRS cut‐offs, there were 248 cognitively unimpaired participants, 118 with mild cognitive impairment, and 33 with dementia. The total score was associated with lower MMSE (beta = ‐0.30, p&lt;0.001) and higher QDRS (beta = 0.51, p&lt;0.001). Q1 score by itself was associated with lower MMSE (beta = 0.98, p&lt;0.001) and higher QDRS (beta = 1.2, p&lt;0.001) (Figure 1). In a subset with QDRS&lt;1.5 (n = 248), both the total score (beta = ‐0.22, p = 0.002) and Q1 score (beta = ‐0.62, p&lt;0.001) were associated with lower MMSE.ConclusionSelf‐reported cognitive decline was associated with worse global cognition, even among those whose SPs reported no significant functional concerns. Our results suggest that the brief self‐reported questionnaire could be a useful screening tool in research and clinic that efficiently probes cognitive functioning.

Disambiguating the macro‐scale anatomy of dysexecutive and behavioral degenerative diseases of the mind

AbstractBackgroundThere is a longstanding ambiguity regarding the clinical diagnosis of dementia syndromes predominantly targeting executive functions versus behavior/personality. This is due to a lack of knowledge about the macro‐scale anatomy underlying these symptomatologies, a partial overlap in clinical features, and the fact that a single underlying pathology can give rise to both phenotypes and vice‐versa.MethodWe included data from patients with genetic, biomarker, and/or autopsy evidence for fronto‐temporal lobar degeneration (FTLD) diagnosed with behavioral variant fronto‐temporal dementia (bvFTD, n = 30) and patients with biomarker and/or autopsy evidence for Alzheimer’s disease (AD) pathology diagnosed with either an initial and predominant dysexecutive (dAD, n = 52), behavioral (bvAD, n = 7), or amnestic (aAD, n = 28) syndrome. We assessed group‐wise differences in clinical/cognitive features and 18Fluorodeoxyglucose‐positron emission tomography (FDG‐PET) patterns. This was followed by a spectral covariance decomposition between FDG‐PET images to yield latent patterns of relative metabolism (“eigenbrains”). These eigenbrains were subsequently linked to clinical/cognitive data and meta‐analytic topics reflecting a wide range of mental abilities. We used a linear discriminant analysis (LDA) to perform eigenbrain‐based diagnostic predictions.ResultdAD and bvFTD patients were the youngest at symptom onset, followed by bvAD, then aAD. dAD patients had worse cognitive performance on nearly all cognitive domains compared to other groups. Hypometabolism was observed across associative cortices in dAD, temporo‐parietal areas in aAD, and fronto‐temporal areas in bvFTD and bvAD (Fig. 1). The spectral covariance decomposition yielded nine eigenbrains which explained 61% of the variance in patterns of FDG‐PET, and only the first three are presented (Fig. 2). These eigenbrains revealed that relative hypometabolism in association cortices, notably lateral parietal areas, associated with dysexecutive symptomatology and a lower likelihood of behavior/personality problems, whereas relative hypometabolism restricted to frontal and temporopolar areas showed opposite associations. The LDA yielded an accuracy of 82.1% in predicting diagnostic category (Fig. 3).ConclusionThis study suggests distinct macro‐scale underpinnings underlying predominant dysexecutive versus behavioral symptomatology in degenerative dementia phenotypes. This has implication for the implementation of clinical and research criteria for these dementia syndromes and highlights the importance of data‐driven techniques to inform the classification of degenerative diseases.