Non-alcoholic Fatty Liver Disease and Longitudinal Cognitive Changes in Middle-Aged and Elderly Adults

Background and PurposeNon-alcoholic fatty liver disease (NAFLD) and cognitive impairment are common aging-related disorders. This study aims to explore the changes of cognitive function in middle-aged and elderly population with NAFLD from a Jidong impairment cohort.MethodsA total of 1,651 middle-aged and elderly participants (>40 years) without cognitive impairment were recruited into the current study in 2015 and were followed up until to 2019. Abdominal ultrasonography was used for diagnosis of NAFLD. Global cognitive function was assessed with the Mini-Mental State Examination (MMSE). Cognitive impairment was defined as a score <18 for illiterates, a score <21 for primary school graduates, and a score <25 for junior school graduates or above. Multivariable regression analysis was performed to evaluate the association between NAFLD and the four-year cognitive changes.ResultsOut of 1,651 participants, 795 (48.2%) of them had NAFLD in 2015. Cognitive impairment occurred in 241 (14.6%) participants in 2019. Patients with NAFLD had higher 4-year incidence of cognitive impairment than non-NAFLD patients did (17.7 vs. 11.7%, p < 0.001). Multivariable linear regression analysis showed significant association of baseline NAFLD with lower MMSE score in 2019 (β = −0.36, p < 0.05). Multivariable logistic analysis found that the adjusted odds ratio (OR) with 95% confidence interval (CI) of baseline NAFLD was 1.45 (1.00–2.11) for cognitive impairment in 2019 (p = 0.05). We also identified effects of baseline NAFLD on subsequent cognitive impairment as modified by age (interaction p < 0.01) and carotid stenosis (interaction p = 0.05) but not by gender.ConclusionsNAFLD is associated with cognitive decline, especially in middle-aged and with carotid stenosis population.

Comparison of delirium detection tools in acute care

Background Delirium is a frequent psychopathological syndrome in geriatric patients. It is sometimes the only symptom of acute illness and bears a high risk for complications. Therefore, feasible assessments are needed for delirium detection. Objective and methods Rapid review of available delirium assessments based on a current Medline search and cross-reference check with a special focus on those implemented in acute care hospital settings. Results A total of 75 delirium detection tools were identified. Many focused on inattention as well as acute onset and/or fluctuating course of cognitive changes as key features for delirium. A range of assessments are based on the confusion assessment method (CAM) that has been adapted for various clinical settings. The need for a collateral history, time resources and staff training are major challenges in delirium assessment. Latest tests address these through a two-step approach, such as the ultrabrief (UB) CAM or by optional assessment of temporal aspects of cognitive changes (4 As test, 4AT). Most delirium screening assessments are validated for patient interviews, some are suitable for monitoring delirium symptoms over time or diagnosing delirium based on collateral history only. Conclusion Besides the CAM the 4AT has become well-established in acute care because of its good psychometric properties and practicability. There are several other instruments extending and improving the possibilities of delirium detection in different clinical settings.

Association of β-Amyloid Accumulation With Executive Function in Adults With Unimpaired Cognition

Background and Objectives:The neuropathological changes underlying Alzheimer´s disease (AD) start before overt cognitive symptoms arise, but it is not well-known how they relate to the first subtle cognitive changes. The objective for this study was to examine the independent associations of the AD hallmarks β-amyloid (Aβ), tau, and neurodegeneration with different cognitive domains in cognitively unimpaired (CU) individuals.Methods:In this cross-sectional study, CU participants from the prospective BioFINDER-2 study were included. All had CSF biomarkers (Aβ42 and P-tau181), MRI (cortical thickness of AD-susceptible regions), Aβ-PET (neocortical uptake), tau-PET (entorhinal uptake), and cognitive test data for i) memory, ii) executive function, iii) verbal function, iv), and visuospatial function. Multivariable linear regression models were performed, using either CSF Aβ42, P-tau181 and cortical thickness or Aβ-PET, tau-PET, and cortical thickness, as predictors of cognitive function. The results were validated in an independent cohort (ADNI).Results:316 CU participants were included from the BioFINDER-2 study. Abnormal Aβ-status was independently associated with the executive measure, regardless of modality (CSF Aβ42 β=0.128, p=0.024; Aβ-PET β=0.124, p=0.049), while tau was independently associated with memory (CSF P-tau181 β=0.132, p=0.018; tau-PET β=0.189, p=0.002). Cortical thickness was independently associated with the executive measure and verbal fluency in both models (p=0.005-0.018). To examine the relationships in the earliest stage of preclinical AD, only participants with normal biomarkers of tau and neurodegeneration were included (n=217 CSF-based; n=246 PET-based). Again, Aβ-status was associated with executive function (CSF Aβ42, β=0.189, p=0.005; Aβ-PET, β=0.146, p=0.023), but not with other cognitive domains. The results were overall replicated in the ADNI cohort (n=361).Discussion:These findings suggest that Aβ is independently associated with worse performance on an executive measure but not with memory performance, which instead is associated with tau pathology. This may have implications for early preclinical AD screening and outcome measures in AD trials targeting Aβ pathology.

Cognitive Sequelae of Silent Ischemic Lesions Following Carotid Artery Stenting: Possible Role of Age-Related Moderation

Background: The occurrence of ischemic lesions is common in patients receiving carotid artery stenting (CAS), and most of them are clinically silent. However, few studies have directly addressed the cognitive sequelae of these procedure-related silent ischemic lesions (SILs).Objective: In this study, we attempted to investigate the effects of SILs on cognition using a comprehensive battery of neuropsychological tests.Method: Eighty-five patients with unilateral carotid stenosis and 25 age-matched healthy volunteers participated in this study. Brain MRI was performed within 1 week before and 1 week after CAS to monitor the occurrence of post-CAS SILs. A comprehensive battery tapping reading ability, verbal and non-verbal memory, visuospatial function, manual dexterity, executive function, and processing speed was administered 1 week before and 6 months after CAS. To control for practice effects on repeated cognitive testing, the reliable change index (RCI) derived from the healthy volunteers was used to determine the cognitive changes in patients with carotid stenosis.Results: Among the 85 patients with carotid stenosis, 21 patients received medical treatment (MED group), and procedure-related SILs were noted in 17 patients (SIL+ group) but not observed in 47 patients (SIL– group) after undergoing CAS. Two-way (group × phase) ANOVA revealed that the volunteer group showed improved scores in most cognitive tests while only limited improvement was noted in the SIL– group. The MED and control groups tended to show improvement in the follow-up cognitive testing than the SIL+ group. However, most of the cognitive changes for each patient group did not exceed the upper or lower limits (z = ±1.0) of the RCI.Conclusions: Although the occurrence of procedure-related SILs is common in patients undergoing CAS, their impacts on cognitive changes after CAS may be limited. The practice effect should be taken into consideration when interpreting cognitive changes following CAS.

Trials and Treatments for Vascular Brain Health: Risk Factor Modification and Cognitive Outcomes

There is robust evidence linking vascular health to brain health, cognition, and dementia. In this article, we present evidence from trials of vascular risk factor treatment on cognitive outcomes. We summarize findings from randomized controlled trials of antihypertensives, lipid-lowering medications, diabetes treatments (including antidiabetic drugs versus placebo, and intensive versus standard glycemic control), and multidomain interventions (that target several domains simultaneously such as control of vascular and metabolic factors, nutrition, physical activity, and cognitive stimulation etc). We report that evidence on the efficacy of vascular risk reduction interventions is promising, but not yet conclusive, and several methodological limitations hamper interpretation. Evidence mainly comes from high-income countries and, as cognition and dementia have not been the primary outcomes of many trials, evaluation of cognitive changes have often been limited. As the cognitive aging process occurs over decades, it is unclear whether treatment during the late-life window is optimal for dementia prevention, yet older individuals have been the target of most trials thus far. Further, many trials have not been powered to explore interactions with modifiers such as age, race, and apolipoprotein E, even though sub-analyses from some trials indicate that the success of interventions differs depending on patient characteristics. Due to the complex multifactorial etiology of dementia, and variations in risk factors between individuals, multidomain interventions targeting several risk factors and mechanisms are likely to be needed and the long-term sustainability of preventive interventions will require personalized approaches that could be facilitated by digital health tools. This is especially relevant during the coronavirus disease 2019 (COVID-19) pandemic, where intervention strategies will need to be adapted to the new normal, when face-to-face engagement with participants is limited and public health measures may create changes in lifestyle that affect individuals’ vascular risk profiles and subsequent risk of cognitive decline.

Toward the Decipherment of Molecular Interactions in the Diabetic Brain

Diabetes mellitus (DM) has been associated with cognitive complications in the brain resulting from acute and chronic metabolic disturbances happening peripherally and centrally. Numerous studies have reported on the morphological, electrophysiological, biochemical, and cognitive changes in the brains of diabetic individuals. The detailed pathophysiological mechanisms implicated in the development of the diabetic cognitive phenotype remain unclear due to intricate molecular changes evolving over time and space. This review provides an insight into recent advances in understanding molecular events in the diabetic brain, focusing on cerebral glucose and insulin uptake, insulin action in the brain, and the role of the brain in the regulation of glucose homeostasis. Fully competent mitochondria are essential for energy metabolism and proper brain function; hence, the potential contribution of mitochondria to the DM-induced impairment of the brain is also discussed.

Unsupervised high-frequency smartphone-based cognitive assessments are reliable, valid, and feasible in older adults at risk for Alzheimer disease.

Smartphones have the potential for capturing subtle changes in cognition that characterize preclinical Alzheimer disease (AD) in older adults. The Ambulatory Research in Cognition (ARC) smartphone application is based on principles from ecological momentary assessment (EMA) and administers brief tests of associative memory, processing speed, and working memory up to 4 times per day over 7 consecutive days. ARC was designed to be administered unsupervised using participants’ personal devices in their everyday environments. We evaluated the reliability and validity of ARC in a sample of 268 cognitively normal older adults (ages 65-97) and 22 individuals with very mild dementia (ages 61-88). Participants completed at least one 7-day cycle of ARC testing and conventional cognitive assessments; most also completed cerebrospinal fluid, amyloid and tau PET, and structural MRI studies. First, results indicated that ARC tasks were reliable as between person reliability across the 7-day cycle and test-retest reliabilities at 6-month and 1-year follow-ups all exceeded 0.85. Second, ARC demonstrated construct validity as evidenced by correlations with conventional cognitive measures (r = 0.53 between composite scores). Third, ARC measures correlated with AD biomarker burden at baseline to a similar degree as conventional cognitive measures. Finally, the intensive 7-day cycle indicated that ARC was feasible (86.50% approached chose to enroll), well tolerated (80.42% adherence, 4.83% dropout), and was rated favorably by older adult participants. Overall, the results suggest that ARC is reliable and valid and represents a feasible tool for assessing cognitive changes associated with the earliest stages of AD.

Assessment of Psychological Stress Associated with COVID-19 Lockdown in the Urban Adult Population of India

Background: COVID-19, the unprecedented deadly pandemic has turned the world topsy-turvy. It has affected all the people like poor and rich, young and old, educated and uneducated, male and female with detrimental consequences. People who are in quarantine and/or lockdown are likely to develop a wide range of symptoms like psychological stress, irritability, anxiety, depression etc. Hence, this study was undertaken to assess the psychological effects of COVID-19 lockdown among adult population residing in Chennai, India. This study is a cross sectional descriptive study carried out in Chennai, India. A structured questionnaire was developed containing 25 questions related to the emotional disturbance, depression, self-concept, physical problems, cognitive changes and role performance and 7 questions related to the demographics. An online survey was conducted using a structured questionnaire using a non-probability snowball sampling technique. A total of 579 responses were received. The findings of the present study revealed that, among 579 respondents, more than half of the respondents 320(56.3%)were under severe psychological stress, 192(33.2%) respondents that is one third of the people had moderate psychological stress and remaining were having mild psychological stress. The study also revealed that there was a statistically significant association of psychological problems associated with demographic variables. Our Study revealed that people living in Chennai had severe psychological problem due to theCOVID-19 lockdown. This highlights the importance and immediate need for the development special intervention programmes for the people with psychological problems due to the COVID-19 lockdown.

Sleep Polygenic Risk Score Is Associated with Cognitive Changes over Time

Sleep problems have been associated with cognition, both cross-sectionally and longitudinally. Specific genes have been also associated with both sleep regulation and cognition. In a large group of older non-demented adults, we aimed to (a) validate the association between Sleep Polygenic Risk Score (Sleep PRS) and self-reported sleep duration, and (b) examine the association between Sleep PRS and cognitive changes in a three-year follow-up. Participants were drawn from the Hellenic Longitudinal Investigation of Aging and Diet (HELIAD). A structured, in-person interview, consisting of a medical history report and physical examination, was conducted for each participant during each of the visits (baseline and first follow-up). In total, 1376 participants were included, having all demographic, genetic, and cognitive data, out of which, 688 had at least one follow-up visit. In addition, an extensive neuropsychological assessment examining five cognitive domains (memory, visuo-spatial ability, attention/speed of processing, executive function, and language) was administered. A PRS for sleep duration was created based on previously published, genome-wide association study meta-analysis results. In order to assess the relationship between the Sleep PRS and the rate of cognitive change, we used generalized estimating equations analyses. Age, sex, education, ApolipoproteinE-ε4 genotype status, and specific principal components were used as covariates. On a further analysis, sleep medication was used as a further covariate. Results validated the association between Sleep PRS and self-reported sleep duration (B = 1.173, E-6, p = 0.001). Further, in the longitudinal analyses, significant associations were indicated between increased Sleep PRS and decreased visuo-spatial ability trajectories, in both the unadjusted (B = −1305.220, p = 0.018) and the adjusted for the covariates model (B = −1273.59, p = 0.031). Similarly, after adding sleep medication as a covariate (B = −1372.46, p = 0.019), none of the associations between Sleep PRS and the remaining cognitive domains were significant. PRS indicating longer sleep duration was associated with differential rates of cognitive decline over time in a group of non-demented older adults. Common genetic variants may influence the association between sleep duration and healthy aging/cognitive health.

‘Food for Thought’—The Relationship between Diet and Cognition in Breast and Colorectal Cancer Survivors: A Feasibility Study

Survivors of cancer frequently experience persistent and troublesome cognitive changes. Little is known about the role diet and nutrition plays in survivors’ cognition. We explored the feasibility of collecting cross-sectional online data from Australian survivors of breast and colorectal cancer to enable preliminary investigations of the relationships between cognition with fruit and vegetable intake, and the Omega-3 Index (a biomarker of long chain omega 3 fatty acid intake). A total of 76 participants completed online (and postal Omega-3 Index biomarker) data collection (62 breast and 14 colorectal cancer survivors): mean age 57.5 (±10.2) years, mean time since diagnosis 32.6 (±15.6) months. Almost all of the feasibility outcomes were met; however, technical difficulties were reported for online cognitive testing. In hierarchical linear regression models, none of the dietary variables of interest were significant predictors of self-reported or objective cognition. Age, BMI, and length of treatment predicted some of the cognitive outcomes. We demonstrated a viable online/postal data collection method, with participants reporting positive levels of engagement and satisfaction. Fruit, vegetable, and omega-3 intake were not significant predictors of cognition in this sample, however the role of BMI in survivors′ cognitive functioning should be further investigated. Future research could adapt this protocol to longitudinally monitor diet and cognition to assess the impact of diet on subsequent cognitive function, and whether cognitive changes impact dietary habits in survivors of cancer.