Mild Cognitive Impairment Status Research Articles

59 Mild cognitive impairment among older adults with diabetes: A pilot study in San Juan, Puerto Rico

OBJECTIVES/GOALS: Research on mild cognitive impairment (MCI) risk factors in type 2 diabetes mellitus (T2DM) is scarce; however, MCI is a concern in T2DM as it can adversely impact self-care behaviors. This study aims to estimate the proportion of MCI and describe its sociodemographic, clinical, psychosocial, and lifestyle characteristics in older adults with T2DM. METHODS/STUDY POPULATION: Cross-sectional pilot study of 60 adults (aged ≥50yrs) with a diagnosis of T2DM will be recruited at a diabetes center located in San Juan, Puerto Rico. Data on sociodemographic, clinical, psychosocial (depressive symptoms and social support), and lifestyle characteristics related to diabetes self-management (diabetes self-care activities and activities of daily living) will be collected through face-to-face interviews using validated questionnaires. Our primary outcome will be MCI assessed via the Spanish-language version of the Montreal Cognitive Assessment (MoCA-S). The proportion of adults with MCI (MoCA-S score<26) will be estimated, and the sociodemographic, lifestyle, psychosocial, and clinical characteristics of older adults will be compared across MCI status using bivariate analysis. RESULTS/ANTICIPATED RESULTS: Expected results include an estimate of the proportion of MCI among older adults with T2DM, which we hypothesize will be higher in our study than in Puerto Rico’s older adult population (previously reported as 17%). Additionally, we will describe the sociodemographic, clinical, psychosocial, and lifestyle characteristics that significantly differ by MCI status in older adults with T2DM. We expect that those with MCI will be more likely to be females, have lower education and annual income, longer time with a diabetes diagnosis, worse psychosocial profiles (higher levels of depressive symptoms and lower levels of social support), and worse lifestyle profiles (poorer glycemic control and lower activities of daily living score) than those without MCI. DISCUSSION/SIGNIFICANCE: This pilot study is a first step to understanding MCI among older adults with T2DM in Puerto Rico, a Hispanic population with a higher prevalence of T2DM than their US non-Hispanic White counterparts. Its findings can guide the design and implementation of a larger epidemiological study aimed at understanding MCI risk factors among adults with T2DM.

Comparing neuropsychological, typical, and ADNI criteria for the diagnosis of mild cognitive impairment in Vietnam-era veterans.

Neuropsychological criteria for mild cognitive impairment (MCI) more accurately predict progression to Alzheimer's disease (AD) and are more strongly associated with AD biomarkers and neuroimaging profiles than ADNI criteria. However, research to date has been conducted in relatively healthy samples with few comorbidities. Given that history of traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD) are risk factors for AD and common in Veterans, we compared neuropsychological, typical (Petersen/Winblad), and ADNI criteria for MCI in Vietnam-era Veterans with histories of TBI or PTSD. 267 Veterans (mean age = 69.8) from the DOD-ADNI study were evaluated for MCI using neuropsychological, typical, and ADNI criteria. Linear regressions adjusting for age and education assessed associations between MCI status and AD biomarker levels (cerebrospinal fluid [CSF] p-tau181, t-tau, and Aβ42) by diagnostic criteria. Logistic regressions adjusting for age and education assessed the effects of TBI severity and PTSD symptom severity simultaneously on MCI classification by each criteria. Agreement between criteria was poor. Neuropsychological criteria identified more Veterans with MCI than typical or ADNI criteria, and were associated with higher CSF p-tau181 and t-tau. Typical and ADNI criteria were not associated with CSF biomarkers. PTSD symptom severity predicted MCI diagnosis by neuropsychological and ADNI criteria. History of moderate/severe TBI predicted MCI by typical and ADNI criteria. MCI diagnosis using sensitive neuropsychological criteria is more strongly associated with AD biomarkers than conventional diagnostic methods. MCI diagnostics in Veterans would benefit from incorporation of comprehensive neuropsychological methods and consideration of the impact of PTSD.

Comparison of Commonly Measured Plasma and Cerebrospinal Fluid Proteins and Their Significance for the Characterization of Cognitive Impairment Status.

Although cerebrospinal fluid (CSF) amyloid-β42 peptide (Aβ42) and phosphorylated tau (p-tau) and blood p-tau are valuable for differential diagnosis of Alzheimer's disease (AD) from cognitively normal (CN) there is a lack of validated biomarkers for mild cognitive impairment (MCI). This study sought to determine how plasma and CSF protein markers compared in the characterization of MCI and AD status. This cohort study included Alzheimer's Disease Neuroimaging Initiative (ADNI) participants who had baseline levels of 75 proteins measured commonly in plasma and CSF (257 total, 46 CN, 143 MCI, and 68 AD). Logistic regression, least absolute shrinkage and selection operator (LASSO) and Random Forest (RF) methods were used to identify the protein candidates for the disease classification. We observed that six plasma proteins panel (APOE, AMBP, C3, IL16, IGFBP2, APOD) outperformed the seven CSF proteins panel (VEGFA, HGF, PRL, FABP3, FGF4, CD40, RETN) as well as AD markers (CSF p-tau and Aβ42) to distinguish the MCI from AD [area under the curve (AUC) = 0.75 (plasma proteins), AUC = 0.60 (CSF proteins) and AUC = 0.56 (CSF p-tau and Aβ42)]. Also, these six plasma proteins performed better than the CSF proteins and were in line with CSF p-tau and Aβ42 in differentiating CN versus MCI subjects [AUC = 0.89 (plasma proteins), AUC = 0.85 (CSF proteins) and AUC = 0.89 (CSF p-tau and Aβ42)]. These results were adjusted for age, sex, education, and APOEϵ4 genotype. This study suggests that the combination of 6 plasma proteins can serve as an effective marker for differentiating MCI from AD and CN.

GENDER DIFFERENCES IN ASSOCIATIONS OF SLEEP INTRAINDIVIDUAL VARIABILITY AND MILD COGNITIVE IMPAIRMENT

Abstract Previous studies suggest that cognitive function in older adults is related to sleep, with females more vulnerable to poor sleep. Little is known about the relationship between cognition and intraindividual variability of sleep (IIV). We examined the cross-sectional relationship between sleep IIV and mild cognitive impairment (MCI) by gender using data from the Einstein Aging Study. We hypothesize that individuals with MCI have a greater IIV in daily sleep characteristics, and these associations will be stronger for females. Eighty-nine men (age = 76.81±4.73, 61% White, 28% Black, 27% MCI) and 197 women (age = 76.60 ± 4.93, 40% White, 46% Black, 29% MCI) were included in the analysis. Individuals completed 2 weeks of actigraphy (mean ± SD = 15.7 ± 1.1 days), and the Montreal Cognitive Assessment, and MCI was based on the Jack/Bondi criteria. Sleep IIV was estimated as within person standard deviation of nighttime sleep duration, 24-hour sleep duration, wake after sleep onset, and nighttime sleep midpoint. Linear regression models evaluated associations between sleep IIV and MCI status separately by gender, controlling for BMI, age, ethnicity/race, nocturnal hypoxemia, Oxygen Desaturation Index ≥15. Among women, having MCI was associated with greater IIV in nighttime sleep midpoint (b=0.19, p=.002), and in 24-hour total sleep duration (b=13.10, p = .047) with a similar trend in nighttime sleep duration (p = .050). No significant associations were found among men. Findings suggest the importance to keep considering gender in work to understand how sleep variability relates to MCI status in older adults.

THE ROLE OF MILD COGNITIVE IMPAIRMENT AND MARITAL STATUS ON LONELINESS AND INTRUSIVE THOUGHTS IN DAILY LIFE

Abstract Loneliness is associated with maladaptive cognitions (e.g., rumination and intrusive thoughts) among young adults, but less is known about this association among older adults. Experiencing loneliness and intrusive thoughts throughout daily life may disrupt emotion regulation and increase risk for cognitive decline during later life. Moreover, social and cognitive factors, including marital status and mild cognitive impairment (MCI), may be protective or exacerbating factors that moderate these associations. For example, having close relationships (e.g., being married) is associated with better mental health and overall well-being for older adults and intrusive thoughts have been associated with poorer cognitive performance. We used multilevel modeling to examine the association between momentary loneliness and intrusive thoughts among older adults and whether MCI and marital status moderated this association. Participants were 316 diverse older adults without dementia (40% Black; 13% Hispanic, mean age = 77.45 years, 67% women) living in the Bronx, NY who completed ecological momentary assessments 5 times daily for 14 consecutive days. There was a significant three-way interaction (β = -0.175, p < 0.05) such that the association between momentary loneliness and intrusive thoughts was strongest for those with MCI who were not married and weakest for those with MCI who were married. Covariates included race/ethnicity, years of education, age, and gender. These findings suggest that for those who have MCI, being married may be a protective factor against moments of loneliness and intrusive thoughts. For those who are not married, tailoring interventions to accommodate MCI status may be worthwhile.

Within‐Day Variability in Mobile Cognitive Assessments: Associations with Mild Cognitive Impairment and Sociodemographic Factors

AbstractBackgroundGreater within‐person variability in cognitive performance on mobile devices is emerging as a sensitive marker of mild cognitive impairment (MCI). It is unclear if sociodemographic differences are associated with this variability, and if so, whether these differences moderate associations between MCI status and within‐person variability. We use a digital health approach with ecological momentary assessments (EMA) to examine sociodemographic differences in within‐day variability among individuals with MCI and those who were cognitively unimpaired (CU).MethodA sample of 308 community‐dwelling older adults from the Einstein Aging Study (mean age = 77.49 years, SD = 4.86, range = 70‐90; 67% female; 45% non‐Hispanic White, 41% non‐Hispanic Black) completed neuropsychological testing and self‐reported questionnaires. Ninety‐eight individuals met Jak/Bondi criteria for MCI. All participants performed mobile tests of processing speed and memory binding on a smartphone up to six times daily over a two‐week period. We employed heterogeneous variance multilevel models to assess sociodemographic and MCI status associations with within‐day variability across assessments. We further tested whether differences in age, gender, race, and education moderated associations between MCI status and within‐day variability.ResultFor processing speed, greater variability was apparent in individuals with MCI, non‐Hispanic Black participants, and individuals with less education (ps<.001). A MCI status*gender interaction occurred; the association between MCI status and variability remained significant for both genders but was smaller among women (p<.01). For memory binding, greater variability was apparent in individuals with MCI, older participants, non‐Hispanic Black participants, and individuals with less education (ps<.001). Numerous interactions occurred; in separate analyses, associations between MCI status and variability remained significant, but were smaller among women, non‐Hispanic Black participants, and individuals with less education (ps<.05).ConclusionIndividuals with MCI exhibited greater within‐day variability in mobile cognitive performance than those who were CU, but the strength of these associations varied by sociodemographic factors. These indices of variability in everyday life may serve as sensitive markers of early cognitive impairment. Future research should examine daily mechanisms and environmental perturbations (e.g., stress, sleep, air pollution) that may explain why associations between MCI status and cognitive variability appeared smaller among women, non‐Hispanic Black participants, and individuals with less education.

Apathy and dysfunction in Lewy Body Disease

AbstractBackgroundStudies in Alzheimer’s disease and frontal temporal lobe dementia have shown high prevalence and persistence of apathy at different disease stages and its strong association with functional decline. Here we use well‐established methods to examine the relationship between apathy and function in a cohort of well‐characterized patients with Lewy Body Disease (LBD) who had regular assessments over time.MethodSample includes participants in the National Alzheimer’s Coordinating Center Uniform Data Set (NACC‐UDS, 9/2005‐12/2019) who had at baseline (1) cognitive status of mild cognitive impairment (MCI) or dementia, (2) presumed etiologic diagnosis of LBD, and (3) ≥1 follow‐up. Baseline diagnosis of Parkinson’s disease (PD) was assessed. Apathy was identified using clinician judgment. Participants’ function was measured using the Functional Assessment Questionnaire (FAQ). Multivariable linear mixed model (LMM) was used to estimate relationships between apathy, cognitive status (baseline MCI vs dementia), and function over time.ResultThe sample included 339 participants with MCI and 748 with dementia. Average age = 72.7±8.3, 74% male, 86% non‐Hispanic white, 15.4±3.4 years of education, baseline MMSE = 23.7±5.8, with 3.4±1.7 years of follow‐up. Proportion of participants who reported difficulty with function at baseline ranged according to task complexity from 48% (Heating water, making a cup of coffee, turning off stove after use) to 85% (Assembling tax records, business affairs, or papers); with total FAQ = 13.0±9.1. Presence of apathy increased from 52% at baseline to 60% at visit 4. Across all follow‐ups, 24% of the participants were never apathetic, 13.7% had apathy intermittently (<50% of all visits), 28.3% persistently (≥50% of all visits), and 34.0% were apathetic at all visits. LMM estimation results showed that, compared to participants who were never apathetic, FAQ was 3.8±0.8 points higher, i.e., greater dysfunction, at baseline in participants who were always apathetic, and 3.3±0.7 points higher in those who had intermittent/persistent apathy (both p<0.001). Rate of functional decline was 0.41±0.3 points faster each year in those always apathetic compared to never apathetic (p<0.1).ConclusionApathy is highly prevalent in individuals with LBD. Independent of cognitive status, more persistent apathy was strongly associated with worse function.

Associations between Anxious‐Depression and Cognitive Change, Function, and Impairment: Results from the Hispanic Community Healthy Study/Study of Latinos‐Investigations of Neurocognitive Aging

AbstractBackgroundAnxiety and depression often co‐occur and both are risk factors for Alzheimer’s disease and related dementias (ADRD). This study sought to examine associations between anxiety and depressive symptoms with cognitive change, function and impairment among middle‐aged and older Hispanics/Latinos.MethodData included 6,162 middle‐aged and older Hispanic/Latinos adults (Age M = 63.4 years, SD = ±8.2 years; 55% female) enrolled in the Study of Latinos‐Investigation of Neurocognitive Aging study (SOL‐INCA), an ancillary study to the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Participants completed the Spielberger State‐Trait Anxiety Inventory 10‐item (STAI‐10) and Center for Epidemiology Scale for Depression 10‐item (CESD‐10) at HCHS/SOL Visit 1 (2008‐2011). Outcomes of interest include cognitive function at Visit 2, change in cognition from Visit 1 to 2 (approximately 7‐years later in SOL‐INCA), and mild cognitive impairment status (MCI; NIA‐AA diagnostic criteria) at Visit 2. Latent class analysis (LCA) was used to derive phenotypes of anxious‐depression using both STAI‐10 and CESD‐10 items. The phenotypes were used as exposures in survey generalized linear regression models for cognitive function, change, and MCI. Covariables included age, sex, education, income, heritage, center, and antianxiety/antidepressant medication use.ResultLCA results demonstrated 3 classes of anxious‐depression (Low; 62%, Moderate; 30%, and High; 8%). We found consistent negative associations between the Moderate and High group with cognitive function, from baseline. Participants in the High group had more pronounced associations (p<.001) than the Moderate group (p<.01) vs. the Low group, after covariate adjustments. We found consistent negative associations with MCI whereby both Moderate (OR = 1.62, CI = [1.12; 2.33], p<.05) and High (OR = 1.64, CI = [1.25; 2.16], p<.001) groups were associated with higher odds ratios for MCI. However, there were no associations with cognitive change.ConclusionThis study demonstrated the utility of the anxious‐depression construct when investigating the relationships between co‐occurring anxiety and depressive symptoms with cognitive aging among Hispanics/Latinos. Anxious‐depression was negatively associated with cognitive function and MCI status, demonstrating unique effects of co‐occurring anxiety and depressive symptoms among older Hispanic/Latinos. However, further replications are required to evaluate the longitudinal effects of anxious‐depression on cognitive outcomes.

Hippocampal Enlargement and White Matter Hyperintensities in Obstructive Sleep Apnea Patients

AbstractBackgroundObstructive sleep apnea (OSA), which results from recurrent collapses of the upper airway system, affects around 27% of the geriatric population with mild cognitive impairment (MCI) and causes intermittent hypoxia and sleep fragmentation (Mubashir et al., 2019). Prior research suggests that OSA results in brain ischemic preconditioning, causing hippocampal enlargement due to adaptive hippocampal neurogenesis (Rosenzweig et al., 2013). OSA has also been linked to increased white matter hyperintensities (WMHs) through hypoxic‐ ischemic injury, which contribute to cognitive decline in dementias such as Alzheimer’s disease (Zacharias et al., 2021). Previous research necessitates studying the effects of apnea in an elderly population with MCI.MethodIn the Memories2 study, subjects aged 55‐85 underwent a polysomnography and were assigned to the no OSA (OSA‐) group if their apnea‐hypopnea index (AHI) was <5 events/hour or to the OSA (OSA+) group if their AHI was ≥15. Amnestic MCI status was determined with a neuropsychological battery using standard criteria. The subjects received an optional MRI, in which hippocampal and WMH volumetry were derived from a T1‐weighted structural scan and a whole‐brain fluid‐attenuated inversion recovery (FLAIR) scan, respectively. Statistical analyses (two‐sample t‐tests and Wilcoxon‐Mann‐Whitney test) were performed to understand group differences in hippocampal volume and WMH at baseline. Hippocampal volume data (N = 131) was obtained for 67 OSA+ and 64 OSA‐ subjects. WMH data (N = 129) was obtained for 66 OSA+ and 63 OSA‐ subjects.ResultOSA+ subjects had significantly greater right hippocampal volume (p = 0.0374) and left hippocampal volume (0.0336) than the OSA‐ subjects. OSA+ subjects also had higher levels of white matter hyperintensities as compared to the OSA‐ subjects (p = 0.0340) (Table 1).ConclusionIncreased WMH burden is suggestive of hypoxic‐ischemic injury and supports the hypothesis that hippocampal enlargement may be a response to intermittent hypoxia in OSA. These findings reveal the need for early evaluation for sleep apnea. The future direction of this work includes analyzing the group differences adjusting for covariates, detecting and verifying outliers, and rerunning analyses with the complete baseline data. Future data from the Memories2 study will examine the effects of OSA treatment in MCI patients using continuous positive airway pressure (CPAP).

1 Associations of Locus of Control and Memory Self-Awareness in Older Adults with and without MCI

Objective:While loss of insight into one’s cognitive impairment (anosognosia) is a feature in Alzheimer’s disease dementia, less is known about memory self-awareness in cognitively unimpaired (CU) older adults or mild cognitive impairment (MCI) or factors that may impact self-awareness. Locus of control, specifically external locus of control, has been linked to worse cognitive/health outcomes, though little work has examined locus of control as it relates to self-awareness of memory functioning or across cognitive impairment status. Therefore, we examined associations between locus of control and memory self-awareness and whether MCI status impacted these associations.Participants and Methods:Participants from the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) study (mean age=73.51; 76% women; 26% Black/African American) were classified as CU (n=2177) or MCI (amnestic n=313; non-amnestic n=170) using Neuropsychological Criteria. A memory composite score measured objective memory performance and the Memory Functioning Questionnaire measured subjective memory. Memory self-awareness was defined as objective memory minus subjective memory, with positive values indicating overreporting of memory difficulties relative to actual performance (hypernosognosia) and negative values indicating underreporting (hyponosognosia). Internal (i.e., personal skills/attributes dictate life events) and external (i.e., environment/others dictate life events) locus of control scores came from the Personality in Intellectual Aging Contexts Inventory. General linear models, adjusting for age, education, sex/gender, depressive symptoms, general health, and vocabulary examined the effects of internal and external locus of control on memory self-awareness and whether MCI status moderated these associations.Results:Amnestic and non-amnestic MCI participants reported lower internal and higher external locus of control than CU participants. There was a main effect of MCI status on memory self-awareness such that amnestic MCI participants showed the greatest degree of hyponosognosia/underreporting, followed by non-amnestic MCI, and CU participants slightly overreported their memory difficulties. While, on average, participants were fairly accurate at reporting their degree of memory difficulty, internal locus of control was negatively associated with self-awareness such that higher internal locus of control was associated with greater underreporting (ß=-.127, 95% CI [-.164, -.089], p<.001). MCI status did not moderate this association. External locus of control was positively associated with self-awareness such that higher external locus of control was associated with greater hypernosonosia/overreporting (ß=.259, 95% CI [.218, .300], p<.001). Relative to CU, amnestic, but not non-amnestic, MCI showed a stronger association between external locus of control and memory self-awareness. Specifically, higher external locus of control was associated with less underreporting of cognitive difficulties in amnestic MCI (ß=.107, 95% CI [.006, .208], p=.038).Conclusions:In CU participants, higher external locus of control was associated with greater hypernosognosia/overreporting. In amnestic MCI, the lower external locus of control associations with greater underreporting of objective cognitive difficulties suggests that perhaps reduced insight in some people with MCI may result in not realizing the need for external supports, and therefore not asking for help from others. Alternatively, in amnestic participants with greater external locus of control, perhaps the environmental cues/feedback translate to greater accuracy in their memory self-perceptions. Longitudinal analyses are needed to determine how memory self-awareness is related to future cognitive declines.

65 The Impact of PTSD and Mild Cognitive Impairment on Resting State Brain Functional Connectivity in World Trade Center Responders

Objective:Functional connectivity of the default mode network (DMN) during rest has been shown to be different among adults with Mild Cognitive Impairment (MCI) relative to aged-matched individuals without MCI and is predictive of transition to dementia. Post-traumatic stress disorder (PTSD) is also associated with aberrant connectivity of the DMN. Prior work from this group has demonstrated a higher rate of MCI and PTSD among World Trade Center (WTC) responders relative to the general population. The current study sought to investigate the main and interactive effects of MCI and PTSD on DMN functioning. Based on prior work, we hypothesized that MCI, but not PTSD, would predict aberrant connectivity in the DMN.Participants and Methods:99 WTC responders aged 44–65 stratified by MCI status (yes/no) and PTSD status (yes/no) and matched for age in years, sex (male vs. female), race (white, black, and other), and educational attainment (high school or less, some college / technical school, and university degree), and occupation on September 11, 2001 (law enforcement vs. other) underwent fMRI using a 3T Siemens Biograph MR scanner. A single 10-minute continuous functional MR sequence was acquired while participants were at rest with their eyes open. Group-level analyses were conducted using SPM-12, with correction for multiple comparisons using AFNI's 3dClustSim. Based on this threshold, the number of comparisons in our imaging volume, and the smoothness of our imaging data as measured by 3dFWHMx-acf, a minimum cluster size of 1134 voxels was required to have a corrected p . .05 with 2-sided thresholding. Spherical 3 mm seeds were placed in the dorsal (4, -50, 26) and ventral (4, -60, 46) posterior cingulate cortex (PCC).Results:Individuals with PTSD demonstrated significantly less connectivity of the dorsal posterior cingulate cortex (PCC) with medial insula (T = 5.21), subthalamic nucleus (T = 4.66), and postcentral gyrus (T = 3.81). There was no difference found in this study for connectivity between groups stratified by MCI status. There were no significant results for the ventral PCC seed.Conclusions:Contrary to hypotheses that were driven by a study of cortical thickness in WTC responders, the impact of PTSD appears to outweigh the impact of MCI on dorsal DMN connectivity among WTC responders stratified by PTSD and MCI status. This study is limited by several issues, including low number of female and minority participants, relatively small group cell sizes (n = 23–27 per cell), a brief resting state sequence (10 minutes), and lack of a non-WTC control group. Importantly, responders are a unique population so generalizability to other populations may be limited. Individuals in the current study are now being followed longitudinally to relate baseline resting state functional connectivity with cognitive changes and changes in connectivity over a four-year period.

91 Agent Orange Exposure and Mild Cognitive Impairment in U.S. Vietnam Era Veterans

Objective:US forces used Agent Orange (AO) during the Vietnam War and continued to store/test it at other locations after the war. AO is a powerful herbicide including dioxin, a highly toxic ingredient classified as a human carcinogen. The National Academies of Sciences, Engineering, and Medicine periodically review the literature on the health effects of AO exposure (AOE) and concluded in 2018 that there is sufficient evidence linking AO with a wide range of adverse health outcomes, including neurologic disorders (e.g., Parkinson’s disease). The VA has a list of medical disorders considered presumptive conditions related to AOE. More recently, AOE has been linked to a nearly double risk compared to those without AOE for receiving a dementia diagnosis. To our knowledge, no one has investigated the association of AOE to mild cognitive impairment (MCI), a condition thought to precede dementia.Participants and Methods:We examined men in three waves of the Vietnam Era Twin Study of Aging (VETSA). In wave 3, participants self-reported yes/no to the question of whether they ever had prolonged or serious AOE. MCI was diagnosed by the Jak-Bondi approach. Impairment was defined as 2+ tests within a cognitive domain that were more than 1.5 standard deviations below normative means after adjusting for premorbid cognitive ability. In mixed effects models, we tested the effect of AOE on MCI status. Models were adjusted for age, ethnicity, and non-independence within twin pairs.Results:In wave 3, 12.6% (230) of 1167 participants reported AOE. Those with AOE data had mean ages of 51.1 (wave 1), 56.0 (wave 2), and 61.4 (wave 3). Those with data on both AOE and MCI numbered 861 (wave 1), 900 (wave 2), 1121 (wave 3), and 766 had AOE and MCI at all waves. AOE was significantly related to wave 2 MCI (p < .001), but not to waves 1 and 3 MCI. AOE was significantly associated with the number of time points at which someone met criteria for MCI (p = .011). Analyses were conducted on six cognitive domains used to diagnose MCI, using available participants per wave. At all 3 waves, AOE was significantly associated with lower scores in processing speed (p = .003, p = .004, p = .005, respectively), working memory (p < .001, p = .002, p = .008) and nearly significant at all waves for executive dysfunction (p < .001, p < .001, p = .050). There were two other significant associations [wave 2 memory (p = .038), wave 3 fluency (p = .024)]. The semantic fluency cognitive domain was unrelated to AOE in all waves.Conclusions:AOE was consistently associated with lower processing speed, working memory, and executive dysfunction in males ages 51-61. It was also associated with the number of time points at which one met criteria for MCI in that age range, and with MCI in the mid-fifties. Findings support the idea of a risk for greater cognitive decline in those exposed to AO earlier in their lives, and with a risk for developing MCI.

The Association Between Mild Cognitive Impairment and Medication Non-adherence Among Elderly Patients With Chronic Diseases.

Medication adherence is essential for optimizing treatment outcomes in elderly patients who frequently contend with multiple chronic diseases requiring pharmacological interventions. Mild cognitive impairment (MCI) is a prevalent cognitive disorder among the elderly population, but its impact on medication adherence among elderly patients is still uncertain. This cross-sectional study aimed to investigate the impact of MCI on medication adherence among elderly patients. A cross-sectional study of 436 elderly patients with common chronic diseases aged 60 years and above was conducted. Medication adherence was measured using the Morisky Medication Adherence Scale-8 (MMAS-8). MCI was screened, and cognitive status was assessed using the Mini-Mental State Examination (MMSE) questionnaire. Multivariate logistic regression analysis was performed to identify independent risk factors of medication non-adherence. Among these elderly patients, 212 (48.6%) had poor medication compliance, and 181 (41.5%) had MCI. Preliminary analyses showed a significant association between MCI and medication non-adherence among elderly patients (odds ratio (OR)=3.95, 95% confidence interval (95%CI)=2.63-5.92, P<0.001). Multivariate logistic regression analysis showed that MCI was independently associated with the risk of medication non-adherence among elderly patients (adjusted OR=2.64, 95%CI=1.64-4.24, P<0.001). Additionally, adverse drug reaction and poor evaluation of medication effects were also independently associated with medication non-adherence in elderly patients (P<0.05). Findings from this cross-sectional study proved the substantial adverse impact of MCI on medication adherence among elderly patients, and MCI was an independently influential factor of medication non-adherence. Identifying the MCI status early and providing interventions to enhance medication adherence are undoubtedly essential for optimizing healthcare outcomes in elderly patients.

Differences in Life Space Activity Patterns Between Older Adults With Mild Cognitive Impairment Living Alone or as a Couple: Cohort Study Using Passive Activity Sensing.

Measuring function with passive in-home sensors has the advantages of real-world, objective, continuous, and unobtrusive measurement. However, previous studies have focused on 1-person homes only, which limits their generalizability. This study aimed to compare the life space activity patterns of participants living alone with those of participants living as a couple and to compare people with mild cognitive impairment (MCI) with cognitively normal participants in both 1- and 2-person homes. Passive infrared motion sensors and door contact sensors were installed in 1- and 2-person homes with cognitively normal residents or residents with MCI. A home was classified as an MCI home if at least 1 person in the home had MCI. Time out of home (TOOH), independent life space activity (ILSA), and use of the living room, kitchen, bathroom, and bedroom were calculated. Data were analyzed using the following methods: (1) daily averages over 4 weeks, (2) hourly averages (time of day) over 4 weeks, or (3) longitudinal day-to-day changes. In total, 129 homes with people living alone (n=27, 20.9%, MCI and n=102, 79.1%, no-MCI homes) and 52 homes with people living as a couple (n=24, 46.2%, MCI and n=28, 53.8%, no-MCI homes) were included with a mean follow-up of 719 (SD 308) days. Using all 3 analysis methods, we found that 2-person homes showed a shorter TOOH, a longer ILSA, and shorter living room and kitchen use. In MCI homes, ILSA was higher in 2-person homes but lower in 1-person homes. The effects of MCI status on other outcomes were only found when using the hourly averages or longitudinal day-to-day changes over time, and they depended on the household type (alone vs residing as a couple). This study shows that in-home behavior is different when a participant is living alone compared to when they are living as a couple, meaning that the household type should be considered when studying in-home behavior. The effects of MCI status can be detected with in-home sensors, even in 2-person homes, but data should be analyzed on an hour-to-hour basis or longitudinally.

Sleep duration and brain MRI measures: Results from the SOL-INCA MRI study.

Sleep duration has been associated with dementia and stroke. Few studies have evaluated sleep pattern-related outcomes of brain disease in diverse Hispanics/Latinos. The SOL-INCA (Study of Latinos-Investigation of Neurocognitive Aging) magnetic resonance imaging (MRI) study recruited diverse Hispanics/Latinos (35-85 years) who underwent neuroimaging. The main exposure was self-reported sleep duration. Our main outcomes were total and regional brain volumes. The final analytic sample included n=2334 participants. Increased sleep was associated with smaller brain volume (βtotal_brain =-0.05, p<0.01) and consistently so in the 50+ subpopulation even after adjusting for mild cognitive impairment status. Sleeping>9hours was associated with smaller gray (βcombined_gray =-0.17, p<0.05) and occipital matter volumes (βoccipital_gray =-0.18, p<0.05). We found that longer sleep duration was associated with lower total brain and gray matter volume among diverse Hispanics/Latinos across sex and background. These results reinforce the importance of sleep on brain aging in this understudied population. Longer sleep was linked to smaller total brain and gray matter volumes. Longer sleep duration was linked to larger white matter hyperintensities (WMHs) and smaller hippocampal volume in an obstructive sleep apnea (OSA) risk group. These associations were consistent across sex and Hispanic/Latino heritage groups.

Identifying underlying patterns in Alzheimer's disease trajectory: a deep learning approach and Mendelian randomization analysis

Alzheimer's disease (AD) is a heterogeneously progressive neurodegeneration disorder with varied rates of deterioration, either between subjects or within different stages of a certain subject. Estimating the course of AD at early stages has treatment implications. We aimed to analyze disease progression to identify distinct patterns in AD trajectory. We proposed a deep learning model to identify underlying patterns in the trajectory from cognitively normal (CN) to a state of mild cognitive impairment (MCI) to AD dementia, by jointly predicting time-to-conversion and clustering out distinct subgroups characterized by comprehensive features as well as varied progression rates. We designed and validated our model on the ADNI dataset (1370 participants). Prediction of time-to-conversion in AD trajectory was used to validate the expression of the identified patterns. Causality between patterns and time-to-conversion was further inferred using Mendelian randomization (MR) analysis. External validation was performed on the AIBL dataset (233 participants). The proposed model clustered out patterns characterized by significantly different biomarkers and varied progression rates. The discovered patterns also showed a strong prediction ability, as indicated by hazard ratio (CN→MCI, HR=3.51, p<0.001; MCI→AD, HR=8.11, p<0.001), C-Index (CN→MCI, 0.618; MCI→AD, 0.718), and AUC (CN→MCI, 3 years 0.802, 5 years 0.876; MCI→AD, 3 years 0.914, 5 years 0.957). In the external validation cohort, our model demonstrated competitive performance on conversion time prediction (CN→MCI, C-Index=0.693; MCI→AD, C-Index=0.752). Moreover, suggestive associations between CN→MCI/MCI→AD patterns with four/three SNPs were mediated and MR analysis indicated a causal link between MCI→AD patterns and time-to-conversion in the first three years. Our proposed model identifies biologically and clinically meaningful patterns from real-world data and provides promising performance on time-to-conversion prediction in AD trajectory, which could promote the understanding of disease progression, facilitate clinical trial design, and provide potential for decision-making. The National Key Research and Development Program of China, the Key R&D Program of Zhejiang, and the National Nature Science Foundation of China.

Mild Cognitive Impairment is Associated with Poorer Everyday Decision Making.

Older adults are faced with many unique and highly consequential decisions such as those related to finances, healthcare, and everyday functioning (e.g., driving cessation). Given the significant impact of these decisions on independence, wellbeing, and safety, an understanding of how cognitive impairment may impact decision making in older age is important. To examine the impact of mild cognitive impairment (MCI) on responses to a modified version of the Short Portable Assessment of Capacity for Everyday Decision making (SPACED). Participants were community-dwelling, actively driving older adults (N = 301; M age = 77.1 years, SD = 5.1; 69.4% with a college degree or higher; 51.2% female; 95.3% White) enrolled in the Advancing Understanding of Transportation Options (AUTO) study. A generalized linear model adjusted for age, education, sex, randomization group, cognitive assessment method, and study site was used to examine the relationship between MCI status and decision making. MCI status was associated with poorer decision making; participants with MCI missed an average of 2.17 times more points on the SPACED than those without MCI (adjusted mean ratio: 2.17, 95% CI: 1.02, 4.61, p = 0.044). This finding supports the idea that older adults with MCI exhibit poorer decision-making abilities than cognitively normal older adults. It also suggests that older adults with MCI may exhibit poorer decision making across a wide range of decision contexts.

Examining the Bidirectional Nature of Loneliness and Anxiety Among Older Adults in Daily Life.

Loneliness in later life increases the risk for adverse health outcomes; however, less is known about how loneliness is maintained. Anxiety may play an important role in maintaining loneliness, but little is known about how this connection plays out over time in daily life. This study thus focused on the within-person associations between momentary loneliness and anxiety among older adults. Participants were 317 diverse older adults (40% Black; 13% Hispanic, mean age = 77.45 years, 67% women) systematically recruited from the Bronx, NY, who completed ecological momentary assessments 5 times daily for 14 consecutive days. Multilevel models tested bidirectional contemporaneous, momentary cross-lagged (t - 1), day-level cross-lagged (average day to end of day), and day-to-day cross-lagged associations between loneliness and anxiety. Separate sensitivity analyses controlled for concurrent overall mood valence or depressed state. Gender and mild cognitive impairment (MCI) status were tested as moderators at all timescales. Significant bidirectional associations between loneliness and anxiety were found at the contemporaneous and momentary cross-lagged (t - 1) timescales. Higher average daily loneliness predicted higher end-of-day anxiety, but not vice versa. Loneliness and anxiety were not significantly associated from day to day. Sensitivity analyses revealed some associations varied depending on inclusion of either concurrent mood valence or depressed state. Neither gender nor MCI status moderated associations at any timescale. Findings shed light on the complex temporal ordering of loneliness and anxiety in daily life and extend contemporary theoretical notions of loneliness, including the possibility of interventions that target key moments in daily life.

Mild Cognitive Impairment, But Not HIV Status, is Related to Reduced Awareness of Level of Cognitive Performance Among Older Adults

Self-assessment of cognitive abilities can be an important predictor of clinical outcomes. This study examined impairments in self-assessments of cognitive performance, assessed with traditional neuropsychological assessments and novel virtual reality tests among older persons with and without human immunodeficiency virus (HIV) and mild cognitive impairment (MCI). One hundred twenty-two participants (82 persons with HIV; 79 MCI+) completed a traditional neuropsychological battery, DETECT virtual reality cognitive battery, and self-reported their general cognitive complaints, depressive symptoms, and perceptions of DETECT performance. Relationships between DETECT performance and self-assessments of performance were examined as were the correlations between general cognitive complaints and performance. These relations were evaluated across HIV and MCI status, considering the associations of depressive symptoms, performance, and self-assessment. We found no effect of HIV status on objective performance or self-assessment of DETECT performance. However, MCI+ participants performed worse on DETECT and traditional cognitive tests, while also showing a directional bias towards overestimation of their performance. MCI- participants showed a bias toward underestimation. Cognitive complaints were reduced compared to objective performance in MCI+ participants. Correlations between self-reported depressive symptoms and cognitive performance or self-assessment of performance were nonsignificant. MCI+ participants underperformed on neuropsychological testing, while overestimating performance. Interestingly, MCI- participants underestimated performance to approximately the same extent as MCI+ participants overestimated. Practical implications include providing support for persons with MCI regarding awareness of limitations and consideration that self-assessments of cognitive performance may be overestimated. Similarly, supporting older persons without MCI to realistically appraise their abilities may have clinical importance.

Serum microRNA-501-3p is a potential diagnostic tool for detecting mild cognitive impairment: Ehime genome study.

Tight junction disruption and dysfunction are involved in the progression of blood-brain barrier (BBB) breakdown. Recent investigations have revealed BBB disruption in patients with vascular cognitive decline. Our previous studies showed that miR-501-3p negatively regulates cerebral endothelial tight junction protein-1, resulting in the disruption of the BBB, and playing an important role in the development of vascular cognitive impairment. BBB breakdown in white matter lesions is often seen in the patients with vascular mild cognitive impairment (MCI). We therefore hypothesize that most early-phase MCI patients may demonstrate elevated expression of miR-501-3p and sought to investigate whether serum exosome miR-501-3p levels could be a clinical indicator for detecting mild cognitive impairment. One hundred and seventy-eight subjects (aged 73 [68-75] years, 53% male) were recruited for this study. The Japanese version of the Montreal Cognitive Assessment (MoCA-J) was used for detecting MCI. Serum exosome miR-501-3p expression levels were measured by qPCR methods. Patients were divided into two groups depending on whether their miR-501-3p ∆Ct values were above ("High"; n = 74) or below ("Low"; n = 104) cutoff levels determined by ROC curve. MCI was detected significantly more often in the miR-501-3p-High group (vs. -Low group, 63.5% vs. 47.1%, respectively; p < 0.05). Multivariate logistic regression analysis showed a significant association between MCI status and High miR-501-3p (odds ratio 2.662; p < 0.01), improved vs. known risk factors. In non-diabetic patients, High miR-501-3p was positively associated with MCI status (odds ratio 3.633; p < 0.01) and also positively associated with MCI status in those with atherosclerosis (odds ratio 3.219; p < 0.01). The present study demonstrates that elevated expression of blood exosomal miR-501-3p can indicate the presence of MCI in human patients. Early detection of vascular injuries may allow a reduction in progressive dementia through the management of vascular risk factors.