Clinical Cognitive Status Research Articles

Association between Cerebrospinal Fluid sTREM2 Levels and Depression: The Alzheimer's Disease Neuroimaging Initiative Study.

Previous studies demonstrated a significant protective effect of elevated cerebrospinal fluid (CSF) sTREM2 levels on brain structure and cognitive decline. Nonetheless, the role of sTREM2 in the depression progression remains unclear. This study aimed to investigate the association between CSF sTREM2 levels and longitudinal trajectories of depression. Data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) Study were used. CSF sTREM2 levels and depression were measured using an ELISA-based assay and the Geriatric Depression Scale (GDS-15), respectively. Linear mixed-effect models were employed to assess the relationships between CSF sTREM2 levels and GDS scores. A total of 1,017 participants were enrolled at baseline, with a mean follow-up time of 4.65 years. Baseline CSF sTREM2 levels were negatively correlated with GDS scores (β=-0.21, P=0.022) after adjustment for age, gender, race/ethnicity, education, APOE ε4 carrier status, TREM2 rare variant carrier status, marital status, smoking, and clinical cognitive status. Our findings suggested that a higher level of CSF sTREM2 was associated with a lower risk of depression.

Theory of mind in mild cognitive impairment and Parkinson’s disease: The role of memory impairment

BackgroundSocial cognition is impaired in Parkinson’s disease (PD). Whether social cognitive impairment (iSC) is a by-product of the underlying cognitive deficits in PD or a process independent of cognitive status is unknown. To this end, the present study was designed to investigate the weight of specific cognitive deficits in social cognition, considering different mild cognitive impairment subtypes of PD (PD-MCI).MethodsFifty-eight PD patients underwent a neuropsychological battery assessing executive functions, memory, language, and visuospatial domains, together with social cognitive tests focused on theory of mind (ToM). Patients were divided into subgroups according to their clinical cognitive status: amnestic PD-MCI (PD-aMCI, n = 18), non-amnestic PD-MCI (PD-naMCI, n = 16), and cognitively unimpaired (PD-CU, n = 24). Composite scores for cognitive and social domains were computed to perform mediation analyses.ResultsMemory and language impairments mediated the effect of executive functioning in social cognitive deficits in PD patients. Dividing by MCI subgroups, iSC occurred more frequently in PD-aMCI (77.8%) than in PD-naMCI (18.8%) and PD-CU (8.3%). Moreover, PD-aMCI performed worse than PD-CU in all social cognitive measures, whereas PD-naMCI performed worse than PD-CU in only one subtype of the affective and cognitive ToM tests.ConclusionsOur findings suggest that ToM impairment in PD can be explained by memory dysfunction that mediates executive control. ToM downsides in the amnesic forms of PD-MCI may suggest that subtle changes in social cognition could partly explain future transitions into dementia. Hence, the evaluation of social cognition in PD is critical to characterize a possible behavioral marker of cognitive decline.

Brain Microstructural Changes in Patients with Amnestic mild Cognitive Impairment : Detected by Neurite Orientation Dispersion and Density Imaging (NODDI) Combined with Machine Learning.

This study investigated brain microstructural changes in patients with amnestic mild cognitive impairment (aMCI) by retrospectively analyzing neurite orientation dispersion and density imaging (NODDI) data with machine learning algorithms. A total of 26 aMCI patients and 24 healthy controls (HC) underwent NODDI magnetic resonance imaging (MRI) examinations. The NODDI parameters including neurite density index (NDI), orientation dispersion index (ODI), and volume fraction of isotropic water molecules (Viso) were estimated. Machine learning algorithms such as K‑nearest neighbor (KNN), logistic regression (LR), random forest (RF), and support vector machine (SVM) were used to evaluate the diagnostic efficacy of NODDI parameters in predicting aMCI. The differences in the NODDI parameter values between the aMCI and HC groups were analyzed using the independent sample t‑test, False discovery rate (FDR) correction was used for multiple testing. After adjusting for age, sex, and educational years, partial correlation analysis was used to evaluate the relationship between NODDI parameters and clinical cognitive status of aMCI patients. The NDI, ODI, and Viso values of white matter (WM) and gray matter (GM) structure templates combined with the KNN, LR, RF and SVM machine learning algorithms accomplished the discrimination between aMCI and HC groups. The NDI and ODI values decreased (pvalue range, < 0.001-0.042) and Viso values increased (pvalue range, < 0.001-0.043) in the aMCI group compared to the HCs. The NDI, ODI, and Viso values of the WM and GM structure templates with significant differences were significantly correlated with mini-mental state examination (MMSE) and Montreal cognitive assessment (MoCA) scores. NODDI combined with machine learning algorithms is apromising strategy for early diagnosis of aMCI. Moreover, NODDI parameters correlated with the clinical cognitive status of aMCI patients.

Olfactory dysfunction is associated with mild cognitive impairment in community-dwelling older adults.

BackgroundOlfactory impairment is aging related and is associated with cognitive decline in older adults. However, it remains unclear if an olfactory impairment is associated with mild cognitive impairment (MCI) and the degree of impairment in the MCI subtypes.Materials and methodsIn a cohort of community-living older adults aged 60 years and above, 670 participants were recruited from the Community Health and Intergenerational (CHI) Study. Olfactory function was assessed using a locally developed nine-item smell test in association with neurocognitive assessments. Analysis of covariance (ANCOVA) was used to examine the association of smell identification score and clinical cognitive status while considering demographic, clinical, and neuropsychological factors with Bonferroni correction for group comparisons.ResultsAge-related smell detection between normal aging (NA) and MCI participants had no significant difference. The overall mean smell identification score in older adults was negatively correlated with age. The mean smell identification score of MCI participants was also not significantly different as compared with NA, but an amnestic MCI multiple domain (aMCI_MD) subgroup had significantly lower (impaired) mean smell identification scores compared with the NA and MCI single domain (amnestic and non-amnestic) group.ConclusionThis study demonstrated that olfactory identification impairment is a comorbidity in older adults with amnestic MCI (aMCI) and is a potential marker associated with an early stage of a neurocognitive disorder. The smell test could act as a screening tool to help in the early detection of smell impairment for heterogeneous syndromes of MCI among community-dwelling older adults. Clinicians and researchers could benefit from utilizing the locally developed smell test to screen their patients or research participants before the initiation of an appropriate health intervention or in a clinical trial.

0636 Objective sleep as a predictor of cognitive decline among non-demented elderly: preliminary results from the Cretan Aging Cohort

Abstract Introduction Sleep disturbances have been linked with cognitive decline and previous cross-sectional have shown that long sleep duration is a marker of disease severity in patients Mild Cognitive Impairment (MCI) and Dementia.Our aim was to examine the longitudinal associations between sleep quantity and quality indices and cognitive progression in non-demented community-dwelling elderly. Methods A sub-sample of 62 participants (72.6% females) were recruited from a large population-based cohort in the island of Crete, Greece of 3,140 older adults (&amp;gt;60yrs). Participants were followed-up 8 years later (phase III). All participants underwent neuropsychiatric/neuropsychological evaluation (phases II &amp; III) and a 3-day 24h actigraphy (phase II).Participants were diagnosed as CNI(N=38) and MCI(N=24) during phase II, and CNI (N=22), MCI (N=27) and Dementia (N=13) during phase III. On follow-up, 28 participants progressed to a cognitively declined diagnosis compared to phase II (deteriorated group), while 34 did not (non-deteriorated group). Objective sleep variables at phase II were compared between the deteriotated/non-deteriorated groups using ANCOVA controlling for confounders. Also, differences in neuropsychological testing scores (phase II- phase III) were calculated and associations of differences with sleep variables were examined using partial correlation models controlling for confounders. Results The deteriorated group compared to non-deteriorated had significantly longer night total sleep time (TST) (442±72.6min vs. 407±53.6min, p=0.033), 24h-TST (484±8.9min vs. 434±66.4min, p=0.008), night time in bed (TMB) (537±78.7min vs. 497±62.7min, p=0.03), and 24h-TMB (603±85min vs. 539±85min, p=0.005). Episodic memory worsening was moderately correlated with night TST (r=.316), night and 24h-TMB (r=.526, and r= .442 respectively), wake time after sleep onset (r=.351), and average duration of night awakenings (r=.405). Immediate episodic memory recall decline was positively correlated with night TMB (r=.338). Conclusion Preliminary results from the Cretan aging cohort indicate that almost half of the participants deteriorated cognitively in 8 years and this decline was predicted by objective sleep duration at baseline. Long sleep at baseline may predict deterioration of clinical cognitive status in non-demented elderly at follow-up. It appears that prolonged objective sleep duration and time in bed are novel and clinically useful prognostic factors of cognitive deterioration in elderly with or without cognitive deficits. Support (If Any) National Strategic Reference Framework (NSRF) - Research Funding Program: THALES entitled “UOC-Multidisciplinary network for the study of Alzheimer’s Disease” Grant Cod: MIS 377299HELLENIC FOUNDATION FOR REASEARCH AND INNOVATION (HFRI)- Research Funding Program: ELIDEK entitled “Sleep Apnea (OSA) and poor sleep as Risk Factors for decreased cognitive performance in patients with Mild Cognitive Impairment: the Cretan Aging Cohort (CAC)”, Grant Cod: HFR1-FM17-4397

Plasma biomarker profiles and the association with cognitive function across the clinical spectrum of Alzheimer's disease

AbstractBackgroundThe plasma biomarkers showed a promising value in the disease management of Alzheimer’s disease (AD). However, the profiles of the plasma biomarkers and the association with cognitive domains along the spectrum of AD have seldom been reported.MethodA total of 451 participants were recruited from a memory clinic cohort and a cohort with community‐dwellings. The global and domain‐specific neuropsychological tests were administrated in all participants. The Clinical Dementia Rating (CDR) was used to assess the severity of cognitive impairment. The diagnosis of mild cognitive impairment (MCI) and dementia were based on the Petersen’s criteria and DSM‐IV criteria. The AD was diagnosed according to the NINCDS‐ADRDA criteria. We described the continuum of AD based on the combination of CDR and the cognitive diagnosis: NC (CDR = 0), aMCI‐s (CDR = 0.5), aMCI‐m (CDR = 0.5), AD (CDR = 1), AD (CDR = 2), and AD (CDR = 3). The plasma Aβ 40, Aβ 42, Aβ 42/Aβ 40, t‐Tau, neurofilament protein light chain, and p‐Tau 181 were quantified using the Single molecule array platform. One‐way Analysis of Variance and Welch test were used for comparison among plasma markers. The association between domain z scores and log‐transformed plasma biomarker indexes were examined using partial Pearson correlation analysis with the adjustment for confounding variables.ResultThe concentration of plasma p‐Tau 181 basically increased along the clinical cognitive status, from normal cognition (CDR = 0) to AD (CDR = 3). There are varying degrees of correlation between six plasma biomarkers and different cognitive domains. Plasma p‐Tau 181 had the strongest correlation with MMSE (r = ‐0.494, P&lt; 0.001), Memory (r = ‐0.417, P&lt; 0.001), Attention (r = ‐0.388, P&lt; 0.001), Visuospatial function (r = ‐0.328, P&lt; 0.001), and Language (r = ‐0.123, P= 0.014). There was significant negative correlation between plasma p‐Tau 181 and four subgroups of cognitive domains, including MMSE in CDR &gt;=1 group, Memory in CDR = 0.5 group &amp; CDR &gt;=1 group, and Attention in CDR &gt;= 1 group.ConclusionPlasma p‐Tau 181 increased along the clinical continuum of AD, and had the strongest correlation with cognitive domains among all plasma biomarkers.

Application of 18F-AV45 PET imaging in subtle cognitive decline and mild cognitive impairment patients

Objective To investigate the correlations between cerebral β-amyloid (Aβ) deposition assessed by 18F-florbetapir (AV45) PET imaging and clinical cognitive symptoms in patients with subtle cognitive decline (SCD) and mild cognitive impairment (MCI). Methods Data of twenty-four patients (11 males, 13 females, age: (63.2±7.6) years) diagnosed as SCD (n=15) or MCI (n=9) from December 2018 to March 2019 in Shanghai Jiao Tong University Affiliated Sixth People′s Hospital were collected prospectively. All patients underwent 18F-AV45 PET imaging, brain MRI T1 scan and Mini-Mental State Examination (MMSE) within two weeks. 18F-AV45 PET images were analyzed visually (positive, mild positive, negative). After being pretreated according to the MRI, 18F-AV45 PET images were analyzed semi-quantitatively by calculating the standardized uptake value ratio (SUVR) of Aβ deposition in 8 regions of interest (ROIs; frontal lobe, lateral parietal lobe, lateral temporal lobe, medial temporal lobe, occipital lobe, basal ganglia, posterior cingulate and precuneus), with cerebellar gray matter as the reference. Partial correlation coefficients between regional SUVRs and MMSE score were calculated. Results 18F-AV45 PET imaging showed that 16 patients with positive results and 8 patients with mild positive results. MMSE score of 24 patients was 28.2±2.0, and the SUVR was 0.93-1.87. Correlation analysis revealed that Aβ deposition in frontal cortex (r=-0.432), posterior cingulate lobe (r=-0.434) and precuneus (r=-0.418) was negatively correlated with MMSE score (all P 0.05). Conclusion 18F-AV45 PET imaging can noninvasively detect brain Aβ deposition in patients, and can effectively reflect the clinical cognitive status of patients with SCD and MCI to a certain extent. Key words: Cognition disorders; Amyloid; Positron-emission tomography

Subjective Cognitive Decline Prediction of Mortality: Results from the Einstein Aging Study.

The relation of pre-dementia stages to mortality has not been fully explored. Previous work examining subjective cognitive decline (SCD) and mortality is limited and mixed regarding methods used and consistency of findings. To examine SCD and mortality in a longitudinal, community-based cohort, using item response theory (IRT) methodology to form a composite SCD measure. Also, to assess whether this relationship was independent of clinical cognitive status. The Einstein Aging Study is a diverse longitudinal cohort of adults aged ≥70. SCD items were extracted from baseline CERAD questionnaires and a composite score was formed using IRT methodology. A total of 1,741 participants with complete data were clinically diagnosed as cognitively normal, or as having amnestic mild cognitive impairment (aMCI), nonamnestic mild cognitive impairment (naMCI), or dementia. 645 deaths occurred over a period of 8,912 person-years of follow-up. Cox proportional hazard models predicted time to death adjusting for covariates. A one standard deviation unit increase in level of SCD was associated with >20% higher risk of mortality. However, when models were adjusted for clinical cognitive status, the association was no longer significant. Both dementia and aMCI predicted mortality. Furthermore, when analyses focused only on those without cognitive impairment, SCD level did not predict mortality. The association of SCD with mortality may be due to the association of SCD with clinical cognitive status. Thus, SCD may be used as a community-based screen to initially identify those with cognitive impairment who may be at greatest risk for death.

SOCIAL NETWORKS AND COGNITIVE PERFORMANCE IN OLDER ADULTS WITH NORMAL COGNITION, MILD COGNITIVE IMPAIRMENT, AND MILD ALZHEIMER’S DISEASE

An emerging area of research points to an inverse association between social integration and risk for dementia. However, social integration measures in this literature are limited. The current study uses an egocentric network design wherein detailed data are collected on the specific individuals to whom subjects are connected, and on ties between them. The Social Networks in AD (SNAD) protocol was designed to examine associations between social network dynamics (size, density, composition, strength, supportiveness) and disease-associated factors. We administered SNAD to 82 cognitively normal (CN), 23 mild cognitive impairment (MCI), and 16 Alzheimer's disease (AD) subjects from the Indiana Alzheimer's Disease Center. Bivariate statistics were used to identify significant associations. Network characteristics varied significantly across diagnostic groups (df=2; Table 1 and Figure 1). CN individuals reported networks that were larger (p<.05) and less densely-connected (p<.01) than those with MCI or AD, and networks that contained affectively weaker ties (p<.01) and proportionally more friends versus kin (p<.05). Moreover, correlations revealed positive associations of global cognitive performance (MoCA) with network size (r=0.31; p<.001) and with proportion of friends (r=0.23; p<.001). MoCA performance was negatively correlated with network density (r=-0.23; p<.01) and mean tie strength (r=-0.30; p<.001). We observed similar patterns in all cognitive domains except visuospatial. Verbal memory (Craft Story Delayed Recall) was associated with larger (r=0.27; p<.01), less dense (r=-0.20; p<.05), and weaker networks (r=-0.21; p<.05). Executive function (Trail Making Test B) was more impaired in those with smaller networks (r=0.24; p<.01). Finally, subjects with larger networks (r=0.20; p<.05) composed of weaker ties (r=-0.22; p<.05) performed better on an attention task (Digit Span Test). We found more homogenous, insular, and kin-centered networks in MCI and AD relative to CN. Access to social resources through networks may create conditions that are protective of cognitive decline. Alternatively, our data may support a social contraction mechanism, wherein weaker ties to non-kin decay in the context of cognitive decline. Typical core network structure, function*, and composition by clinical cognitive status. *Note: Strength of tie denoted by thickness of black circle.

Influence of Studies Published by the Journal of the American Geriatrics Society: Top 20 Articles from 2000-2015.

Influence of Studies Published by the Journal of the American Geriatrics Society: Top 20 Articles from 2000-2015.

Physical activity and risk of cognitive impairment among oldest-old women.

Physical activity may reduce the risk of cognitive decline in the elderly, but its effects among the oldest-old (i.e., those aged 85 years and older) are not well known. Our study assessed the association between very late-life physical activity and 5-year risk of mild cognitive impairment (MCI) or dementia and neuropsychological test performance among oldest-old women. This prospective study was conducted at three sites. Participants included 1,249 women (mean [standard deviation] age: 83.3 [2.8] years). Baseline physical activity was measured by self-reported blocks walked per week and analyzed according to tertile. Five years later, surviving participants who were 85 years and older (oldest-old) completed neuropsychological testing and underwent adjudication of clinical cognitive status (normal, MCI, or dementia). All analyses were adjusted for baseline age, education, cognition, depression, body mass index, hypertension, smoking, and coronary artery disease. Compared with women in the lowest tertile, women in the highest tertile were less likely to develop dementia (13.0% versus 23.2%; multivariate adjusted odds ratio: 0.54 [95% confidence interval: 0.36-0.82]). However, risk of MCI was not associated with physical activity. Physical activity was also associated with higher performance 5 years later on tests of global cognition, category fluency, and executive function but not phonemic fluency, memory, or attention. Higher level of very late-life physical activity was associated with a lower risk of subsequent dementia in oldest-old women. These findings support future studies for late-life physical activity interventions for the prevention of dementia among oldest-old women.

Depressive Symptoms in Oldest-Old Women: Risk of Mild Cognitive Impairment and Dementia

Increasing evidence suggests that depression is a risk factor for cognitive impairment, but it is unclear if this is true among the oldest old. We determined whether elevated depressive symptoms predicted 5-year incident mild cognitive impairment (MCI) or dementia, and neuropsychological test performance among oldest-old women. Prospective. Three study sites. 302 women ≥85 years (mean, 87 ± 2). Depressive symptoms were measured with the 15-item Geriatric Depression Scale (GDS); scores of 6 or more indicated elevated symptoms. Five years later, participants completed neuropsychological testing and clinical cognitive status was adjudicated. In analyses of MCI versus normal cognition, 70% of women with GDS score 6 or more at baseline developed MCI versus 37% with GDS score less than 6. After adjustment for age, education, alcohol, and benzodiazepine use, and study site, GDS score 6 or more remained independently associated with much greater likelihood of developing MCI (multivariable odds ratio [MOR] = 3.71, 95% confidence interval (CI): 1.30-10.59). In analyses of dementia versus normal cognition, 65% of women with GDS score 6 or more developed dementia compared with 37% of those with GDS score less than 6 (MOR = 3.15, 95% CI: 1.03-9.65). Only 19% of women with GDS score 6 or more had normal cognitive status 5 years later, compared with 46% of those with GDS score less than 6 (MOR = 0.28, 95% CI: 0.11-0.73). Women with elevated depressive symptoms had worse scores on tests of global cognition and working memory. Elevated depressive symptoms are an important risk factor for cognitive disorders and lower cognitive performance among women living to their ninth and tenth decades.

Antiretroviral Monocyte Efficacy Score Linked to Cognitive Impairment in Hiv

Monocytes transmigrating to the brain play a central role in HIV neuropathology. We hypothesized that the continued existence of neurocognitive impairment (NCI) despite potent antiretroviral (ARV) therapy is mediated by the inability of such therapy to control this monocyte/macrophage reservoir. Cross-sectional and longitudinal analyses were conducted within a prospectively enrolled cohort. We devised a monocyte efficacy (ME) score based on the anticipated effectiveness of ARV medications against monocytes/macrophages using published macrophage in vitro drug efficacy data. We examined, within an HIV neurocognitive database, its association with composite neuropsychological test scores (NPZ8) and clinical cognitive diagnoses among subjects on stable ARV medications unchanged for >6 months prior to assessment. Among 139 subjects on ARV therapy, higher ME score correlated with better NPZ8 performance (r=0.23, P<0.01), whereas a score devised to quantify expected penetration effectiveness of ARVs into the brain (CPE score) did not (r=0.12, P=0.15). In an adjusted model (adjusted r(2)=0.12), ME score (β=0.003, P=0.02), CD4(+) T-cell nadir (β=0.001, P<0.01) and gender (β=-0.456, P=0.02) were associated with NPZ8, whereas CPE score was not (β=0.003, P=0.94). A higher ME score was associated with better clinical cognitive status (P<0.01). With a range of 12.5-433.0 units, a 100-unit increase in ME score resulted in a 10.6-fold decrease in the odds of a dementia diagnosis compared with normal cognition (P=0.01). ARV efficacy against monocytes/macrophages correlates with cognitive function in HIV-infected individuals on ARV therapy within this cohort. If validated, efficacy against monocytes/macrophages may provide a new target to improve HIV NCI.

Circadian activity rhythms and risk of incident dementia and mild cognitive impairment in older women

Previous cross-sectional studies have observed alterations in activity rhythms in dementia patients but the direction of causation is unclear. We determined whether circadian activity rhythms measured in community-dwelling older women are prospectively associated with incident dementia or mild cognitive impairment (MCI). Activity rhythm data were collected from 1,282 healthy community-dwelling women from the Study of Osteoporotic Fractures (SOF) cohort (mean age 83 years) with wrist actigraphy for a minimum of three 24-hour periods. Each participant completed a neuropsychological test battery and had clinical cognitive status (dementia, MCI, normal) adjudicated by an expert panel approximately 5 years later. All analyses were adjusted for demographics, body mass index (BMI), functional status, depression, medications, alcohol, caffeine, smoking, health status, and comorbidities. After 4.9 years of follow-up, 195 (15%) women had developed dementia and 302 (24%) had developed MCI. Older women with decreased activity rhythms had a higher likelihood of developing dementia or MCI when comparing those in the lowest quartiles of amplitude (odds ratio [OR] = 1.57; 95% CI, 1.09-2.25) or rhythm robustness (OR = 1.57; 95% CI, 1.10-2.26) to women in the highest quartiles. An increased risk of dementia or MCI (OR = 1.83; 95% CI, 1.29-2.61) was found for women whose timing of peak activity occurred later in the day (after 3:51 PM) when compared to those with average timing (1:34 PM-3:51 PM). Older, healthy women with decreased circadian activity rhythm amplitude and robustness, and delayed rhythms have increased odds of developing dementia and MCI. If confirmed, future studies should examine whether interventions (physical activity, bright light exposure) that influence activity rhythms will reduce the risk of cognitive deterioration in the elderly.