MCI Status Research Articles

The relationship between objective and subjective executive function in Parkinson’s disease

ABSTRACT Introduction Difficulties in executive functioning (EF) are common in PD; however, the relationship between subjective and objective EF is unclear. Understanding this relationship could help guide clinical EF assessment. This study examined the relationship between subjective self-reported EF (SEF) and objective EF (OEF) and predictors of SEF-OEF discrepancies in PD. Method One-hundred and sixteen non-demented PD participants completed measures of OEF (i.e. problem-solving, cognitive flexibility, inhibition, and working memory) and SEF (Frontal Systems Behavior Scale-Self Executive Dysfunction Subscale). Pearson bivariate correlations and linear regressions were performed to examine the relationship between SEF and OEF and the non-motor symptoms (e.g. mood, fatigue), demographic, and PD characteristic (e.g. MCI status) predictors of discrepancies between OEF and SEF (|OEF minus SEF scores|). Correlates of under-, over-, and accurate-reporting were also explored. Results Greater SEF complaints and worse OEF were significantly associated (β =.200, p = .009) and 64% of participants accurately identified their level of OEF abilities. Fewer years of education and greater symptoms of depression, anxiety, and fatigue significantly correlated with greater discrepancies between OEF and SEF. Fatigue was the best predictor of EF discrepancy in the overall sample (β = .281, p = .022). Exploratory analyses revealed apathy and fatigue associated with greater under-reporting, while anxiety associated with greater over-reporting. Conclusions SEF and OEF are significantly related in PD. Approximately 64% of non-demented persons with PD accurately reported their EF skill level, while 28% under-reported and 8% over-reported. SEF-OEF discrepancies were predicted by fatigue in the overall sample. Preliminary evidence suggests reduced apathy and fatigue symptoms relate to more under-reporting, while anxiety relates to greater over-reporting. Given the prevalence of these non-motor symptoms in PD, it is important to carefully consider them when assessing EF in PD.

REVOLUTIONIZING COGNITIVE ASSESSMENT: THE POWER OF DIGITAL BIOMARKERS AND ECOLOGICALLY VALID METHODS

Abstract Digital technologies have allowed neuropsychologists to utilize process-based approaches to assess cognitive function and change. Traditional methods of neuropsychological assessment involve obtaining single scores (often composites) to represent cognitive function. However, modern process-based techniques involve the use of digital data collection to acquire insights into both the manner and reasoning behind an individual’s performance. The present study will share insights into the task development and validation of active and passive digital cognitive assessments from two longitudinal studies of aging: (1) a study of non-dementia participants (N=322), ultra-brief mobile cognitive tests were administered up to six times per day for two weeks; and (2) a neuro-exergaming study (N=31) enrolling patients with MCI and their co-residing study partner, where participants used a study-provided tablet to complete a neuro-exergaming protocol and digital cognitive assessments (e.g., digital trailmaking and eStroop). We analyzed both traditional and process-based metrics in two studies, including mean response time and patterns of inaccuracy. Study one found significant correlations between MCI status and metrics for survey completion time, working memory, and processing speed. Study two found weak to moderate correlations between cognitive function measures from digital and paper-based neuropsychology. Our findings suggest that remote self-administered digital measures can detect subtle cognitive changes. The event-level data, which is collected through a process-based approach, has enormous untapped potential for discovering and confirming novel digital biomarkers of cognitive health and progression that can be monitored beyond clinical settings.

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.

AT(N) Biomarker profiles and Alzheimer’s Disease clinical status and memory in adults with down syndrome

AbstractBackgroundDown syndrome (DS) is seen as a genetic form of Alzheimer’s disease (AD). The National Institute on Aging and the Alzheimer’s Association proposed the AT(N) model for classifying AD biomarkers of amyloid (A), tau (T), and neurodegeneration or neuronal injury ([N]) in non‐DS populations. It is not yet known how the AT(N) classification system maps onto AD pathology and symptomology in DS. The goals of the present study were to: 1) examine AT(N) profiles in DS based on PET amyloid‐beta (Aβ) (A), tau PET (T), and hippocampal volume ([N]); and 2) evaluate potential differences in clinical AD status and memory performance by AT(N) profile in DS.MethodAnalyses included 138 adults with DS (age: M = 39.1, SD = 8.0) enrolled in the Alzheimer’s Biomarker Consortium‐ Down Syndrome study. PET Aβ and tau were assessed using [11C]PiB and [18F]AV‐1451. Structural MRI data was used to index hippocampal volume and adjusted for intracranial volume. Thresholds for elevated (+ vs. ‐) A (Aβ CL >19), T (tau composite SUVr >1.21) and (N) (hippocampal volume < 1 SD from sample mean) were based on prior studies. Clinical AD status (cognitively stable, mild cognitive impairment [MCI‐DS], dementia, and unable to determine) were based on direct measures and caregiver‐report but blind to imaging and biofluid data. The Cued Recall Test was used to assess episodic memory.ResultOverall, 66% of participants were A‐/T‐/(N)‐, 14% were A+/T‐/(N)‐, 9% were A+/T+/(N)‐, and 5% were A+/T+/(N)+. The remaining 6% had an alternative profile (e.g. A‐/T‐/(N)+). One‐way analyses of variance indicated a significant difference in age and clinical AD status by A/T/N profile. General linear models controlling for age and premorbid intellectual disability level indicated differences in memory by A/T/(N) profile.ConclusionThis study adds to the understanding of AT(N) biomarker profiles in DS and their association with AD symptomology. Clinical AD status of MCI‐DS and dementia and worse memory performance were associated with elevated T and (N), in line with non‐DS populations. The unable to determine status paralleled the MCI and dementia status groups. Findings inform models that predict the transition to AD in DS.aging after age 90.

Accelerated cognitive decline and hippocampal volume loss in mild cognitive impaired carriers of Apolipoprotein‐E ε4

AbstractBackgroundThe ε4 allele of the Apolipoprotein‐E (APOE) gene is the major genetic risk factor for late‐onset Alzheimer’s disease (AD). APOE ε4 carriers represent around 45% of AD population, with each copy of APOE ε4 allele conferring increased risk for AD. Here, we aim to quantify disease progression during the early clinical stage of AD using imaging biomarkers to stratify patient populations for therapeutic interventions.MethodsData used in the preparation of this abstract were obtained from the Alzheimer’s Disease Neuroimaging Initiative. CDR some of boxes (CDR‐SB), PET (amyloid load; Florbetapir), MRI (hippocampal volume) and APOE4 genotype were collected. Only MCI patients were included (MMSE=27.6±1.8 and global‐CDR=0.5±0.05). Available follow up data with at least 10 participants were included in the analysis.ResultsData from 1021 participants with baseline MCI status were included in the study (110 ε4 homozygotes, 397 heterozygotes ε4).At baseline, CDR‐SB of non‐carriers and ε4 homozygotes was not different (p=0.24). The annual rate of cognitive decline in ε4 homozygotes (0.7 points per year; p=7e‐8) and heterozygotes ε4 (0.56 points per year; p=4e‐8) was 3.7 to 4.6 times greater than non‐carriers (0.15 points per year; p=0.00005).At baseline, hippocampal volume was significantly (p<0.01) lower in ε4 homozygotes (6.50 mL) and heterozygotes ε4 (6.76 mL) compared to non‐carriers (6.98 mL). The annual rate of hippocampal loss in ε4 homozygotes (0.09 mL; p=0.032) and heterozygotes ε4 (0.13 mL; p=0.0006) was faster than non‐carriers (0.03 mL; p=0.16).At baseline, amyloid load was significantly (p<0.0001) higher in ε4 homozygotes (SUVR=1.37) and heterozygotes ε4 (SUVR=1.31) compared to non‐carriers (SUVR=1.13). The rates of progression were not significantly different across groups.ConclusionAPOE ε4 carriers showed notably greater rate of progression on CDR‐SB compared to non‐carriers. Greater amyloid load and hippocampal atrophy were observed in APOE ε4 carriers compared to non‐carriers at baseline although the CDR‐SB scores were comparable. The amyloid deposition appeared to plateau at MCI. Hippocampal volume loss continued in all groups, with a fastest progression rate in ε4 carriers. Result suggests that detection of therapeutic changes from interventions may be more efficient in this population than the broader population of MCI patients.

Comparing the Emotion Status of Individuals With MCI to Their Cognitively Normal Counterparts: I-CONECT Project

Socially isolated older adults with MCI are at greater risk of developing ADRD. This study compares the emotional status of older adults with MCI to their cognitively normal counterparts within a socially isolated sample. We used baseline data from the Internet-based Conversational Engagement Clinical Trial (NCT02871921). MCI status was determined according to clinical diagnosis. Three emotion domain scores were calculated: negative affect, social satisfaction, and psychological wellbeing. Linear regressions were conducted for all 17 Emotion Battery measures and 3 domain scores. The 127 participants' mean age was 81.1 (SD=4.6). About 54% were diagnosed with MCI. Older adults with MCI had more negative affect, yet no difference was observed in social satisfaction and psychological wellbeing. Individuals with MCI had higher levels of fear, perceived hostility, perceived stress, sadness, and lower self-efficacy. Better understanding the emotional status could inform the development of behavioral health interventions and early detection of MCI.

Aging research in the time of COVID‐19: A telephone screen for subjective cognitive concerns in community‐dwelling ethnically diverse older adults

BackgroundThere is an urgent need for validation of remotely‐administered cognitive screens to identify older adults at risk for dementia, to monitor disease progression, and to facilitate follow‐up when in‐person visits are not feasible. Restrictions on in‐person cognitive assessments due to COVID‐19 have spurred a growing literature on telephone‐based cognitive screening. However, few studies have evaluated the value of telephone‐administered screens of subjective cognitive concerns (SCC), an important early marker of dementia‐risk.MethodEinstein Aging Study participants (subsample, n=455; Mage=77.0; Myears education=15.0; 64.1% women; 46.4% White) completed the Telephone Screen for Subjective Cognitive Concerns (T‐SSCC), a 16‐item measure of self‐reported memory, language, executive functioning, visuospatial/navigation, concentration, calculation, and mental clarity concerns, as well as the Telephone Montreal Cognitive Assessment (T‐MoCA). In‐person assessments included the paper‐and‐pencil Cognitive Change Index (CCI) and comprehensive neuropsychological evaluation. Classification as cognitively normal (CN; n=288) or mild cognitive impairment (MCI; n=153) was based on Jak/Bondi criteria. Primary analyses included correlations between the objective and subjective screening instruments, and logistic regression to evaluate the association between the T‐SSCC and MCI status.ResultTotal endorsement of concerns on the T‐SSCC (OR 1.095, CI 1.018‐1.178, p=0.015) was significantly associated with MCI status. In particular, endorsement of “Do any of these problems interfere with your daily life?” was strongly related to MCI (OR 2.296, CI 1.284‐4.108, p=0.005). The T‐SSCC was moderately correlated with the in‐person CCI (r[114]=0.577, p<0.001). A small but significant relationship was observed between the T‐SSCC and T‐MoCA (r[258]=‐0.206, p<0.001).ConclusionTo our knowledge, this is the first study to validate a telephone SCC screen in response to the crucial need for such remotely administered measures. The T‐SSCC was significantly associated MCI status; furthermore, specific items related to the impact of cognitive problems in daily life were particularly sensitive to MCI. Such SCC measures are brief, accessible, and well‐tolerated and may provide additionally valuable information that enhances remotely‐administered cognitive screens.

Early Microstructure Changes of White Matter Fiber Bundles in Patients with Amnestic Mild Cognitive Impairment Predicts Progression of Mild Cognitive Impairment to Alzheimer's Disease.

Amnestic mild cognitive impairment (aMCI) is the transitional stage between normal aging and Alzheimer's disease (AD). Some aMCI patients will progress into AD eventually, whereas others will not. If the trajectory of aMCI can be predicted, it would enable early diagnosis and early therapy of AD. To explore the development trajectory of aMCI patients, we used diffusion tensor imaging to analyze the white matter microstructure changes of patients with different trajectories of aMCI. We included three groups of subjects:1) aMCI patients who convert to AD (MCI-P); 2) aMCI patients who remain in MCI status (MCI-S); 3) normal controls (NC). We analyzed the fractional anisotropy and mean diffusion rate of brain regions, and we adopted logistic binomial regression model to predicate the development trajectory of aMCI. The fraction anisotropy value is significantly reduced, the mean diffusivity value is significantly increased in the two aMCI patient groups, and the MCI-P patients presented greater changes. Significant changes are mainly located in the cingulum, fornix, hippocampus, and uncinate fasciculus. These changed brain regions significantly correlated with the patient's Mini-Mental State Examination scores. The study predicted the disease trajectory of different types of aMCI patients based on the characteristic values of the above-mentioned brain regions. The prediction accuracy rate can reach 90.2%, and the microstructure characteristics of the right cingulate band and the right hippocampus may have potential clinical application value to predict the disease trajectory.

Mandibular bone changes and dental status: A radiomorphometric study by the mandibular cortical index on a Senegalese female population aged 40 years and over

IntroductionA panoramic radiography is a test, which allows the evaluation of the maxillo-mandibular anatomy. The objective of this study was to use panoramic radiography to evaluate the state of the mandibular basilar cortical of normal tooth and edentulous female subjects over 40 years of age by the mandibular cortical index. Research methods and materialsThis was a cross-sectional study of female subjects aged 40 years and over. A sample size of 360 radiographs of 180 totally edentulous and 180 normal tooth subjects were considered for this study. The mandibular basilar cortical bone was assessed by the mandibular cortical index using the classification described by Klemetti: C1 (normal cortex), C2 (slightly or moderately eroded cortex), C3 (severely eroded cortical layer). Statistical data collection and analysis were conducted with Jamovi. The results for qualitative variables were expressed in percentages and those of quantitative variables in means ± standard deviation. The significance level was set at p ≤ 0.05. ResultsThe average age for normal tooth subjects was 55 ± 11 years. Subjects with C1 CMI represented 27.8% of the population studied, 55.3%, and 16.9% for C2 and C3 indices respectively. The association between MCI and dental status revealed a significant statistical difference p < 0.05. Edentulism is a predictive factor of basilar cortical status after results analysis of polynomial logistic regression ConclusionThis study shows that age combined with dental status are factors affecting the mandibular bone changes investigated by the MCI.

Mild Cognitive Impairment and Donepezil Impact Mitochondrial Respiratory Capacity in Skeletal Muscle.

Alzheimer's Disease (ad) associates with insulin resistance and low aerobic capacity, suggestive of impaired skeletal muscle mitochondrial function. However, this has not been directly measured in AD. This study ( n = 50) compared muscle mitochondrial respiratory function and gene expression profiling in cognitively healthy older adults (CH; n = 24) to 26 individuals in the earliest phase of ad-related cognitive decline, mild cognitive impairment (MCI; n = 11) or MCI taking the ad medication donepezil (MCI + med; n = 15). Mitochondrial respiratory kinetics were measured in permeabilized muscle fibers from muscle biopsies of the vastus lateralis. Untreated MCI exhibited lower lipid-stimulated skeletal muscle mitochondrial respiration (State 3, ADP-stimulated) than both CH ( P = .043) and MCI + med (P = .007) groups. MCI also exhibited poorer mitochondrial coupling control compared to CH (P = .014). RNA sequencing of skeletal muscle revealed unique differences in mitochondrial function and metabolism genes based on both MCI status (CH vs MCI) and medication treatment (MCI vs MCI + med). MCI + med modified over 600 skeletal muscle genes compared to MCI suggesting donepezil powerfully impacts the transcriptional profile of muscle. Overall, skeletal muscle mitochondrial respiration is altered in untreated MCI but normalized in donepezil-treated MCI participants while leak control is impaired regardless of medication status. These results provide evidence that mitochondrial changes occur in the early stages of AD, but are influenced by a common ad medicine. Further study of mitochondrial bioenergetics and the influence of transcriptional regulation in early ad is warranted.

Lifestyle Complexity and Dementia Risk: Examining Moderation by APOE Genotype and Mild Cognitive Impairment

Prior studies suggest that the neuroprotective effect of physical exercise is moderated by APOE genotype and MCI status, but it remains unclear whether this extends to lifestyle complexity defined by a broader variety of physical, intellectual, and social activities. Participants were from the Ginkgo Evaluation of Memory (GEM) Study. We used 18 physical, intellectual, or social activities from the Lifestyle Activity Questionnaire. We performed latent class analysis to characterize subgroups with distinct activity response patterns and examined whether they have differential risk of incident dementia over time. A three-class model was chosen based on fit statistics and interpretability. Cox proportional hazards models, adjusted for potential demographic and health confounders, revealed that Class 1 (Highly intellectually/socially active) had a reduced risk of dementia compared to Class 3 (Less socially/less intellectually active; HR=.71, 95% CI: [.56,.88], p=.002). Class 2 (Socially/less intellectually active) did not differ in risk from Class 3 (HR=.90, 95% CI: [.73,1.1], p=.288). There was no evidence for effect modification for APOE e4 allele carriers (p’s>.05), but the protective association for Class 1 only held for those without prevalent MCI at baseline (HR=.74, 95% CI: [.56,.98], p=.033). Results showed that subgroups characterized by a greater variety of social and intellectual activities had reduced risk for dementia, but only for those without MCI. This implies that late-life lifestyle complexity may be most neuroprotective for those in the preclinical stages of decline. Results also suggested that lifestyle complexity may act through a cognitive reserve pathway unrelated to amyloid pathology.

Actigraphic Measures of Sleep Quality Associated With Ambulatory Cognitive Performance in Older Adults

Few longitudinal studies link objectively assessed sleep and cognitive performance in ecologically-valid environments. Participants enrolled in the community-based Einstein Aging Study cohort (n=224, M[age]=77.17). Wake after sleep onset (WASO) was associated with worse cognitive performance with and without MCI (2-week smartphone-based EMA, six assessments/day). Models include age, gender, ethnicity, education, learning effects, sleep duration, WASO*MCI interaction (p=0.015 for Symbol Match; p=0.002 for Color Shape). Associations were stronger among those with MCI, thirty minutes more nightly WASO predicted a 500ms longer Symbol Match response time (p<0.0001), 5.05% higher Color Dot error proportion (p=0.002), 0.184 points lower Color Shape accuracy (p<0.0001). In those without MCI, WASO was associated with worse cognition: thirty minutes more nightly WASO predicted +166.7ms Symbol Match response time (p=0.03) and -0.06 points Color Shape accuracy (p=0.013). Actigraphic sleep quality associated with ambulatory cognitive performance (and worse with MCI status) suggests targets for prevention/mitigation of cognitive decline. Part of a symposium sponsored by the Sleep, Circadian Rhythms and Aging Interest Group.

Midlife Plasma Aβ and Late-Life Risk of Cognitive Impairment: The Atherosclerosis Risk in Communities Study

Plasma-based biomarkers of amyloid beta (Aβ), a neuropathological hallmark of Alzheimer’s disease, show promise in predicting cognitive impairment and mapping onto cerebral amyloidosis, but little is known about how midlife plasma Aβ associates with late-life cognitive outcomes. Midlife plasma variants Aβ42 and Aβ40 were measured using a fluorimetric bead-based immunoassay in a subsample of visit 3 ARIC participants (1993-95; n=2585, mean age=59.4±5.2, 57% female, 23% African American). We investigated the relationship between midlife plasma Aβ and late-life mild cognitive impairment (MCI; n=923) and dementia (n=628) diagnosed from 2011-19. Multinomial logistic regressions estimated relative risk ratios (RRR) of MCI, dementia, and death vs normal cognitive status as a function of:(1) Aβ42:Aβ40 ratio, (2) Aβ42 and Aβ40 included as separate terms, and (3) Protected Aβ group (participants with Aβ42≥46 pg/ml and Aβ40 <233 pg/ml). Adjusters included age, sex, education, site-race, and APOE4. Every doubling of midlife plasma Aβ42:Aβ40 up to a threshold of 0.20 was associated with 41% lower risk of developing MCI/dementia in comparison to cognitively normal (RRR=0.59 [95% CI:0.42, 0.82]), with no association for ratio values ≥0.20. Every standard deviation increase in plasma Aβ42 was associated with 17% lower risk of dementia (RRR=0.83 [0.70, 0.99]), whereas every standard deviation increase in plasma Aβ40 was associated with 16% higher risk of MCI (RRR=1.16 [1.02, 1.31]). The protected midlife plasma Aβ group had 86% lower risk of late-life dementia vs all others (RRR=0.14 [0.04, 0.47]). Early measurement of plasma Aβ may prove an accessible and effective population screener for future cognitive impairment.

1146 Interaction Of Mild Cognitive Impairment And Late-life Depression In Actigraphy And Self Report Of Sleep Problems

Abstract Introduction Late-life depression has been proposed as a precursor to amnestic Mild Cognitive Impairment (aMCI), the prodrome of Alzheimer’s disease. Both conditions are associated with sleep and cognitive problems. We hypothesized that MCI and current depressive symptoms would co-occur more frequently, but express distinct sleep phenotypes. Methods Independently living older adults (N=80), age 62-90 (M=71.78, SD=5.98), were recruited from a geriatric psychiatry clinic and the community for a home sleep study. A clinical decision board and neurocognitive battery were used to determine MCI status. Participants completed the CES-D and depression history interview where endorsement of current depression was considered positive. Sleep was examined with wrist actigraphy for 7 days. Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), Stanford Sleepiness Scale (SSS) provided subjective sleep quality. Results Based on these criteria, 41.2% of the sample were determined to be MCI (n=33); the remainder were deemed normative for age (NC; n=47). Chi-square analyses showed a higher frequency of MCI were positive for current depression than expected (14.2%; p=0.017). Repeated-measures MANOVA, using current depression symptoms and MCI as factors, revealed MCI was associated with longer sleep latency (p=0.035) and wake bout time (p=0.039); whereas, current depression was associated with longer sleep latency, more fragmentation/WASO, and lower sleep efficiency (p’s&amp;lt;0.05), self-report of poorer daytime dysfunction (p=0.005), and greater daytime sleepiness (p=0.001). MCI x current depression interactions were found for sleep latency (p=0.029); and PSQI sleep disturbances (p=0.005) and sleep medication (p=0.025). Conclusion Despite distinct sleep disordered phenotypes, the interaction of MCI and current depression is associated with delayed sleep onset, use sleep medication and report of sleep disturbances. Support This project was sponsored by: NASA, Maine Space Consortium; AG 056176, AG 053164 Vice President for Research, U. Maine; Maine Technology Institute; DoD Phase I SBIR and R44AG059536-01 SBIR Phase II Award.

Late-Onset Epilepsy With Unknown Etiology: A Pilot Study on Neuropsychological Profile, Cerebrospinal Fluid Biomarkers, and Quantitative EEG Characteristics.

Introduction: Despite the fact that epilepsy has been associated with cognitive decline, neuropsychological, neurobiological, and neurophysiological features in patients with late-onset epilepsy of unknown etiology (LOEU) are still unknown. This cross-sectional study aims to investigate the neuropsychological profile, cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD), and resting-state quantitative electroencephalographic (qEEG) cortical rhythms in LOEU patients with mild cognitive impairment (LOEU-MCI) and with normal cognition (LOEU-CN), compared to non-epileptic MCI (NE-MCI) and cognitively normal (CN) controls.Methods: Consecutive patients in two clinical Units diagnosed with LOEU-CN (19), LOEU-MCI (27), and NE-MCI (21) were enrolled, and compared to age and sex-matched cognitively normal subjects CN (11). Patients underwent standardized comprehensive neuropsychological evaluation and CSF core AD biomarkers assessment (i.e., CSF Aβ42, phospho-tau and total tau, classified through A/T/(N) system). Recordings of resting-state eyes-closed electroencephalographic (EEG) rhythms were collected and cortical source estimation of delta (<4 Hz) to gamma (>30 Hz) bands with exact Low Resolution Electromagnetic Tomography (eLORETA) was performed.Results: Most LOEU patients had an MCI status at seizure onset (59%). Patients with LOEU-MCI performed significantly worse on measures of global cognition, visuo-spatial abilities, and executive functions compared to NE-MCI patients (p < 0.05). Regarding MCI subtypes, multiple-domain MCI was 3-fold more frequent in LOEU-MCI than in NE-MCI patients (OR 3.14, 95%CI 0.93–10.58, p = 0.06). CSF Aβ42 levels were lower in the LOEU-MCI compared with the LOEU-CN group. Finally, parietal and occipital sources of alpha (8–12 Hz) rhythms were less active in the LOEU-MCI than in the NE-MCI and CN groups, while the opposite was true for frontal and temporal cortical delta sources.Discussion: MCI status was relatively frequent in LOEU patients, involved multiple cognitive domains, and might have been driven by amyloidosis according to CSF biomarkers. LOEU-MCI status was associated with abnormalities in cortical sources of EEG rhythms related to quiet vigilance. Future longitudinal studies should cross-validate our findings and test the predictive value of CSF and EEG variables.

Connectivity Between Brain Networks Dynamically Reflects Cognitive Status of Parkinson’s Disease: A Longitudinal Study

Background:Cognitive impairment in Parkinson’s disease (PD) is associated with altered connectivity of the resting state networks (RSNs). Longitudinal studies in well cognitively characterized PD subgroups are missing.Objectives:To assess changes of the whole-brain connectivity and between-network connectivity (BNC) of large-scale functional networks related to cognition in well characterized PD patients using a longitudinal study design and various analytical methods.Methods:We explored the whole-brain connectivity and BNC of the frontoparietal control network (FPCN) and the default mode, dorsal attention, and visual networks in PD with normal cognition (PD-NC, n = 17) and mild cognitive impairment (PD-MCI, n = 22) as compared to 51 healthy controls (HC). We applied regions of interest-based, partial least squares, and graph theory based network analyses. The differences among groups were analyzed at baseline and at the one-year follow-up visit (37 HC, 23 PD all).Results:The BNC of the FPCN and other RSNs was reduced, and the whole-brain analysis revealed increased characteristic path length and decreased average node strength, clustering coefficient, and global efficiency in PD-NC compared to HC. Values of all measures in PD-MCI were between that of HC and PD-NC. After one year, the BNC was further increased in the PD-all group; no changes were detected in HC. No cognitive domain z-scores deteriorated in either group.Conclusion:As compared to HC, PD-NC patients display a less efficient transfer of information globally and reduced BNC of the visual and frontoparietal control network. The BNC increases with time and MCI status, reflecting compensatory efforts.

Motoric Cognitive Risk Syndrome: Could It Be Defined Through Increased Five-Times-Sit-to-Stand Test Time, Rather Than Slow Walking Speed?

Background: Slow walking speed, time to perform the five-times-sit-to-stand (FTSS) test and motoric cognitive risk syndrome (MCR; defined as slow gait speed combined with subjective cognitive complaint) have been separately used to screen older individuals at risk of cognitive decline. This study seeks to (1) compare the characteristics of older individuals with MCR, as defined through slow walking speed and/or increased FTSS time; and (2) examine the relationship between MCR and its motor components as well as amnestic (a-MCI) and non-amnestic (na-MCI) Mild Cognitive Impairment.Methods: A total of 633, individuals free of dementia, were selected from the cross-sectional “Gait and Alzheimer Interactions Tracking” study. Slow gait speed and increased FTSS time were used as criteria for the definition of MCR. Participants were separated into five groups, according to MCR status: MCR as defined by (1) slow gait speed exclusively (MCRs); (2) increased FTSS time exclusively (MCRf); (3) slow gait speed and increased FTSS time (MCRsaf); (4) MCR; irrespective of the mobility test used (MCRsof); and (5) the absence of MCR. Cognitive status (i.e., a-MCI, na-MCI, cognitively healthy) was also determined.Results: The prevalence of MCRs was higher, when compared to the prevalence of MCRf (12.0% versus 6.2% with P ≤ 0.001). There existed infrequent overlap (2.4%) between individuals exhibiting MCRs and MCRf, and frequent overlap between individuals exhibiting MCRs and na-MCI (up to 50%). a-MCI and na-MCI were negatively [odd ratios (OR) ≤ 0.17 with P ≤ 0.019] and positively (OR ≥ 2.41 with P ≤ 0.019) related to MCRs, respectively.Conclusion: Individuals with MCRf are distinct from those with MCRs. MCRf status does not relate to MCI status in the same way that MCRs does. MCRs is related negatively to a-MCI and positively to na-MCI. These results suggest that FTTS cannot be used to define MCR when the goal is to predict the risk of cognitive decline, such as future dementia.

Structural Correlates of Personality Dimensions in Healthy Aging and MCI.

The revised NEO Personality Inventory (NEOPI-R), popularly known as the five-factor model, defines five personality factors: Neuroticism, Extraversion, Openness to Experience, Agreeableness, and Conscientiousness. The structural correlates of these personality factors are still a matter of debate. In this work, we examine the impact of subtle cognitive deficits on structural substrates of personality in the elderly using DTI derived white matter (WM) integrity measure, Fractional Anisotropy (FA). We employed canonical correlation analysis (CCA) to study the relationship between personality factors of the NEOPI-R and FA measures in two population groups: healthy controls and MCI. Agreeableness was the only personality factor to be associated with FA patterns in both groups. Openness was significantly related to FA data in the MCI group and the inverse was true for Conscientiousness. Furthermore, we generated saliency maps using bootstrapping strategy which revealed a larger number of positive correlations in healthy aging in contrast to the MCI status. The MCI group was found to be associated with a predominance of negative correlations indicating that higher Agreeableness and Openness scores were mostly related to lower FA values in interhemispheric and cortico-spinal tracts and a limited number of higher FA values in cortico-cortical and cortico-subcortical connection. Altogether these findings support the idea that WM microstructure may represent a valid correlate of personality dimensions and also indicate that the presence of early cognitive deficits led to substantial changes in the associations between WM integrity and personality factors.

Cross-Sectional Relationships of Physical Activity and Sedentary Behavior With Cognitive Function in Older Adults With Probable Mild Cognitive Impairment.

Mild cognitive impairment (MCI) represents a transition between normal cognitive aging and dementia and may represent a critical time frame for promoting cognitive health through behavioral strategies. Current evidence suggests that physical activity (PA) and sedentary behavior are important for cognition. However, it is unclear whether there are differences in PA and sedentary behavior between people with probable MCI and people without MCI or whether the relationships of PA and sedentary behavior with cognitive function differ by MCI status. The aims of this study were to examine differences in PA and sedentary behavior between people with probable MCI and people without MCI and whether associations of PA and sedentary behavior with cognitive function differed by MCI status. This was a cross-sectional study. Physical activity and sedentary behavior in adults dwelling in the community (N = 151; at least 55 years old) were measured using a wrist-worn actigraphy unit. The Montreal Cognitive Assessment was used to categorize participants with probable MCI (scores of <26/30) and participants without MCI (scores of ≥26/30). Cognitive function was indexed using the Alzheimer Disease Assessment Scale-Cognitive-Plus (ADAS-Cog Plus). Physical activity and sedentary behavior were compared based on probable MCI status, and relationships of ADAS-Cog Plus with PA and sedentary behavior were examined by probable MCI status. Participants with probable MCI (n = 82) had lower PA and higher sedentary behavior than participants without MCI (n = 69). Higher PA and lower sedentary behavior were associated with better ADAS-Cog Plus performance in participants without MCI (β = -.022 and β = .012, respectively) but not in participants with probable MCI (β < .001 for both). This study was cross-sectional and therefore could not establish whether conversion to MCI attenuated the relationships of PA and sedentary behavior with cognitive function. The diagnosis of MCI was not confirmed with a physician; therefore, this study could not conclude how many of the participants categorized as having probable MCI would actually have been diagnosed with MCI by a physician. Participants with probable MCI were less active and more sedentary. The relationships of these behaviors with cognitive function differed by MCI status; associations were found only in participants without MCI.

Oxidative stress, inflammation and mild cognitive impairment

IntroductionOxidative stress (OS) and inflammation are processes known to be implicated in neurodegeneration. Moreover, risk factors for dementia (depression, obesity, sedentary lifestyle, diabetes, etc.) are associated with up-regulation of pro-inflammatory cytokines. OS has been found in animal models to contribute to cerebral amyloid angiopathy. However, investigations of the associations between OS, inflammation and MCI, typically in small clinical samples have produced mixed results.ObjectivesClarify associations, between OS, inflammation and MCI in a large cohort of community-living individuals.MethodsCognitively healthy individuals (n = 211, 44% female, 75.2 years) and with MCI (n = 23, 44% female, 75.2 years) from a population sample were included. MCI diagnosis was established based on a detailed neuropsychological assessment. Inflammatory (IL1b, IL4, IL6, IL8, IL10, TNF-a) and OS (total anti-oxidants, NO, neopterin) markers were assessed in plasma samples. Associations between biomarkers, MMSE, and MCI status were tested with multiple linear and logistic regression analyses.ResultsUnivariate analyses showed that log IL4 (estimate: −0.175, SE: 0.085, P = 0.041) and NO (estimate: 0.015, SE: 0.006, P = 0.017) were the only markers associated with MMSE scores. MCI status was predicted by log IL4 (estimate: 0.822, SE: 0.357, P = 0.021) and total anti-oxidants (estimate: −0.007, SE: 0.003, P = 0.014). Controlling for pro-inflammatory conditions (T2D, BMI, depression, hypertension) removed the associations with inflammation but not with OS.ConclusionsThese results indicate that increased systemic inflammation and increased OS were associated with lower MMSE scores and higher odds of having MCI. This confirms that systemic pro-inflammatory processes are associated with impaired cognition and should be specifically considered in treatment and risk-reduction interventions.Disclosure of interestThe authors have not supplied their declaration of competing interest.