Function In Mild Cognitive Impairment Research Articles

Unlocking Optimal Strategies: A Systematic Review Exploring the Efficacy of Physical Exercise vs Cognitive Training for Enhancing Executive Functions in Mild Cognitive Impairment and Dementia

Unlocking Optimal Strategies: A Systematic Review Exploring the Efficacy of Physical Exercise vs Cognitive Training for Enhancing Executive Functions in Mild Cognitive Impairment and Dementia

The role of cognitive flexibility on higher level executive functions in mild cognitive impairment and healthy older adults

BackgroundMild Cognitive Impairment (MCI) is a preclinical condition between healthy and pathological aging, which is characterized by impairments in executive functions (EFs), including cognitive flexibility. According to Diamond’s model, cognitive flexibility is a core executive function, along with working memory and inhibition, but it requires the development of these last EFs to reach its full potential. In this model, planning and fluid intelligence are considered higher-level EFs. Given their central role in enabling individuals to adapt their daily life behavior efficiently, the goal is to gain valuable insight into the functionality of cognitive flexibility in a preclinical form of cognitive decline. This study aims to investigate the role of cognitive flexibility and its components, set-shifting and switching, in MCI. The hypotheses are as follows: (I) healthy participants are expected to perform better than those with MCI on cognitive flexibility and higher-level EFs tasks, taking into account the mediating role of global cognitive functioning; (II) cognitive flexibility can predict performance on higher-level EFs (i.e., planning and fluid intelligence) tasks differently in healthy individuals and those diagnosed with MCI.MethodsNinety participants were selected and divided into a healthy control group (N = 45; mean age 64.1 ± 6.80; 66.6% female) and an MCI group (N = 45; mean age 65.2 ± 8.14; 40% female). Cognitive flexibility, fluid intelligence, planning, and global cognitive functioning of all participants were assessed using standardized tasks.ResultsResults indicated that individuals with MCI showed greater impairment in global cognitive functioning and EFs performance. Furthermore, the study confirms the predictive role of cognitive flexibility for higher EFs in individuals with MCI and only partially in healthy older adults.

Moderating effect of education on glymphatic function and cognitive performance in mild cognitive impairment.

This research aims to investigate putative mechanisms between glymphatic activity and cognition in mild cognitive impairment (MCI) and analyzes whether the relationship between cognitive reserve (CR) and cognition was mediated by glymphatic activity. 54 MCI patients and 31 NCs were enrolled to evaluate the bilateral diffusivity along the perivascular spaces and to acquire an index for diffusivity along the perivascular space (ALPS-index) on diffusion tensor imaging (DTI). The year of education was used as a proxy for CR. The ALPS-index was compared between two groups and correlation analyses among the ALPS-index, cognitive function, and CR were conducted. Mediation analyses were applied to investigate the correlations among CR, glymphatic activity and cognition. MCI group had a significantly lower right ALPS-index and whole brain ALPS-index, but higher bilateral diffusivity along the y-axis in projection fiber area (Dyproj) than NCs. In MCI group, the left Dyproj was negatively related to cognitive test scores and CR, the whole brain ALPS-index was positively correlated with cognitive test scores and CR. Mediation analysis demonstrated that glymphatic activity partially mediated the correlations between CR and cognitive function. MCI exhibited decreased glymphatic activity compared to NCs. CR has a protective effect against cognitive decline in MCI, and this effect may be partially mediated by changes in glymphatic activity.

Comparative Efficacy, Tolerability, and Acceptability of Donanemab, Lecanemab, Aducanumab, Melatonin, and Aerobic Exercise for a Short Time on Cognitive Function in Mild Cognitive Impairment and Mild Alzheimer's Disease: A Systematic Review and Network Meta-Analysis.

The Food and Drug Administration (FDA) has approved lecanemab and aducanumab and is reviewing donanemab, but they have questionable efficacy, serious side effects and are costly, whereas melatonin administration and aerobic exercise for a short time may overcome these problems. We aim to compare the efficacy on cognitive function, tolerability and acceptability of melatonin administration and aerobic exercise for a short time with donanemab, lecanemab, and aducanumab in people with mild AD and MCI. We systematically reviewed relevant randomized placebo-controlled trials (RCTs) in PubMed, the Cochrane Library, CINHAL, and ClinicalTrials.gov and performed network meta-analyses. The analysis included 10 randomized placebo-controlled trials with 4,599 patients. Although melatonin and aerobic exercise for a short time were significantly more effective than donanemab, lecanemab, aducanumab and placebo in the primary analysis, there was significant heterogeneity. In the sensitivity analysis excluding exercise, melatonin was significantly more effective than donanemab, lecanemab, aducanumab and placebo, with no significant heterogeneity. Aerobic exercise for a short time was significantly less acceptable than donanemab, aducanumab and placebo. Donanemab, lecanemab, and aducanumab were significantly less tolerable than placebo and donanemab and lecanemab were significantly less acceptable than placebo. Melatonin may be a better potential disease-modifying treatment for cognitive decline in mild AD and MCI. Aerobic exercise for a short time might also be better than donanemab, lecanemab and aducanumab if continued, as it is well tolerated and more effective, although less valid due to heterogeneity. Another limitation is the small number of participants.

Cognitive, Emotional, and Daily Functioning Domains Involved in Decision-Making among Patients with Mild Cognitive Impairment: A Systematic Review.

Mild cognitive impairment (MCI) is a transitional or prodromal stage of dementia in which autonomies are largely preserved (autonomies are not particularly affected). However, this condition may entail a depletion of decision-making (DM) abilities likely due to a gradual deterioration of the prefrontal cortex and subcortical brain areas underlying cognitive-emotional processing. Given the clinical implications of a decline in self-determination observed in some MCI sufferers, the present systematic review was aimed at investigating the literature addressing DM processes in patients with MCI, consistent with PRISMA guidelines. The six online databases inquired yielded 1689 research articles that were screened and then assessed based on eligibility and quality criteria. As a result, 41 studies were included and classified following the PICOS framework. Overall, patients with MCI who underwent neuropsychological assessment were found to be slightly or moderately impaired in DM abilities related to financial management, medical adherence, specific cognitive performances, risky conditions, and especially uncertain life circumstances. Comparative cross-sectional studies indicated not only mid-stage cognitive functioning in MCI but also borderline or deficit DM patterns evaluated through different tasks and procedures. Further research addressing MCI profiles suggested an association between explicit memory, executive functions, and DM performance. These findings highlight the diversity of MCI manifestations, in addition to the critical importance of DM features and correlates in patients' daily functioning. Due to a lack of consensus on both MCI and DM, this review paper sought to shed light on assessment and intervention strategies accounting for the interplay between emotion, motivation, and learning to foster DM in cognitively impaired individuals.

Validation of the Japanese version of the Social Functioning in Dementia scale and COVID-19 pandemic's impact on social function in mild cognitive impairment and mild dementia.

We aimed to psychometrically evaluate and validate a Japanese version of the Social Functioning in Dementia scale (SF-DEM-J) and investigate changes in social function in people with dementia during the coronavirus disease-19 (COVID-19) pandemic. We interviewed people with mild cognitive impairment (MCI) and mild dementia and their caregivers during June 2020-March 2021 to validate patient- and caregiver-rated SF-DEM-J and compared their scores at baseline (April 2020 to May 2020) and at 6-8 months (January 2021 to March 2021) during a time of tighter COVID-19 restrictions. The neuropsychology clinic in the Department of Psychiatry at Osaka University Hospital and outpatient clinic in the Department of Psychiatry and Neurology at Daini Osaka Police Hospital, Japan. 103 dyads of patients and caregivers. SF-DEM-J, Mini-Mental State Examination, Neuropsychiatric Inventory, UCLA Loneliness Scale, and Apathy Evaluation Scale. The scale's interrater reliability was excellent and test-retest reliability was substantial. Content validity was confirmed for the caregiver-rated SF-DEM-J, and convergent validity was moderate. Caregiver-rated SF-DEM-J was associated with apathy, irritability, loneliness, and cognitive impairment. The total score of caregiver-rated SF-DEM-J and the score of Section 2, "communication with others," significantly improved at 6-8 months of follow-up. The SF-DEM-J is acceptable as a measure of social function in MCI and mild dementia. Our results show that the social functioning of people with dementia, especially communicating with others, improved during the COVID-19 pandemic, probably as a result of adaptation to the restrictive life.

Exploring the impact of intensified multiple session tDCS over the left DLPFC on brain function in MCI: a randomized control trial

Transcranial direct current stimulation combined with cognitive training (tDCS-cog) represents a promising approach to combat cognitive decline among healthy older adults and patients with mild cognitive impairment (MCI). In this 5-day-long double-blinded randomized trial, we investigated the impact of intensified tDCS-cog protocol involving two trains of stimulation per day on working memory (WM) enhancement in 35 amnestic and multidomain amnestic MCI patients. Specifically, we focused to improve WM tasks relying on top-down attentional control and hypothesized that intensified tDCS would enhance performance of visual object matching task (VOMT) immediately after the stimulation regimen and at a 1-month follow-up. Secondarily, we explored whether the stimulation would augment online visual working memory training. Using fMRI, we aimed to elucidate the neural mechanisms underlying the intervention effects by analyzing BOLD activations during VOMT. Our main finding revealed no superior after-effects of tDCS-cog over the sham on VOMT among individuals with MCI as indicated by insignificant immediate and long-lasting after-effects. Additionally, the tDCS-cog did not enhance online training as predicted. The fMRI analysis revealed brain activity alterations in right insula that may be linked to tDCS-cog intervention. In the study we discuss the insignificant behavioral results in the context of the current evidence in tDCS parameter space and opening the discussion of possible interference between trained cognitive tasks.

Quantitative EEG Spectral and Connectivity Analysis for Cognitive Decline in Amnestic Mild Cognitive Impairment.

Mild cognitive impairment (MCI) is considered to be the borderline of cognitive changes associated with aging and very early dementia. Cognitive functions in MCI can improve, remain stable or progress to clinically probable AD. Quantitative electroencephalography (qEEG) can become a useful tool for using the analytical techniques to quantify EEG patterns indicating cognitive impairment. The aim of our study was to assess spectral and connectivity analysis of the EEG resting state activity in amnestic MCI (aMCI) patients in comparison with healthy control group (CogN). 30 aMCI patients and 23 CogN group, matched by age and education, underwent equal neuropsychological assessment and EEG recording, according to the same protocol. qEEG spectral analysis revealed decrease of global relative beta band power and increase of global relative theta and delta power in aMCI patients. Whereas, decreased coherence in centroparietal right area considered to be an early qEEG biomarker of functional disconnection of the brain network in aMCI patients. In conclusion, the demonstrated changes in qEEG, especially, the coherence patterns are specific biomarkers of cognitive impairment in aMCI. Therefore, qEEG measurements appears to be a useful tool that complements neuropsychological diagnostics, assessing the risk of progression and provides a basis for possible interventions designed to improve cognitive functions or even inhibit the progression of the disease.

Chanwuyi Lifestyle Medicine Program Improves Memory and Executive Functions of Older Adults With Mild Cognitive Impairment.

The Chanwuyi Lifestyle Medicine Program (CLMP) was found to enhance the memory and executive functions of older adults with or without subjective memory complaints. The present study investigated whether similar beneficial effects can be extended to mild cognitive impairment (MCI). Twenty-four older adults with MCI were randomly assigned to receive the CLMP (the experimental group) or strategic memory training (SMT; the active control group) for 10 weeks. They were assessed by neuropsychological tests at baseline and post-intervention. Older adults showed similar visual and verbal memory improvements after receiving the CLMP and SMT. Yet, only those who received the CLMP showed distinct improvements in planning/organization, working memory, and attention in terms of accuracy, with greater cognitive gains associated with older age and lower levels of education and baseline cognitive functions. This study provides preliminary evidence for the effects of the CLMP on improving memory, attention, and executive functions in MCI.

Cognitive Function After Stopping Folic Acid and DHA Intervention: An Extended Follow-Up Results from the Randomized, Double Blind, Placebo-Controlled Trial in Older Adults with Mild Cognitive Impairment.

Our previously randomized controlled trial (RCT) showed daily oral folic acid (FA), docosahexaenoic acid (DHA) and their combined treatment for 6 months could significantly improve cognitive function in mild cognitive impairment (MCI) individuals. This study aimed to evaluate whether this benefit seen in the treatment group would sustain after stopping intervention when patients returned to a real-world. RCT (ChiCTR-IOR-16008351) was conducted in Tianjin, China. 160 MCI elders aged ≥60 years were randomly divided into four groups: FA + DHA, FA, DHA, and control. 138 MCI elders who completed the 6-month interventional trial underwent another 6-month follow-up without receiving nutritional therapy. Cognitive performance was measured at 6 and 12 months. Blood amyloid-β peptide (Aβ) and homocysteine (Hcy) related biomarkers were measured at baseline and 6 months. In comparison to the end of nutritional therapy, all intervention groups had considerably lower full-scale IQ, arithmetic, and image completion scores during the follow-up period, while the combined intervention and DHA groups had significantly lower picture arrangement scores. Furthermore, after 6-month treatment with FA and FA + DHA, plasma Aβ40, Aβ42, and Hcy levels were significantly decreased. However, these biomarker levels at the start of follow-up were positively correlated with the degree of cognitive function change during follow-up period. FA and DHA supplementation enhance cognitive performance in MCI elderly following a six-month intervention by reducing Hcy or Aβ levels. However, their effects on improving cognitive decline are likely to diminish when the intervention is discontinued.

Discrepancies Between Informant vs. Patient Ratings of Functional Abilities: Association with Objective Cognitive Performance in Mild Cognitive Impairment and mild dementia

AbstractBackgroundSelf‐ and informant‐ratings of functional abilities are used to diagnose mild cognitive impairment (MCI) versus dementia and are a common outcome measure in clinical trials. These ratings are assumed to be accurate, yet they are subject to biases. Biases in patient ratings of daily function have been found in individuals with dementia who are older and more depressed (Martyr et al., 2012, 2019, 2022). Biases in informant ratings have been found in caregivers with higher distress and burden (Mangone et al., 1993; Martyr et al., 2014, 2022) and higher education (Hackett et al., 2020). The current study examined discrepancies in informants’ ratings of daily functioning in individuals with MCI/mild dementia.MethodParticipants were 118 patients clinically diagnosed with MCI or mild dementia and their care partners/informants who were referred to the Emory Cognitive Empowerment Program. Table 1 shows details regarding all measured constructs and variables. The discrepancy between informant rating of daily function and patients’ cognition (i.e., informant daily function rating and patient cognition discrepancy) and the informant‐ and patient discrepancy in ratings of daily function (i.e., informant/patient daily function rating discrepancy) served as dependent variables. Two forward linear regression models were run.ResultTable 2 shows demographic information. For the informant daily function rating and patient cognition discrepancy, informants with higher perceived stress reported worse patient functioning. For the informant/patient daily function discrepancy score, worse ratings of daily function by the informant than the patient were found for informants with higher caregiver burden, worse communicative effectiveness, and patients with higher self‐efficacy.ConclusionThis study highlights the potential for biases in patient and informant ratings of functional abilities in MCI/mild dementia. The risk for underreporting functional abilities in informants with higher burden and stress levels and lower communicative effectiveness aligns with previous research indicating that ratings can be biased by individual factors. Worse ratings by informants than patients for patients with higher self‐efficacy may also be due to individual factors in patients such as presence of anosognosia. These findings have implications for the use of perceived functional ratings for diagnostic purposes and as outcome measures in clinical trials.

P185: Comparison of social function in mild cognitive impairment and mild dementia using the Japanese version of the Social Functioning in Dementia scale (SF-DEM-J)

Objective:The present study aimed to compare the social function between mild cognitive impairment (MCI), mild Alzheimer’s disease (AD) dementia, and mild dementia with Lewy bodies (DLB) using the Japanese version of Social Functioning in Dementia scale (SF-DEM-J).Methods:We interviewed 103 patients and family caregivers from June 2020 to March 2021: 54 patients with MCI, 34 with mild AD dementia, and 15 with mild DLB. We compared the caregiver-rated SF-DEM-J, Clinical Dementia Rating (CDR), MMSE, age, length of education, Geriatric Depression Scale (GDS), the University of California, Los Angeles Loneliness Scale (UCLA-LS), Neuropsychiatric Inventory (NPI), and informant version of the Apathy Evaluation Scale (AES) between MCI, mild AD dementia, and mild DLB groups using Kruskal-Wallis test with Dunn-Bonferroni correction for post-hoc analyses. We compared sex, living situation, and caregiver demographics between three groups using chi-square test. We performed correlation analysis between the score of each psychological test and the scores of SF-DEM-J within group using Spearman’s rank correlation coefficient.Results:For SF-DEM-J, the score of section 2 (communicating with others) was significantly worse in mild AD dementia than in mild DLB. The scores of section 1 (spending with others) and section 3 (sensitivity to others) and the total score did not significantly differ between three groups. The score of section 1 was significantly associated with MMSE in MCI, with anxiety and disinhibition of NPI, and AES in mild AD dementia, and with GDS in mild DLB. The score of section 2 was significantly associated with AES in MCI and mild AD dementia, with UCLA-LS in MCI, and with the length of education in mild DLB. The score of section 3 was significantly associated with agitation and irritability of NPI in MCI and mild AD dementia. The total score was associated with UCLA-LS and AES in MCI, and with AES in mild AD dementia.Conclusion:Factors affecting social functioning differed between MCI, mild AD dementia, and mild DLB. Apathy, agitation and irritability affected social functioning in MCI and mild AD dementia while depressive mood affected social functioning in mild DLB.

A - 61 The Impact of Metacognition on Everyday Functioning in Mild Cognitive Impairment and Dementia.

The purpose of this study was to evaluate the role of metacognition on everyday functioning in mild cognitive impairment and dementia. Participants included 44 healthy older controls, 57 individuals with mild cognitive impairment (MCI), and 26 individuals with Alzheimer's disease (ad). Participants were administered verbal and nonverbal memory tests and a visuospatial test. They made predictions about their performances before taking each test and then made postdictions about their performances after each test. Prediction and postdiction accuracy scores were calculated. Additionally, all participants took the Everyday Cognition (ECog) Scale. Regression analyses were conducted, separately for each diagnostic group, to determine the roles of prediction and postdiction accuracy on everyday functioning. For healthy older controls, prediction and postdiction accuracy on a visuospatial test significantly impacted overall everyday functioning. In MCI, prediction accuracy on a nonverbal memory test significantly impacted everyday functioning. Finally, in ad, postdiction accuracy on a nonverbal memory test significantly predicted everyday memory. Overall, metacognition predicts everyday functioning in healthy aging, MCI, and ad. For healthy aging and MCI, the ability to both accurately predict and retrospectively evaluate their own cognition impacts overall everyday functioning. With the increased cognitive impairment of ad, only the ability to retrospectively evaluate performances impacts everyday memory.

Safety and feasibility of transcutaneous vagus nerve stimulation in mild cognitive impairment: VINCI-AD study protocol

BackgroundOver 55 million adults are living with dementia globally, which is projected to reach 157 million by 2050. Mild cognitive impairment (MCI), a syndrome of memory impairment with intact activities of daily living, may precede dementia by several years. Around 5–15% of individuals with MCI convert to dementia annually. Novel treatments which delay progression of MCI to dementia are urgently needed. Transcutaneous vagal nerve stimulation (tVNS) is a non-invasive neuromodulation technique that targets the vagus nerve. Importantly, tVNS has been shown to improve cognition in healthy volunteers, but has not been extensively examined as a potential therapeutic approach in MCI. VINCI-AD will examine the safety and feasibility of tVNS in older adults with MCI.DesignVINCI-AD is an investigator-led, single-site, single-blind, sham-controlled crossover pilot study which aims to assess the safety and feasibility of tVNS in 40 participants with amnestic MCI. All participants will attend for three consecutive study visits during which they will be randomised to receive no stimulation (baseline), active tVNS stimulation (stimulation at cymba conchae of left ear) or sham tVNS stimulation (at earlobe). Safety will be primarily assessed by ascertainment of adverse events. Further safety assessment will examine the impact of acute tVNS on subjective (orthostatic symptoms), peripheral (finometry-based blood pressure) and central (assessed via Near Infrared Spectroscopy [NIRS]) haemodynamic responses to active stand. Feasibility will be determined using a custom-designed occupational assessment of device usability. Exploratory secondary analysis in VINCI-AD will examine the potential impact of acute tVNS on associative memory, spatial memory and inhibitory control to inform sample size estimates for future trials of tVNS in older adults with MCI.DiscussionVINCI-AD will report on the safety (adverse events/haemodynamic responses to active stand) and feasibility of tVNS as a potential therapeutic option in MCI. Detailed reporting of study eligibility and completion rates will be reported. Exploratory analysis will examine the potential cognitive benefits of acute tVNS on cognitive function in MCI to report potential effect sizes that may inform future clinical trials in this cohort.Trial registrationhttps://clinicaltrials.gov/ct2/show/NCT05514756. Trial Registration Number NCT05514756 (24th August 2022 for this protocol, version 1.0.)

Brain reserve is associated with cognition in AD and MCI patients with different vascualr risk factors status

AbstractBackgroundDementia due to Alzheimer’s disease (AD) is the major type of dementias in the world. In addition to amyloid plaques and neurofibrillary tangles, cerebrovascular disease is another important pathophysiological cause of AD. Cerebrovascular disease is highly associated with vascular risk factors (VRFs). Well‐treated VRFs might decrease the risk and progression of AD. However, findings on the impact of VRFs treatment status on cognitive decline after the diagnosis of AD established are unclear, and there is no direct evidence supporting well‐treated VRFs can slow down the AD progression.MethodThis study recruited mild cognitive impairment (MCI) and mild AD patients (CDR = 0.5 or 1) with at least one VRF from at Taichung Veteran General Hospital. The treatment status of the VRFs was identified and all participants were evaluated by a standard neuropsychological test battery. We collected the participants’ brain MRI done within one year and performed Apolipoprotein E genotyping. FreeSurfer was used for structural MRI reconstruction and calculated total gray matter volume, hippocampus volume, and AD signature cortical thickness. Cerebrovascular lesions, including perivascular spaces in centrum semiovale, basal ganglia and presence of lobar cerebral microbleeds (LCMBs), and the volume of white matter hyperintensities were estimated by visual rating scales and Lesion Segmentation Tool for Statistical Parametric Mapping. We analyzed the relationships among the treatment status of VRFs, neuropsychological tests, and brain MRI.ResultWe recruited 61 patients in this study. Four patients refused to keep involving the study, 6 patients were not compatible with the criteria of MCI and AD after neuropsychiatric testing, and 4 patients’ brain MRI images cannot be analyzed after quality checked. The remaining 47 patients (15 MCI patients and 32 AD patients) constituted the final sample for analysis. The patients with well‐controlled VRFs present with similar cognitive function compared to the patients with partially‐controlled VRFs even though the more severe hippocampal atrophy was noted in the patients with well controlled VRFs. The severity of white matter hyperintensities and other cerebrovascular lesions are not correlated with the cognitive function in MCI and AD patients.ConclusionBrain reserve in the AD and MCI patients with well‐controlled VRFs might contribute cognitive function

Brain amyloid-β deposition associated functional connectivity changes of ultra-large structural scale in mild cognitive impairment.

In preclinical Alzheimer's disease, neuro-functional changes due to amyloid-β (Aβ) deposition are not synchronized in different brain lobes and subcortical nuclei. This study aimed to explore the correlation between brain Aβ burden, connectivity changes in an ultra-large structural scale, and cognitive function in mild cognitive impairment. Participants with mild cognitive impairment were recruited and underwent florbetapir (F18-AV45) PET, resting-state functional MRI, and multidomain neuropsychological tests. AV-45 standardized uptake value ratio (SUVR) and functional connectivity of all participants were calculated. Of the total 144 participants, 72 were put in the low Aβ burden group and 72 in the high Aβ burden group. In the low Aβ burden group, all connectivities between lobes and nuclei had no correlation with SUVR. In the high Aβ burden group, SUVR showed negative correlations with the Subcortical-Occipital connectivity (r=-0.36, P = 0.02) and Subcortical-Parietal connectivity (r=-0.26, P = 0.026). Meanwhile, in the high Aβ burden group, SUVR showed positive correlations with the Temporal-Prefrontal connectivity (r = 0.27, P = 0.023), Temporal-Occipital connectivity (r = 0.24, P = 0.038), and Temporal-Parietal connectivity (r = 0.32, P = 0.006). Subcortical to Occipital and Parietal connectivities had positive correlations with general cognition, language, memory, and executive function. Temporal to Prefrontal, Occipital, and Parietal connectivities had negative correlations with memory function, executive function, and visuospatial function, and a positive correlation with language function. In conclusion, Individuals with mild cognitive impairment with high Aβ burden have Aβ-related bidirectional functional connectivity changes between lobes and subcortical nuclei that are associated with cognitive decline in multiple domains. These connectivity changes reflect neurological impairment and failed compensation.

Preliminary evidence for developing safe and efficient fecal microbiota transplantation as potential treatment for aged related cognitive impairments.

Recent studies have reported that gut microbiota is closely associated with cognitive fuction. Fecal microbiota transplantation (FMT) may be a potential treatment for cognitive impairment, but its efficacy in patients with cognitive impairment is unknown. This study aimed to investigate the safety and efficacy of FMT for cognitive impairment treatment. Five patients aged 54-80 years (three women) were enrolled in this single-arm clinical trial from July 2021 to May 2022. The Montreal Cognitive Assessment-B (MoCA-B), Activities of Daily Living (ADL), and the cognitive section of the Alzheimer's Disease Assessment Scale (ADAS-Cog) were assessed at days 0, 30, 60, 90, and 180. Additionally, stool and serum samples were obtained twice before FMT was administered and six months after the treatment. The structure of fecal microbiota was analyzed by 16S RNA gene sequencing. Serum samples were analyzed for metabolomics and lipopolysaccharide (LPS)-binding proteins by liquid chromatography-mass spectrometry and enzyme-linked immunosorbent assay, respectively. Safety was assessed based on adverse events, vital signs, and laboratory parameters during FMT and the follow-up period. The MoCA, ADL, and ADAS-Cog scores of patients with mild cognitive impairment (patients C and E) after FMT were improved or maintained compared with those before transplantation. However, patients with severe cognitive impairment (patients A, B, and D) had no worsening of cognitive scores. Fecal microbiota analysis showed that FMT changed the structure of gut microbiota. The results of serum metabolomics analysis suggested that there were significant changes in the serum metabolomics of patients after FMT, with 7 up-regulated and 28 down-regulated metabolites. 3b,12a-dihydroxy-5a-cholanoic acid, 25-acetylvulgaroside, deoxycholic acid, 2(R)-hydroxydocosanoic acid, and P-anisic acid increased, while bilirubin and other metabolites decreased. KEFF pathway analysis indicated that the main metabolic pathways were bile secretion and choline metabolism in cancer. No adverse effects were reported throughout the study. In this pilot study, FMT could maintain and improve cognitive function in mild cognitive impairment by changing gut microbiota structure and affecting serum metabolomics. Fecal bacteria capsules were safe. However, further studies are needed to evaluate the safety and efficacy of fecal microbiota transplantation. ClinicalTrials.gov Identifier: CHiCTR2100043548.

Effects of candesartan on cerebral microvascular function in mild cognitive impairment: Results of two clinical trials.

Cerebral microvascular dysfunction is commonly seen in Alzheimer's disease (AD) and vascular cognitive impairment (VCI). Cerebrovascular reactivity (CVR) to CO2 reflects cerebral microvascular health and may be modulated by the renin-angiotensin system (RAS). This study aimed to investigate the effects of RAS modulation on CVR in individuals with mild cognitive impairment (MCI) due to underlying vascular or AD etiologies. This study presents findings of candesartan's effects on the secondary outcomes of two double-blind randomized clinical trials of 12-month therapy of candesartan versus lisinopril in VCI (CALIBREX (Candesartan vs Lisinopril Effects on the Brain and Endothelial Function in Executive MCI)) and candesartan versus placebo in prodromal AD (Candesartan's Effects on Alzheimer's Disease and Related Biomarkers (CEDAR)). Primary outcome results of these trials have been reported in previous publications. Participants underwent identical brain blood oxygenation level dependent (BOLD)-CVR in response to a 2-min CO2 challenge at baseline and 12 months. Regions of interest and voxel-wise CVR maps were derived from BOLD signal changes during CO2 challenge. CVR effects were compared between candesartan and lisinopril (CALIBREX) and candesartan and placebo (CEDAR) using mixed-model repeated measures. Data from 102 participants in the CALIBREX study (mean age = 65 years, 45% female, 63% African American) and 59 in the CEDAR study (mean age = 67 years, 32% female, 20% African American) were analyzed. Candesartan was associated with improved whole brain CVR compared to placebo in the CEDAR study (adjusted within-group mean difference for candesartan = 0.27 (95% confidence interval (CI) = 0.006, 0.53) vs placebo = -0.17 (95% CI = 0.42, 0.08), p-value = 0.018), and compared to lisinopril in the CALIBREX study (adjusted within-group mean difference for candesartan = 0.28 (95% CI = 0.10, 0.46) vs lisinopril = -0.08 (95% CI = -0.31, 0.14), p-value = 0.012), independent of blood pressure. In an exploratory meta-analysis of the two trials, improved CVR in the hippocampus was linked to improved attention and working memory (p = 0.044) and a trend for improved executive function (p = 0.087) with candesartan therapy. This study suggests that candesartan is associated with improved microvascular function in MCI, and these findings are independent of its blood pressure effect in these VCI and prodromal AD populations.

The Effects of Cognitive Rehabilitation Targeting Frontal Lobe Executive Function in Mild Cognitive Impairment

The Effects of Cognitive Rehabilitation Targeting Frontal Lobe Executive Function in Mild Cognitive Impairment

The Learning of Memory Support System in Individuals with Mild Cognitive Impairment

AbstractBackgroundThe syndrome of mild cognitive impairment (MCI) is classified into different subtypes– amnestic MCI (aMCI) and non‐amnestic MCI based on cognitive domains impacted, while different underlying disease etiologies cause the impairments. The Memory Support System (MSS), a memory‐support tool which utilizes a calendar/planner, has been shown to have positive impact on daily functioning in MCI (Chandler et al., 2017). We have previously shown that cognitive impairment severity and personality traits are associated with MSS learning (De Wit et al., 2021; Khayoun et al., 2021). In this study, we hypothesized that 1) participants with single domain aMCI (SD‐aMCI) will have higher MSS learning scores than multi‐domain aMCI (MD‐aMCI), and 2) participants with suspected Alzheimer’s disease (AD) etiology will have lower MSS learning scores than other etiologies.MethodParticipants (mean age = 75.2) underwent daily MSS training between 2017 and 2021 as part of the 10‐day Mayo Clinic HABIT program. The MSS learning success score (LSS) was determined by how far participants progressed in three learning phases of increasing difficulty: Acquisition (0‐2 points), Application (3‐4 points), and Adaptation (5‐6 points; Greenway et al., 2008). Ordinal logistic regression analysis was used to predict MSS learning scores between SD‐aMCI (n = 142) versus MD‐aMCI (n = 119), and AD etiology (n = 213) versus other neurodegenerative etiologies (n = 57). Dementia Rating Scale‐2 scores (Jurica, 2001) were included to control for cognitive severity.ResultCompared to participants with SD‐aMCI, those with MD‐aMCI had 54.1% lower odds of having higher LSS at training end (p = .004), after controlling for cognitive impairment severity. AD versus other etiology’s impact on LSS was nonsignificant.ConclusionParticipants with MD‐aMCI showed poorer MSS learning efficiency than participants with SD‐aMCI. Etiology did not impact MSS learning. Results suggest having more than just memory impairment (e.g., additional language or executive dysfunction) reduces MSS learning, regardless of overall impairment level. Additional MSS training may be needed to facilitate learning for these individuals.