Criteria For Mild Cognitive Impairment Research Articles

Maximizing the "Functional" in the Functional External Memory Aid Tool for Patient-Centered Treatment Planning in Mild Cognitive Impairment.

The Functional External Memory Aid Tool (FEMAT) is an 11-item performance-based measure that simulates everyday tasks (e.g., medication management) to measure one's use of compensation (e.g., pill organizer). The FEMAT is not a norm-referenced diagnostic tool; rather, it is designed to provide clinicians with information about a patient's function and compensation in a standardized format. To provide further evidence for validity of the FEMAT, the purpose of this study was to conduct a mixed-methods analysis of FEMAT responses to operationalize the types of behaviors elicited during test administration. We adopted an embedded single-case study design to analyze the FEMAT administrations of 12 community-dwelling female participants, ages 73-90 years, who met criteria for mild cognitive impairment. These participants were part of the original validation sample during which they completed the FEMAT (Version 1.0) in a single session with an assessor. Sessions were video-recorded and transcribed. We analyzed the data qualitatively in two phases using theme and subtheme codes and then quantitatively analyzed the data for response trends. Our thematic analysis revealed four themes to operationalize participants' verbal and behavioral FEMAT responses: (a) used an external memory aid (EMA), (b) described using a strategy, (c) discussed memory and comprehension, and (d) discussed functional information. While completing the FEMAT, most participants described using a strategy (85%) and discussed their self-perceived memory and comprehension (33%). Several subthemes also emerged within each theme (e.g., self-perceived memory strengths and barrier). Our analysis suggests that beyond a 4-point item score, the FEMAT elicits behavioral (e.g., used an EMA) and verbal (e.g., discussion of health information) content that may be useful for person-centered treatment planning. This study is part of a comprehensive research agenda establishing the evidence for the validity of the FEMAT to support its use to inform person-centered treatment approaches.

Prevalence of Unrecognized Cognitive Impairment in Federally Qualified Health Centers

There is a need for early and equitable detection of cognitive impairment among older adults. To examine the prevalence of unrecognized cognitive impairment among older adults receiving primary care from federally qualified health centers (FQHCs). This cross-sectional study was conducted at 5 FQHCs providing primary care in Indianapolis, Indiana, between 2021 and 2023. Participants were adults aged 65 years and older, without a diagnosis of mild cognitive impairment (MCI), dementia, or severe mental illness. Data analysis was performed from September 2023 to April 2024. The primary outcome was a diagnosis of dementia or MCI, as determined by an interdisciplinary clinical team using data from structured patient and study partner interviews, medical record reviews, and a detailed cognitive assessment, including neuropsychological testing. Differences between participants determined to have normal cognition, MCI, and dementia were assessed statistically using analysis of variance for continuous variables, χ2 or Fisher exact tests for categorical variables, or Fisher exact test alone when expected cell counts were 5 or less. A total of 844 eligible individuals were consecutively approached, 294 consented to participate, and 204 completed the study (mean [SD] age, 70.0 [5.1] years; 127 women [62.3%]). One hundred eight participants (52.9%) were African American, 5 (2.5%) were Hispanic, 199 (97.5%) were not Hispanic, and 90 (44.1%) were White. The mean (SD) duration of education was 13.1 (2.6) years, and the mean (SD) Area Deprivation Index score was 78.3 (19.9), indicating a high level of neighborhood disadvantage. In total, 127 patients (62.3%) met the diagnostic criteria for MCI, 25 (12.3%) had dementia, and 52 (25.5%) had no cognitive impairment. Compared with non-Hispanic White individuals and after adjusting for age, sex, and education level, African American individuals were more than twice as likely to have MCI or dementia (odds ratio, 2.73; 95% CI, 1.38-5.53; P = .02). This cross-sectional study found that unrecognized cognitive impairment is ubiquitous among older adults from underrepresented, minoritized racial and ethnic groups and those who are socially vulnerable receiving primary care from FQHCs. To overcome the disparity in early detection of cognitive impairment, timely, equitable, scalable, and sustainable detection approaches need to be developed.

Analysis of the effectiveness of a computerized cognitive stimulation program designed from Occupational Therapy according to the level of cognitive reserve in older adults in Primary Care: Stratified randomized clinical trial protocol

Normal aging presents subtle cognitive changes that can be detected before meeting the criteria for Mild cognitive impairment (MCI). Older people with low cognitive reserve and who receive limited cognitive stimulation are at greater risk of deterioration. In this regard, cognitive stimulation (CS) has been identified as an intervention that reduces this risk, provided that its design takes into account the differences in the level of cognitive reserve (CR) acquired throughout life and the baseline level of cognitive functioning. The general objective of this study is to evaluate, through a randomized clinical trial, the effectiveness of a computerized cognitive stimulation program, designed and adapted from Occupational Therapy based on the level of cognitive reserve in older adults in Primary Care. 100 participants will be randomized in a stratified manner according to the level of cognitive reserve (low/moderate/high), assigning 50 participants to the control group and 50 participants to the intervention group. The intervention group will carry out a computerized cognitive stimulation intervention designed and adapted from occupational therapy according to the level of cognitive reserve, through the “stimulus” platform. The main result expected to be achieved is the improvement of higher brain functions. As secondary results, we expect that those cognitive aspects most vulnerable to aging will decrease more slowly (in areas such as memory, executive function, attention and processing speed), and that the cognitive reserve of the participants will increase, in addition to being able to balance gender differences in these aspects. We think that these results can have a positive impact on the creation of adapted, meaningful and stimulating CS programs in older adults to prevent MCI and experience healthier aging.

Japanese Subgroup Analyses from EMERGE and ENGAGE, Phase 3 Clinical Trials of Aducanumab in Patients with Early Alzheimer’s Disease

BackgroundGlobal prevalence and incidence of dementia continue to rise at a rapid rate. There is a need for new Alzheimer’s disease (AD) treatments globally. Aducanumab is a human monoclonal antibody that selectively targets aggregated soluble amyloid beta oligomers and insoluble amyloid beta fibrils. In June 2021, aducanumab was approved by the US Food and Drug Administration for the treatment of AD under the accelerated approval pathway.ObjectivesWe evaluated the efficacy, safety, biomarker and pharmacokinetics (PK) of aducanumab in Japanese subgroups in EMERGE and ENGAGE studies.DesignEMERGE and ENGAGE were two randomized, double-blind, placebo-controlled, global, phase 3 studies of aducanumab in patients with early AD (mild cognitive impairment due to AD or mild AD dementia).SettingThese studies involved 348 sites in 20 countries. PARTICIPANTS: Participants enrolled in Japan included 121 (7.4% of total 1638 in EMERGE) and 100 (6.1% of total 1647 in ENGAGE) patients (aged 50–85 years with confirmed amyloid pathology) who met clinical criteria for mild cognitive impairment due to AD or mild AD dementia.InterventionParticipants were randomly assigned 1:1:1 to receive aducanumab low dose (3 or 6 mg/kg target dose), high dose (6 or 10 mg/kg target dose) or placebo via IV infusion once every 4 weeks over 76 weeks.MeasurementsThe primary outcome measure was change from baseline to Week 78 on the Clinical Dementia Rating Sum of Boxes (CDR-SB), an integrated scale that assesses both function and cognition. Other measures included safety assessments; secondary and tertiary clinical outcomes that assessed cognition, function, and behavior; biomarker endpoints (amyloid PET and plasma p-tau181); serum PK profiles and immunogenicity.ResultsResults from the Japanese subgroup analyses were generally consistent with those of the overall study population across endpoints, while a lower mean body weight (kg) and a smaller proportion of ApoE ε4 carriers were observed in the Japanese subgroup population. A treatment effect was observed in favor of aducanumab on the primary and secondary efficacy endpoints at Week 78 in EMERGE, but not ENGAGE. The incidence and type of adverse events in the Japanese subgroups were generally comparable to those observed in the overall study population; amyloid related imaging abnormalities (ARIA) were common treatment-related adverse events that appeared to be related to the aducanumab dose. ARIA incidence was generally lower in the Japanese subgroup compared with the overall population. Consistent with the overall data set, a robust dose-dependent decrease in amyloid beta levels as assessed with amyloid-PET and plasma p-tau181 was observed. Serum PK profiles and immunogenicity of aducanumab in Japanese population were consistent with the non-Japanese population.ConclusionEfficacy, safety, biomarker, and PK profiles of aducanumab were consistent between the Japanese subgroup and the overall population. A positive treatment effect of aducanumab on efficacy endpoints was observed in EMERGE, but not in ENGAGE.

Data-driven retrieval of population-level EEG features and their role in neurodegenerative diseases.

Electrophysiologic disturbances due to neurodegenerative disorders such as Alzheimer's disease and Lewy Body disease are detectable by scalp EEG and can serve as a functional measure of disease severity. Traditional quantitative methods of EEG analysis often require an a-priori selection of clinically meaningful EEG features and are susceptible to bias, limiting the clinical utility of routine EEGs in the diagnosis and management of neurodegenerative disorders. We present a data-driven tensor decomposition approach to extract the top 6 spectral and spatial features representing commonly known sources of EEG activity during eyes-closed wakefulness. As part of their neurologic evaluation at Mayo Clinic, 11 001 patients underwent 12 176 routine, standard 10-20 scalp EEG studies. From these raw EEGs, we developed an algorithm based on posterior alpha activity and eye movement to automatically select awake-eyes-closed epochs and estimated average spectral power density (SPD) between 1 and 45 Hz for each channel. We then created a three-dimensional (3D) tensor (record × channel × frequency) and applied a canonical polyadic decomposition to extract the top six factors. We further identified an independent cohort of patients meeting consensus criteria for mild cognitive impairment (30) or dementia (39) due to Alzheimer's disease and dementia with Lewy Bodies (31) and similarly aged cognitively normal controls (36). We evaluated the ability of the six factors in differentiating these subgroups using a Naïve Bayes classification approach and assessed for linear associations between factor loadings and Kokmen short test of mental status scores, fluorodeoxyglucose (FDG) PET uptake ratios and CSF Alzheimer's Disease biomarker measures. Factors represented biologically meaningful brain activities including posterior alpha rhythm, anterior delta/theta rhythms and centroparietal beta, which correlated with patient age and EEG dysrhythmia grade. These factors were also able to distinguish patients from controls with a moderate to high degree of accuracy (Area Under the Curve (AUC) 0.59-0.91) and Alzheimer's disease dementia from dementia with Lewy Bodies (AUC 0.61). Furthermore, relevant EEG features correlated with cognitive test performance, PET metabolism and CSF AB42 measures in the Alzheimer's subgroup. This study demonstrates that data-driven approaches can extract biologically meaningful features from population-level clinical EEGs without artefact rejection or a-priori selection of channels or frequency bands. With continued development, such data-driven methods may improve the clinical utility of EEG in memory care by assisting in early identification of mild cognitive impairment and differentiating between different neurodegenerative causes of cognitive impairment.

The criteria used to rule out mild cognitive impairment impact dementia incidence rates in subjective cognitive decline

BackgroundThe research criteria for subjective cognitive decline (SCD) exclude mild cognitive impairment (MCI), but do not stipulate the use of specific MCI criteria. This study compared different approaches to defining (i.e., excluding) MCI during the ascertainment of SCD, focusing on the impact on dementia incidence rates in SCD.MethodsThis cohort study utilized routine healthcare data collected in the Essex Memory Clinic from 1999 to 2023. Two different operationalizations of the SCD criteria were used to categorize the cohort into two SCD patient samples. One sample was based on local clinical practice – MCI was excluded according to the Winblad criteria (this sample was termed SCDWinblad). The other sample was created via the retrospective application of the Jak/Bondi criteria for the exclusion of MCI (termed SCDJak/Bondi). Only patients aged ≥ 55 years at baseline with ≥ 12 months follow-up were considered for inclusion. The initial clinical/demographic characteristics of the samples were compared. Rates of incident dementia were calculated for each sample, and unadjusted and Mantel-Haenszel-adjusted incidence rate ratios were calculated to compare dementia incidence between the SCD samples.ResultsThe Essex Memory Clinic database included 2,233 patients in total. The SCD and study eligibility criteria were used to select SCDWinblad (n = 86) and SCDJak/Bondi (n = 185) samples from the database. Median follow-up (3 years) did not differ between the two samples. The SCDJak/Bondi sample was significantly older than the SCDWinblad at first assessment (median age: 74 versus 70 years) and had poorer scores on tests of global cognition, immediate and delayed verbal recall, and category fluency. Following adjustment for age, the dementia incidence rate ratio [95% confidence interval] was 3.7 [1.5 to 9.3], indicating a significantly greater rate of progression to dementia in SCDJak/Bondi.ConclusionsThis study highlights that the approach used to ascertain SCD has important implications for both SCD phenotypes and prognosis. This underscores the importance of how MCI is operationalized within SCD studies. More broadly, the findings add to a growing body of work indicating that objective cognition should not be overlooked in SCD, and offer a potential explanation for the heterogeneity across the SCD prognostic literature.

Glymphatic function from diffusion-tensor MRI to predict conversion from mild cognitive impairment to dementia in Parkinson’s disease

BackgroundAlthough brain glymphatic dysfunction is a contributing factor to the cognitive deficits in Parkinson’s disease (PD), its role in the longitudinal progression of cognitive dysfunction remains unknown.ObjectiveTo investigate the glymphatic function in PD with mild cognitive impairment (MCI) that progresses to dementia (PDD) and to determine its predictive value in identifying individuals at high risk for developing dementia.MethodsWe included 64 patients with PD meeting criteria for MCI and categorized them as either progressed to PDD (converters) (n = 29) or did not progress to PDD (nonconverters) (n = 35), depending on whether they developed dementia during follow-up. Meanwhile, 35 age- and gender-matched healthy controls (HC) were included. Bilateral diffusion-tensor imaging analysis along the perivascular space (DTI-ALPS) indices and enlarged perivascular spaces (EPVS) volume fraction in bilateral centrum semiovale, basal ganglia (BG), and midbrain were compared among the three groups. Correlations among the DTI-ALPS index and EPVS, as well as cognitive performance were analyzed. Additionally, we investigated the mediation effect of EPVS on DTI-ALPS and cognitive function.ResultsPDD converters had lower cognitive composites scores in the executive domains than did nonconverters (P < 0.001). Besides, PDD converters had a significantly lower DTI-ALPS index in the left hemisphere (P < 0.001) and a larger volume fraction of BG-PVS (P = 0.03) compared to HC and PDD nonconverters. Lower DTI-ALPS index and increased BG-PVS volume fraction were associated with worse performance in the global cognitive performance and executive function. However, there was no significant mediating effect. Receiver operating characteristic analysis revealed that the DTI-ALPS could effectively identify PDD converters with an area under the curve (AUC) of 0.850.ConclusionThe reduction of glymphatic activity, measured by the DTI-ALPS, could potentially be used as a non-invasive indicator in forecasting high risk of dementia conversion before the onset of dementia in PD patients.

Data-driven sequence of cognitive decline in people with Parkinson’s disease

BackgroundUnderstanding the sequential progression of cognitive impairments in Parkinson’s disease (PD) is crucial for elucidating neuropathological underpinnings, refining the assessment of PD-related cognitive decline stages and enhancing early identification for...

The prevalence of mild cognitive impairment in breast cancer patients receiving chemotherapy according to the criteria of the National Institute on Aging-Alzheimer's Association (NIA-AA).

Breast cancer patients receiving chemotherapy can develop cognitive impairment. There is no gold standard for defining cognitive impairment. We applied the National Institute on Aging-Alzheimer's Association (NIA-AA) criteria for mild cognitive impairment (MCI) to determine its prevalence in breast cancer patients receiving adjuvant chemotherapy and examine differences between patients with and without MCI. We used pre-existing cognitive data on 5 neuropsychological test outcomes (verbal memory, processing speed, executive functioning, and verbal fluency) gathered from 240 breast cancer patients who received adjuvant conventional (n = 154) or high-dose chemotherapy (n = 86). Assessments occurred 6 or 12months post-chemotherapy and results were compared with data from 66 women without cancer. MCI was defined by the following: (i) presence of concern regarding a change in cognition, (ii) impairment in one or more cognitive tests (1.5 standard deviation below a normative mean), (iii) preservation of independence in functional abilities, and (iv) the absence of dementia. Twenty percent (n = 49) of breast cancer patients who received chemotherapy (conventional therapy n = 29 (12%), high-dose therapy = 20 (8.3%)) met the criteria for MCI, compared with 7.6% (n = 5) of controls. Prevalence was significantly different between patients and controls (P = 0.020, and corrected for IQ P < 0.001). Patients with MCI had significant lower education levels (P < 0.002) and premorbid IQ (P = 0.001) compared with patients without MCI. Twenty percent of breast cancer patients treated with chemotherapy met NIA-AA criteria for MCI, compared with 7.6% of the controls. These criteria, which include formal test performance as well as a person's symptoms and functional status, can be useful in clinical practice and scientific research.

0441 Sleep Disturbance in MCI: A Pilot Study of a Cognitive Behavioural Therapy Digital Intervention (SUCCEED)

Abstract Introduction Insomnia is common in older adults with mild cognitive impairment (MCI) and predicts future cognitive decline. Cognitive Behavioural Therapy for insomnia (CBT-I) is the first-line treatment for insomnia but is often unavailable. We tested the feasibility of a randomised controlled trial comparing 12-weeks of digital CBT-I vs wait-listed control in older adults with MCI and insomnia. Methods This was an investigator-initiated (NCT05568381), parallel open-label randomised-controlled feasibility trial. Participants were randomised to digital CBT-I (Sleepio, 6-weekly sessions) or a wait-listed control (3 fortnightly online modules of a sleep health education package) via a secure centralised platform which was also used to collect the outcome data. This study was undertaken remotely without in-person visits. Potential participants were recruited through online advertising and a memory clinic in Sydney, Australia. Those who met initial eligibility were invited to a screening and informed consent telehealth consultation. Inclusion criteria included adults aged ≥50 years, with an Insomnia Severity Index (ISI)&amp;gt;10, who met the clinical criteria of MCI on a neuropsychological battery (performed over telehealth for participants recruited online). The primary outcomes were the proportion of participants who met screening and randomisation criteria. A secondary outcome was the effect sizes and 95%CIs of the difference in ISI between the groups at week 12. Results Recruitment occurred March 23, 2023 to August 11, 2023 stopping when we reached our pre-defined sample size (digital CBT-I=19; control=21; 30 females; mean [SD] age=59.7 years [7.3]; ISI=17.0 [3.7]). 37% of participants issued a pre-screening number (n=246), were eligible to attend online screening. 47% of those issued a screening number (n=90) were eligible to be randomised (n=42). All randomised participants (n=40) were recruited through the online pathway. At 12-weeks there was a difference in ISI between the digital CBT-I (mean±SE 7.8±1.1 points) and control groups (13.7±1.05 points) (Cohen’s D [95%CI] -1.6 [-2.4 to 2.1]). 79% of participants completed ≥4 out of the CBT-I 6 sessions. All adverse events were minor and transient. Conclusion This population can be recruited through online pathways and follow the protocol as well as adhere to the intervention of this remotely conducted trial. Support (if any) CogSleep CRE Seed Funding Grant. BigHealth- intervention in-kind.

Validity of Montreal Cognitive Assessment to Detect Cognitive Impairment in Individuals with Type 2 Diabetes.

Guidelines recommend screening older people (> 60-65years) with type 2 diabetes (T2D) for cognitive impairment, as it has implications in the management of diabetes. The Montreal Cognitive Assessment (MoCA) is a sensitive test for the detection of mild cognitive impairment (MCI) in the general population, but its validity in T2D has not been established. We administered MoCA to patients with T2D (age ≥ 60years) and controls (no T2D), along with a culturally validated neuropsychological battery and functional activity questionnaire. MCI was defined as performance in one or more cognitive domains ≥ 1.0 SD below the control group (on two tests representing a cognitive domain), with preserved functional activities. The discriminant validity of MoCA for the diagnosis of MCI at different cut-offs was ascertained. We enrolled 267 patients with T2D and 120 controls; 39% of the participants with T2D met the diagnostic criteria for MCI on detailed neuropsychological testing. At the recommended cut-off on MoCA (< 26), the sensitivity (94.2%) was high, but the specificity was quite low (29.5%). The cut-off score of < 23 showed an optimal trade-off between sensitivity (69.2%), specificity (71.8%), and diagnostic accuracy (70.8%). The cut-off of < 21 exhibited the highest diagnostic accuracy (74.9%) with an excellent specificity (91.4%), a good positive and negative predictive value (78.5% and 73.7%, respectively). The recommended screening cut-off point on MoCA of < 26 has a suboptimal specificity and may increase the referral burden in memory clinics. A lower cut-off of < 21 on MoCA maximizes the diagnostic accuracy. Interactive Visual Abstract available for this article.

Discriminant Potential of the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) in Greek Older Adults with Subjective Cognitive Decline and Mild Cognitive Impairment.

Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAS-Cog) is a widely used screening tool for detecting older adults with Alzheimer's disease among their cognitively healthy peers. A previous study in Greek population showed that ADAS-Cog-Greek (G) is a valid tool and can identify people with Alzheimer's disease from older adult control group; however, there is no current data about whether ADAS-Cog can differentiate older adults with mild cognitive impairment (MCI) from those who have subjective cognitive decline (SCD). The current study aimed to examine the discriminant potential of ADAS-Cog-G in Greek older adults who meet the criteria for SCD or MCI. Four hundred eighty-two community-dwelling older adults, visitors of the Greek Alzheimer Association and Related Disorders, were enrolled in the current study. One hundred seventy-six of them met the criteria for SCD and three hundred six had MCI. Path analysis applied to the data showed that age, as well as educational level affected ADAS-Cog-G performance. Results showed that the cut-off scores, which better discriminate people with SCD from MCI as well as their sensitivity and specificity values, were extracted in participants with high educational level (13 educational years<) and mainly under the age of 75 years. The current study provided evidence concerning the discriminant potential of ADAS-Cog-G to differentiate older adults with SCD from those with MCI in the Greek population, and therefore contributes to the relevant literature on the field.

Cognitive Impairment Is Part of the Phenotype of Cerebellar Ataxia, Neuropathy, Vestibular Areflexia Syndrome (CANVAS).

Little is known about the impact of the cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) on cognition. Our objective was to determine the frequency and severity of cognitive impairment in RFC1-positive patients and describe the pattern of deficits. Participants underwent a comprehensive neuropsychological assessment. Volume of the cerebellum and its lobules was measured in those who underwent a 3 Tesla-magnetic resonance scan. Twenty-one patients underwent a complete assessment, including 71% scoring lower than the cutoff at the Montreal Cognitive assessment and 71% having a definite cerebellar cognitive affective/Schmahmann syndrome. Three patients had dementia and seven met the criteria of mild cognitive impairment. Severity of cognitive impairment did not correlate with severity of clinical manifestations. Performance at memory and visuospatial functions tests negatively correlated with the severity of cerebellar manifestations. Cognitive manifestations are frequent in RFC1-related disorders. They should be included in the phenotype and screened systematically. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Comment on article: "Risk factors associated with cognitive impairment in older adults: cross-sectional study"

In patients with mild cognitive impairment, the activities of basic and instrumented daily living are preserved, this distinguishes it from major cognitive impairment. In the baseline state of the cross-sectional study on risk factors associated with cognitive impairment, patients with dependence in basic daily living activities were observed, so it is possible to incur an incorrect attribution of this factor, since functional dependence is usually a consequence of cognitive impairment and not one of the factors that precede it, so an-error is made when using the diagnostic criteria for mild cognitive impairment. Cross-sectional studies identify risk factors by reconstructing phenomenology, which can lead to attributing as a cause a factor that, in reality, is a consequence of the outcome.

Abnormal functional connectivity of the occipital thalamus with the superior occipital gyrus is associated with mild cognitive impairment in elderly individuals with primary insomnia

AbstractStudy objectivesPrimary insomnia (PI) triggers a decline in cognitive function, and the thalamus plays an integral role in this process; however, the mechanisms are unclear. The purpose of this study was to investigate the altered functional connectivity (FC) of the thalamus in PI patients with mild cognitive impairment (MCI) and to explore the potential neural mechanisms of thalamic involvement in these patients.MethodsThis case–control study was conducted in older adults from various communities in Fuzhou, China with a PI diagnosis. These participants underwent neuropsychological assessment and were matched in a 1:2 ratio to the healthy control (HC) group and the PI group according to sex, age, and education level. Resting‐state functional magnetic resonance imaging was used to explore changes in thalamic FC in PI patients. To further compare changes in thalamic and whole‐brain FC, we further divided the PI group into cognitively normal patients and patients with MCI according to the diagnostic criteria for MCI. The relationship between abnormal FC and cognitive function was investigated.ResultsThe 28 HCs and 58 participants with PI showed significant differences in Montreal Cognitive Assessment (MoCA) scores (p = .044). In comparison to the HC group, the PI group showed enhanced FC of the occipital thalamus with the left inferior occipital gyrus, right lingual gyrus, left middle temporal gyrus, left superior marginal gyrus, left dorsolateral superior frontal gyrus, and right anterior central gyrus. The MoCA total score and the executive function, attention, and abstraction scores of PI patients with MCI (PI–MCI) were worse than those of PI patients without MCI. In comparison to the simple PI group, FC was enhanced in the PI–MCI group between the left occipital thalamus and the middle occipital gyrus, and between the right occipital thalamus and the right superior frontal gyrus, left middle frontal gyrus, right superior occipital gyrus, and orbital inferior frontal gyrus. There was a significant negative correlation between the MoCA total score and the enhanced FC between the right occipital thalamus and right superior occipital gyrus (r = −.419, p = .042).ConclusionThe early onset of cognitive impairment in patients with PI is associated with altered FC between the thalamus and the cortex. Enhanced FC between the thalamus and the visual cortex, that is, the superior occipital gyrus, which is involved in attentional processing, may play a role in the early onset of cognitive impairment in insomnia patients. Moreover, due to the fact that PI patients “overdraw” the compensatory capacity of these brain regions earlier, the PI–MCI may fall into the abyss of “decompensation” faster and face more severe cognitive impairments.

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

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

Mild cognitive impairment in Huntington's disease: challenges and outlooks.

Although Huntington's disease (HD) has classically been viewed as an autosomal-dominant inherited neurodegenerative motor disorder, cognitive and/or behavioral changes are predominant and often an early manifestation of disease. About 40% of individuals in the presymptomatic period of HD meet the criteria for mild cognitive impairment, later progressing to dementia. The heterogenous spectrum of cognitive decline is characterized by deficits across multiple domains, particularly executive dysfunctions, but the underlying pathogenic mechanisms are still poorly understood. Investigating the pathophysiology of cognitive changes may give insight into important and early neurodegenerative events. Multimodal imaging revealed circuit-wide gray and white matter degenerative processes in several key brain regions, affecting prefronto-striatal/cortico-basal ganglia circuits and many other functional brain networks. Studies in transgenic animal models indicated early synaptic dysfunction, deficient neurotrophic transport and other molecular changes contributing to neuronal death. Synaptopathy within the cerebral cortex, striatum and hippocampus may be particularly important in mediating cognitive and neuropsychiatric manifestations of HD, although many other neuronal systems are involved. The interaction of mutant huntingtin protein (mHTT) with tau and its implication for cognitive impairment in HD is a matter of discussion. Further neuroimaging and neuropathological studies are warranted to better elucidate early pathophysiological mechanisms and to develop validated biomarkers to detect patients' cognitive status during the early stages of the condition significantly to implement effective preventing or management strategies.

The prevalence of mild cognitive impairment in Gulf War veterans: a follow-up study.

Gulf War Illness (GWI), also called Chronic Multisymptom Illness (CMI), is a multi-faceted condition that plagues an estimated 250,000 Gulf War (GW) veterans. Symptoms of GWI/CMI include fatigue, pain, and cognitive dysfunction. We previously reported that 12% of a convenience sample of middle aged (median age 52 years) GW veterans met criteria for mild cognitive impairment (MCI), a clinical syndrome most prevalent in older adults (e.g., ≥70 years). The current study sought to replicate and extend this finding. We used the actuarial neuropsychological criteria and the Montreal Cognitive Assessment (MoCA) to assess the cognitive status of 952 GW veterans. We also examined regional brain volumes in a subset of GW veterans (n = 368) who had three Tesla magnetic resonance images (MRIs). We replicated our previous finding of a greater than 10% rate of MCI in four additional cohorts of GW veterans. In the combined sample of 952 GW veterans (median age 51 years at time of cognitive testing), 17% met criteria for MCI. Veterans classified as MCI were more likely to have CMI, history of depression, and prolonged (≥31 days) deployment-related exposures to smoke from oil well fires and chemical nerve agents compared to veterans with unimpaired and intermediate cognitive status. We also replicated our previous finding of hippocampal atrophy in veterans with MCI, and found significant group differences in lateral ventricle volumes. Because MCI increases the risk for late-life dementia and impacts quality of life, it may be prudent to counsel GW veterans with cognitive dysfunction, CMI, history of depression, and high levels of exposures to deployment-related toxicants to adopt lifestyle habits that have been associated with lowering dementia risk. With the Food and Drug Administration's recent approval of and the VA's decision to cover the cost for anti-amyloid β (Aβ) therapies, a logical next step for this research is to determine if GW veterans with MCI have elevated Aβ in their brains.

Preventing cognitive decline by reducing BP target (PCOT): A randomized, pragmatic, multi-health systems clinical trial

BackgroundGrowing evidence suggests that intensive lowering of systolic blood pressure (BP) may prevent mild cognitive impairment (MCI) and dementia. However, current guidelines provide inconsistent recommendations regarding optimal BP targets, citing safety concerns of excessive BP lowering in the diverse population of older adults. We are conducting a pragmatic trial to determine if an implementation strategy to reduce systolic BP to <130 and diastolic BP to <80 mmHg will safely slow cognitive decline in older adults with hypertension when compared to patients receiving usual care. MethodsThe Preventing Cognitive Decline by Reducing BP Target Trial (PCOT) is an embedded randomized pragmatic clinical trial in 4000 patients from two diverse health-systems who are age ≥ 70 years with BP >130/80 mmHg. Participants are randomized to the intervention arm or usual care using a permuted block randomization within each health system. The intervention is a combination of team-based care with clinical decision support to lower home BP to <130/80 mmHg. The primary outcome is cognitive decline as determined by the change in the modified Telephone Interview for Cognitive Status (TICS-m) scores from baseline. As a secondary outcome, patients who decline ≥3 points on the TICS-m will complete additional cognitive assessments and this information will be reviewed by an expert panel to determine if they meet criteria for MCI or dementia. ConclusionThe PCOT trial will address the effectiveness and safety of hypertension treatment in two large health systems to lower BP targets to reduce risk of cognitive decline in real-world settings.

The interaction of obesity with susceptible gene polymorphisms in the relationship with mild cognitive impairment.

Mild cognitive impairment (MCI) in the elderly is threatening the mental health of the elderly, and the interaction of some factors is worth exploring. This study aims to explore the interactions of obesity and gene polymorphisms in the relationship with MCI. A total of 2555 community resident dwellings include 444 participants who met MCI criteria recruited from the Ningxia province of China. Fourteen MCI-susceptible single nucleotide polymorphisms were detected using a high-throughput mass spectrometer. The interaction was examined by performing the multifactor dimensionality reduction model and unconditional logistic regression model. Logistic regression showed that obesity (OR = 1.42, 95%CI: 1.04-1.94), rs2075650G allele carrying (OR = 17.95, 95%CI: 1.32-244.95), rs11556505T allele carrying (OR = 0.06, 95%CI: 0.01-0.87) were statistically associated with MCI. Multifactor dimensionality reduction analysis showed a strong antagonistic effect between obesity and rs4402960 (Interaction dendrogram between obesity and rs4402960 is red) and a weak synergy effect on rs7901695 (Interaction dendrogram between obesity and rs7901695 is green). The hierarchical analysis showed obesity is a risk factor for MCI in the non-rs4402960T allele carrier group (OR = 1.55, 95%CI: 1.02-2.35). This study found that obesity is an independent risk factor for MCI, and the interactions with MCI-susceptible gene polymorphisms suggest a possible precision preventive intervention program should be developed to reduce the risk of MCI among individuals with obesity in the community.