Acquired mild Cognitive Impairment in adults with Down syndrome: Age related prevalence derived from single point assessment data normed by degree of intellectual disability.

Background: Age-related cerebrovascular and neuroinflammatory processes have been independently identified as key mechanisms of Alzheimer’s disease (AD), although their interactive effects have yet to be fully examined. Objective: The current study examined 1) the influence of pulse pressure (PP) and inflammatory markers on AD protein levels and 2) links between protein biomarkers and cognitive function in older adults with and without mild cognitive impairment (MCI). Methods: This study included 218 ADNI (81 cognitively normal [CN], 137 MCI) participants who underwent lumbar punctures, apolipoprotein E (APOE) genotyping, and cognitive testing. Cerebrospinal (CSF) levels of eight pro-inflammatory markers were used to create an inflammation composite, and amyloid-beta 1–42 (Aβ 42), phosphorylated tau (p-tau), and total tau (t-tau) were quantified. Results: Multiple regression analyses controlling for age, education, and APOE ɛ4 genotype revealed significant PP x inflammation interactions for t-tau (B = 0.88, p = 0.01) and p-tau (B = 0.84, p = 0.02); higher inflammation was associated with higher levels of tau within the MCI group. However, within the CN group, analyses revealed a significant PP x inflammation interaction for Aβ 42 (B = –1.01, p = 0.02); greater inflammation was associated with higher levels of Aβ 42 (indicative of lower cerebral amyloid burden) in those with lower PP. Finally, higher levels of tau were associated with poorer memory performance within the MCI group only (p s < 0.05). Conclusion: PP and inflammation exert differential effects on AD CSF proteins and provide evidence that vascular risk is associated with greater AD pathology across our sample of CN and MCI older adults.

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A Preliminary Analysis of Hearing Loss and Its Association With Mild Cognitive Impairment

Innovation in Aging ◽

10.1093/geroni/igaa057.1461 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

pp. 451-452

Author(s):

Mary Caroline Yuk ◽

Rebecca Allen ◽

Marcia Hay-McCutcheon ◽

Dana Carroll ◽

Anne Halli-Tierney

Keyword(s):

Hearing Loss ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Emotional Health ◽

Medical Center ◽

Pearson Correlation ◽

Well Being ◽

Hearing Screening ◽

Community Dwelling ◽

Age Related

Abstract Age related hearing loss, or presbycusis, is a global condition that is increasing in its prevalence. Despite being one of the most common chronic conditions among the older population, there is much more to understand about its association with other aspects of physical and emotional health and well-being. Current research is suggesting that hearing loss is more prevalent in those with cognitive impairment compared to those without cognitive impairment. This study analyzed the incidence of hearing loss and its linkage to mild cognitive impairment in a community-dwelling geriatric population. With the increasing prevalence of this condition in both rural and urban communities of Alabama, it becomes a more pressing matter to understand comorbidities and risk factors for future decline in functioning. This study was conducted in an interdisciplinary geriatrics primary care outpatient clinic in a Family, Internal, and Rural Medicine department affiliated with a university medical center in the Deep South. Ninety-one participants completed the Montreal Cognitive Assessment (MoCA) and a hearing screening. Hearing screenings were conducted in quiet rooms in the medical center using Phonak hearing screening cards. Detection of 500, 1000, 2000, and 4000 Hz tones was assessed. Pearson correlation analyses demonstrated an association between hearing loss mild cognitive impairment. Poorer hearing was significantly associated with lower scores on the MoCA. Conducting behavioral health screenings like this in other primary geriatrics clinics and community settings could improve care and identification of patient needs by integrating important data regarding comorbidities and independent living.

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Multimodal measurement approach to identify individuals with mild cognitive impairment: study protocol for a cross-sectional trial

BMJ Open ◽

10.1136/bmjopen-2020-046879 ◽

2021 ◽

Vol 11 (5) ◽

pp. e046879

Author(s):

Bernhard Grässler ◽

Fabian Herold ◽

Milos Dordevic ◽

Tariq Ali Gujar ◽

Sabine Darius ◽

...

Keyword(s):

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Statistical Analysis ◽

Cognitive Decline ◽

Cognitive Performance ◽

Classification Accuracy ◽

Multimodal Approach ◽

Cross Sectional ◽

Age Related ◽

Age Related Cognitive Decline

IntroductionThe diagnosis of mild cognitive impairment (MCI), that is, the transitory phase between normal age-related cognitive decline and dementia, remains a challenging task. It was observed that a multimodal approach (simultaneous analysis of several complementary modalities) can improve the classification accuracy. We will combine three noninvasive measurement modalities: functional near-infrared spectroscopy (fNIRS), electroencephalography and heart rate variability via ECG. Our aim is to explore neurophysiological correlates of cognitive performance and whether our multimodal approach can aid in early identification of individuals with MCI.Methods and analysisThis study will be a cross-sectional with patients with MCI and healthy controls (HC). The neurophysiological signals will be measured during rest and while performing cognitive tasks: (1) Stroop, (2) N-back and (3) verbal fluency test (VFT). Main aims of statistical analysis are to (1) determine the differences in neurophysiological responses of HC and MCI, (2) investigate relationships between measures of cognitive performance and neurophysiological responses and (3) investigate whether the classification accuracy can be improved by using our multimodal approach. To meet these targets, statistical analysis will include machine learning approaches.This is, to the best of our knowledge, the first study that applies simultaneously these three modalities in MCI and HC. We hypothesise that the multimodal approach improves the classification accuracy between HC and MCI as compared with a unimodal approach. If our hypothesis is verified, this study paves the way for additional research on multimodal approaches for dementia research and fosters the exploration of new biomarkers for an early detection of nonphysiological age-related cognitive decline.Ethics and disseminationEthics approval was obtained from the local Ethics Committee (reference: 83/19). Data will be shared with the scientific community no more than 1 year following completion of study and data assembly.Trial registration numberClinicalTrials.gov, NCT04427436, registered on 10 June 2020, https://clinicaltrials.gov/ct2/show/study/NCT04427436.

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Animal Models of Down Syndrome

The Oxford Handbook of Down Syndrome and Development ◽

10.1093/oxfordhb/9780190645441.013.4 ◽

2021 ◽

Author(s):

Anna J. Moyer ◽

Roger H. Reeves

Keyword(s):

Down Syndrome ◽

Cognitive Impairment ◽

Intellectual Disability ◽

Animal Models ◽

Brain Regions ◽

Laboratory Mice ◽

Tremendous Progress ◽

New Treatments ◽

And Function ◽

Early Developmental

Is intellectual disability a treatable feature of persons with Down syndrome? Researchers have made tremendous progress in the last 30 years, from creating the first mouse model of Down syndrome to completing the first major clinical trial for cognitive impairment in people with Down syndrome. Until recently, normalizing brain development and function seemed too lofty a goal, and indeed, even proposing a candidate therapy requires answering a number of difficult questions. How does trisomy 21, a molecular diagnosis, cause the clinical phenotypes of Down syndrome? When, where, and how do trisomic genes act to disrupt normal development and which genes are involved with which outcomes? Which brain regions and behaviors are most impaired? Is there an early developmental window of time during which treatments are most effective? This article discusses how animal models such as laboratory mice can be used to understand intellectual disability and to develop new treatments for cognitive impairment.

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Sex-dependent Pathological Aging Effect on Caudate Functional Connectivity in Mild Cognitive Impairment

10.21203/rs.3.rs-1005572/v1 ◽

2021 ◽

Author(s):

Zhengshi Yang ◽

Jessica Z.K. Caldwell ◽

Jeffrey L. Cummings ◽

Aaron Ritter ◽

Jefferson W. Kinney ◽

...

Keyword(s):

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Functional Connectivity ◽

Aging Effect ◽

Analysis Of Covariance ◽

Aging Effects ◽

Mixed Effect ◽

Effect Analysis ◽

Pathological Aging ◽

Age Related

Abstract Purpose To assess the pathological aging effect on caudate functional connectivity among mild cognitive impairment (MCI) participants and examine whether and how sex and amyloid contribute to this process. Materials and Methods 277 functional magnetic resonance imaging (fMRI) sessions from 163 cognitive normal (CN) older adults and 309 sessions from 139 participants with MCI were included as the main sample in our analysis. Pearson’s correlation was used to characterize the functional connectivity (FC) between caudate and each brain region, then caudate nodal strength was computed to quantify the overall caudate FC strength. Association analysis between caudate nodal strength and age was carried out in MCI and CN separately using linear mixed effect (LME) model with covariates (education, handedness, sex, Apolipoprotein E4 and intra-subject effect). Analysis of covariance was conducted to investigate sex, amyloid status and their interaction effects on aging with the fMRI data subset having amyloid status available. LME model was applied to women and men separately within MCI group to evaluate aging effects on caudate nodal strength and each region’s connectivity with caudate. We then evaluated the roles of sex and amyloid status in the associations of neuropsychological scores with age or caudate nodal strength. An independent cohort was used to validate the sex-dependent aging effects in MCI. Results The MCI group had significantly stronger age-related increase of caudate nodal strength compared to the CN group. Analyzing women and men separately revealed that the aging effect on caudate nodal strength among MCI participants was significant only for women (left: P=6.23x10−7, right: P=3.37x10−8), but not for men (P>0.3 for bilateral caudate). The aging effects on caudate nodal strength were not significantly mediated by brain amyloid burden. Caudate connectivity with ventral prefrontal cortex substantially contributed to the aging effect on caudate nodal strength in women with MCI. Higher caudate nodal strength is significantly related to worse cognitive performance in women but not in men with MCI. Conclusion Sex modulates the pathological aging effects on caudate nodal strength in MCI regardless of amyloid status. Caudate nodal strength may be a sensitive biomarker of pathological aging in women with MCI.

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Proteomic profiles of prevalent mild cognitive impairment and Alzheimer's disease among adults with Down syndrome

Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring ◽

10.1002/dad2.12023 ◽

2020 ◽

Vol 12 (1) ◽

Author(s):

Melissa Petersen ◽

Fan Zhang ◽

Sharon J. Krinsky‐McHale ◽

Wayne Silverman ◽

Joseph H. Lee ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Down Syndrome ◽

Cognitive Impairment ◽

Mild Cognitive Impairment

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Effects of moxibustion on symptoms of mild cognitive impairment: protocol of a systematic review and meta-analysis

BMJ Open ◽

10.1136/bmjopen-2019-033910 ◽

2020 ◽

Vol 10 (4) ◽

pp. e033910 ◽

Cited By ~ 1

Author(s):

Tao Zhang ◽

Lin-Peng Wang ◽

Gui-Ling Wang ◽

Jing-Qing Sun ◽

Xue-Wen Mao ◽

...

Keyword(s):

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Full Text ◽

Evaluation System ◽

Risk Of Bias ◽

Assessment Tools ◽

Controlled Trials ◽

Cochrane Central Register ◽

Age Related ◽

Text Database

IntroductionMild cognitive impairment (MCI) is considered the intermediate phase between normal age-related cognitive decline and dementia. Moxibustion has gained increased popularity for the management of MCI in China.This study aimed to evaluate the effects and safety of moxibustion on symptoms of MCI.Methods and analysisFour English databases and six Chinese databases will be searched from their inception to October 2019: Embase, MEDLINE, Cochrane Central Register of Controlled Trials, Allied and Complementary Medicine Database, China National Knowledge Infrastructure, Chongqing VIP Chinese Science and Technology Periodical Database, Wanfang Database, SinoMed, China Doctoral Dissertations Full-text Database and the China Master’s Theses Full-text Database. Only clinical randomised controlled trials and the first period in randomised cross-over trial related to moxibustion for MCI will be included. The primary outcomes include the improvement of cognitive function, as measured by validated assessment tools. The secondary outcomes include changes in the activity of daily living scale, effective rate and the incidences of adverse events. The selection of studies, data extraction and risk of bias assessment will be carried out by two independent reviewers. Review Manager V.5.3 software will be used for statistical analyses. Heterogeneity test, data synthesis and subgroup analysis will be performed if necessary. The risk of bias of included studies will be assessed by theCochrane Handbookrisk of bias tool. Evidence quality will be evaluated using the Grading of Recommendations Assessment, Development and Evaluation system.Ethics and disseminationEthics approval is not required as no private information from individuals are collected. The results will be published in a peer-reviewed journal or disseminated in relevant conferences.Trial registration numberCRD42018112657.

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P4-301: Efficacy and safety of MMFS-01, a synapse density enhancer, for restoring cognitive ability in age-related mild cognitive impairment: A randomized, double-blind, placebo-controlled trial

Alzheimer s & Dementia ◽

10.1016/j.jalz.2015.08.131 ◽

2015 ◽

Vol 11 (7S_Part_19) ◽

pp. P900-P901

Author(s):

Guosong Liu ◽

Jason Gregory Weinger ◽

Zhong-Lin Lu ◽

Feng Xue ◽

Safa Sadeghpour

Keyword(s):

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Cognitive Ability ◽

Controlled Trial ◽

Efficacy And Safety ◽

Double Blind ◽

Double Blind Placebo ◽

Age Related ◽

Synapse Density

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Mild cognitive impairment (MCI) twenty years on

International Psychogeriatrics ◽

10.1017/s1041610211002067 ◽

2011 ◽

Vol 24 (1) ◽

pp. 1-5 ◽

Cited By ~ 10

Author(s):

Karen Ritchie ◽

Craig W Ritchie

Keyword(s):

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Cognitive Decline ◽

Brain Aging ◽

Cognitive Change ◽

Cognitive Disorder ◽

Everyday Functioning ◽

Normal Limits ◽

Age Related ◽

The Usa

Cognitive decline has commonly been considered an inevitable result of brain aging and has been of clinical interest principally because of related difficulties with everyday functioning. Since the 1990s the “normality” of age-related cognitive decline has been called into question, being commonly attributed to a number of underlying disorders. Numerous concepts have been proposed which link subclinical cognitive change to pathological states (mild cognitive disorder, mild neurocognitive disorder, mild cognitive impairment). Of these, mild cognitive impairment (MCI) has become the most popular, driven on the one hand by industrial interests seeking to extend new dementia treatments for a more prevalent subclinical syndrome, and on the other by researchers attempting to identify at-risk populations. MCI has been both criticized for “medicalizing” behavior still within normal limits (Stephan et al., 2008; Moreira et al., 2008) and welcomed in that it suggests cognitive decline with aging may not be inevitable, but rather due to abnormalities which could ultimately be treated. Recently, in both Europe (DuBois et al., 2007) and the USA (Albert et al., 2011), panels of experts have scrutinized the concept of MCI and more broadly the pre-dementia stages of neurodegenerative diseases and offered new research diagnostic criteria. These proposed criteria have highlighted the (potential) value of biomarkers in assisting diagnosis, although some have considered the elevation of biomarkers to this level of importance in diagnosing disease before dementia develops to be premature given both the extent and quality of diagnostic biomarker data currently available (McShane et al., 2011a; 2011b).

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