scholarly journals Myo-Inositol Levels in the Dorsal Hippocampus Serve as Glial Prognostic Marker of Mild Cognitive Impairment in Mice

2021 ◽  
Vol 13 ◽  
Author(s):  
Tim Ebert ◽  
Daniel E. Heinz ◽  
Suellen Almeida-Corrêa ◽  
Renata Cruz ◽  
Frederik Dethloff ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Prognostic Marker ◽  
Dorsal Hippocampus ◽  
Pantothenic Acid ◽  
Resonance Spectroscopy ◽  
Related Disorder ◽  
Age Related ◽  
Before And After

Dementia is a devastating age-related disorder. Its therapy would largely benefit from the identification of susceptible subjects at early, prodromal stages of the disease. To search for such prognostic markers of cognitive impairment, we studied spatial navigation in male BALBc vs. B6N mice in combination with in vivo magnetic resonance spectroscopy (1H-MRS). BALBc mice consistently showed higher escape latencies than B6N mice, both in the Water Cross Maze (WCM) and the Morris water maze (MWM). These performance deficits coincided with higher levels of myo-inositol (mIns) in the dorsal hippocampus before and after training. Subsequent biochemical analyses of hippocampal specimens by capillary immunodetection and liquid chromatography mass spectrometry-based (LC/MS) metabolomics revealed a higher abundance of glial markers (IBA-1, S100B, and GFAP) as well as distinct alterations in metabolites including a decrease in vitamins (pantothenic acid and nicotinamide), neurotransmitters (acetylcholine), their metabolites (glutamine), and acetyl-L-carnitine. Supplementation of low abundant acetyl-L-carnitine via the drinking water, however, failed to revert the behavioral deficits shown by BALBc mice. Based on our data we suggest (i) BALBc mice as an animal model and (ii) hippocampal mIns levels as a prognostic marker of mild cognitive impairment (MCI), due to (iii) local changes in microglia and astrocyte activity, which may (iv) result in decreased concentrations of promnesic molecules.

scholarly journals Age-related mild cognitive deficit: a ready-to-use concept?

2003 ◽  
Vol 5 (1) ◽  
pp. 61-76
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Elderly Patients ◽  
Cognitive Deficit ◽  
Magnetization Transfer ◽  
Cognitive Status ◽  
Resonance Spectroscopy ◽  
First Line ◽  
Frequent Type ◽  
Age Related

For better management of mild cognitive impairment in elderly patients, clinicians should be provided with instruments to detect early changes and predict their progression. To define this cognitive status between optimal and pathological aging, many concepts have been proposed, which actually describe various conditions and provide more or less precise criteria, leaving room for variable implementation. As a consequence, application of these criteria gave highly variable prevalence rates, Neuropathological studies indicate that the different criteria have variable power in detecting incipient Alzheimer's disease (AD) and suggest that the transition between mild cognitive impairment and ÀD is not merely quantitative. Follow-up studies have produced, according to the criteria used, a 2.5% to 16,6% annual rate for progression toward dementia, and have also shown that the criteria differ in their stability and predictive power. Baseline cognitive performances have some predictive value, but are difficult to apply in first-line medicine. Investigational techniques (structural and functional imaging, magnetic resonance spectroscopy, magnetization transfer imaging, cerebrospinal fluid neuro-chemistry, and apolipoprotein E genotype) are promising tools in the early diagnosis of AD, which remains the most frequent type of dementia in elderly people and probably the most frequent type developed by patients with mild cognitive deficit. The final goal is to offer early treatment to those patients who will evolve towards dementia, once they can be identified, in the case of AD, recent findings question the adequacy of cholinergic replacement therapies. In its current state, the criteria for mild cognitive deficit are hardly transferable to first-line medicine. However, disseminating the concept could help increase the sensitivity of general practitioners to the importance of cognitive complaints and signs in their elderly patients.

scholarly journals T2 heterogeneity as an in vivo marker of microstructural integrity in medial temporal lobe subfields in ageing and mild cognitive impairment

2020 ◽  
Author(s):  
Alfie R. Wearn ◽  
Volkan Nurdal ◽  
Esther Saunders-Jennings ◽  
Michael J. Knight ◽  
Christopher R. Madan ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Temporal Lobe ◽  
Medial Temporal Lobe ◽  
Learning Task ◽  
Quantitative Mri ◽  
Associate Learning ◽  
Age Related ◽  
Brain Changes

ABSTRACTA better understanding of early brain changes that precede loss of independence in diseases like Alzheimer’s disease (AD) is critical for development of disease-modifying therapies. Quantitative MRI, such as T2 relaxometry, can identify microstructural changes relevant to early stages of pathology. Recent evidence suggests heterogeneity of T2 may be a more informative measure of early pathology than absolute T2. Here we test whether T2 markers of brain integrity precede the volume changes we know are present in established AD and whether such changes are most marked in medial temporal lobe (MTL) subfields known to be most affected early in AD. We show that T2 heterogeneity was greater in people with mild cognitive impairment (MCI; n=49) compared to healthy older controls (n=99) in all MTL subfields, but this increase was greatest in MTL cortices, and smallest in dentate gyrus. This reflects the spatio-temporal progression of neurodegeneration in AD. T2 heterogeneity in the entorhinal cortex also predicted cognitive decline over a year in people with MCI, where measures of volume or T2 in any other subfield or whole hippocampus could not. Increases in T2 heterogeneity in MTL cortices may reflect localised pathological change and may present as one of the earliest detectible brain changes prior to atrophy. Finally, we describe a mechanism by which memory, as measured by accuracy and reaction time on a paired associate learning task, deteriorates with age. Age-related memory deficits were explained in part by lower subfield volumes, which in turn were directly associated with greater T2 heterogeneity. We propose that tissue with high T2 heterogeneity represents extant tissue at risk of permanent damage but with the potential for therapeutic rescue. This has implications for early detection of neurodegenerative disease.

scholarly journals Posterior Cingulate Lactate as a Metabolic Biomarker in Amnestic Mild Cognitive Impairment

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Kurt E. Weaver ◽  
Todd L. Richards ◽  
Rebecca G. Logsdon ◽  
Ellen L. McGough ◽  
Satoshi Minoshima ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Disease Progression ◽  
Hippocampal Volume ◽  
Amnestic Mild Cognitive Impairment ◽  
Resonance Spectroscopy ◽  
Compensatory Response ◽  
Posterior Cingulate ◽  
Therapeutic Trials

Mitochondrial dysfunction represents a central factor within the pathogenesis of the Alzheimer’s disease (AD) spectrum. We hypothesized that in vivo measurements of lactate (lac), a by-product of glycolysis, would correlate with functional impairment and measures of brain health in a cohort of 15 amnestic mild cognitive impairment (aMCI) individuals. Lac was quantified from the precuneus/posterior cingulate (PPC) using 2-dimensional J-resolved magnetic resonance spectroscopy (MRS). Additionally, standard behavioral and imaging markers of aMCI disease progression were acquired. PPC lac was negatively correlated with performance on the Wechsler logical memory tests and on the minimental state examination even after accounting for gray matter, cerebral spinal fluid volume, and age. No such relationships were observed between lac and performance on nonmemory tests. Significant negative relationships were also noted between PPC lac and hippocampal volume and PPC functional connectivity. Together, these results reveal that aMCI individuals with a greater disease progression have increased concentrations of PPC lac. Because lac is upregulated as a compensatory response to mitochondrial impairment, we propose that J-resolved MRS of lac is a noninvasive, surrogate biomarker of impaired metabolic function and would provide a useful means of tracking mitochondrial function during therapeutic trials targeting brain metabolism.

Elevated Inflammatory Markers and Arterial Stiffening Exacerbate Tau but Not Amyloid Pathology in Older Adults with Mild Cognitive Impairment

2021 ◽  
pp. 1-13
Author(s):  
Alexandra L. Clark ◽  
Alexandra J. Weigand ◽  
Kelsey R. Thomas ◽  
Seraphina K. Solders ◽  
Lisa Delano-Wood ◽  
...  
Keyword(s):  
Older Adults ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Inflammatory Markers ◽  
Memory Performance ◽  
Cognitive Testing ◽  
Interactive Effects ◽  
Protein Biomarkers ◽  
Age Related ◽  
T Tau

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.

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

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.

scholarly journals In vivo nucleus basalis of Meynert degeneration in mild cognitive impairment with Lewy bodies

2021 ◽  
Vol 30 ◽  
pp. 102604
Author(s):  
Julia Schumacher ◽  
John-Paul Taylor ◽  
Calum A. Hamilton ◽  
Michael Firbank ◽  
Ruth A. Cromarty ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Lewy Bodies ◽  
Nucleus Basalis ◽  
Nucleus Basalis Of Meynert

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

BMJ Open ◽  
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.

Sign in / Sign up

Export Citation Format

Share Document