Atrophy In Mild Cognitive Impairment Research Articles

The impact of physical exercise on hippocampal atrophy in mild cognitive impairment and Alzheimer's disease: a meta-analysis.

Physical activity (PA) is a promising therapeutic for Alzheimer's disease (AD). Only a handful of meta-analyses have studied the impact of PA interventions on regional brain volumes, and none to date has solely included studies on effect of PA on regional brain volumes in individuals with cognitive impairment (CI). In this meta-analysis, we examined whether there is support for the hypothesis that PA interventions positively impact hippocampal volume (HV) in individuals with CI. We also assessed whether the level of CI [mild CI (MCI) vs. AD] impacted this relationship. We identified six controlled trials that met inclusion criteria. These included 236 participants with AD, MCI, or preclinical AD. Data were extracted and analyzed following Cochrane guidelines. We used a random-effects model to estimate the mean change in HV pre- and post-exercise intervention. Forest plots, Hedges' g funnel plots, and Egger's test were used to assess unbiasedness and visualize intervention effects, and Tau 2 , Cochran's Q, and I 2 were calculated to assess heterogeneity. The primary analysis revealed a significant positive effect of PA on total HV. However, sub-group analyses indicated a significant preservation of HV only in individuals with MCI, but not in those with AD. Egger's test indicated no evidence of publication bias. Subgroup analyses also revealed significant heterogeneity only within the MCI cohort for the total and left HV. PA demonstrated a moderate, significant effect in preserving HV among individuals with MCI, but not AD, highlighting a therapeutic benefit, particularly in earlier disease stages.

Depression and Agitation Factors Are Related to Regional Brain Atrophy and Faster Longitudinal Cognitive Decline in Mild Cognitive Impairment.

Neuropsychiatric symptoms (NPS) are a common aspect of Alzheimer's disease (AD). Multiple studies have investigated its brain correlates, but it still remains unclear how they relate with brain atrophy in mild cognitive impairment (MCI). Our objective was to investigate brain volume in MCI patients as a function of NPS. We measured grey matter volume, neuropsychological status and NPS (Neuropsychiatric Inventory, NPI), in a sample of 81 MCI patients (43 females). Participants were divided in groups depending on presence (NPS+) or absence (NPS-) of NPS and on type of NPS. We found lower volume of left temporal pole in patients with depression compared to NPS- (p = 0.012), and in patients with agitation compared to NPS- in the right middle occipital gyrus (p = 0.003). We also found a significant correlation between volume of left temporal pole and MMSE (r(78) = 0.232, p = 0.019). Finally, NPS+ presented lower cross-sectional cognitive level than NPS- (t(79) = 1.79, p = 0.038), and faster cognitive decline (t(48) = -1.74, p = 0.044). Our results support the colocalization of structural damage as a possible mechanism underlying the relationship between MCI and depression and provide novel evidence regarding agitation. Moreover, our longitudinal evidence highlights the relevance of an adequate identification of NPS in MCI patients to identify those at risk of faster cognitive decline.

The Structural Changes of Frontal Subregions and Their Correlations with Cognitive Impairment in Patients with Alzheimer's Disease.

The frontal lobe is affected by Alzheimer's disease (AD) and mild cognitive impairment (MCI). However, we still lack sufficient understanding of subregion atrophy in the frontal cortex, and the relationship between subregions volume and cognitive decline in AD or MCI remains unclear. This study enrolled 434 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI), including 150 cognitively normals (CN), 187 subjects with MCI, and 97 patients with AD. The gray matter of frontal regions and subregions was divided based on the BNA-246 atlas and its volume was measured by voxel-based morphometry (VBM). Analysis of covariance was performed to compare the differences in frontal regions and subregions volume. Then, receiver operating characteristic (ROC) curve and the area under the curve (AUC) were used to analyze the discriminative ability of subregion volume to distinguish the three groups. In addition, we investigated the association of subregion volume with Mini-Mental State Examination (MMSE) score and Alzheimer's Disease Assessment Scale-Cognitive Behavior section (ADAS-cog) scores with age, gender, education, and the estimated total intracranial volume (eTIV) as covariates. In addition to the regions of frontal lobe atrophy found in previous studies, atrophy of the precentral gyrus (PrG) and some of its subregions were found in MCI. The volume of the right dorsal area 9/46 (MFG_7_1) was the best index to differentiate AD from CN, with an AUC value of 0.7. Moreover, we found that some subregions are associated with cognition in patients with MCI and AD. Frontal lobe atrophy in MCI is more extensive than we assumed. In addition, the volume of right MFG_7_1 has the potential to distinguish AD from CN.

Regional cerebral blood flow and brain atrophy in mild cognitive impairment and Alzheimer's disease.

A decline in the regional cerebral blood flow (CBF) is proposed to be one of the initial changes in the Alzheimer's disease process. To date, there are limited data on the correlation between CBF decline and gray matter atrophy in mild cognitive impairment (MCI) and AD patients. to investigate the association between CBF with the gray matter structural parameters such as cortical volume, surface area, and thickness in AD, MCI, and healthy controls (HC). Data from three groups of participants including 39 HC, 82 MCI, and 28 AD subjects were obtained from the Alzheimer's disease Neuroimaging Initiative (ADNI). One-way ANOVA and linear regression were used to compare data and find a correlation between structural parameters such as cortical volume, surface area, and thickness and CBF which measured by arterial spin labeling (ASL)-MRI. Our findings revealed a widespread significant correlation between the CBF and structural parameters in temporal, frontal, parietal, occipital, precentral gyrus, pericalcarine cortex, entorhinal cortex, supramarginal gyrus, fusiform, precuneus, and pallidum. CBF decline may be a useful biomarker for MCI and AD and accurately reflect the structural changes related to AD. According to the present results, CBF decline, as measured by ASL-MRI, is correlated with lower measures of structural parameters in AD responsible regions. It means that CBF decline may reflect AD-associated atrophy across disease progression and is also used as an early biomarker for AD and MCI diagnosis.

A multi-site, multi-participant magnetoencephalography resting-state dataset to study dementia: The BioFIND dataset

Early detection of Alzheimer's Disease (AD) is vital to reduce the burden of dementia and for developing effective treatments. Neuroimaging can detect early brain changes, such as hippocampal atrophy in Mild Cognitive Impairment (MCI), a prodromal state of AD. However, selecting the most informative imaging features by machine-learning requires many cases. While large publically-available datasets of people with dementia or prodromal disease exist for Magnetic Resonance Imaging (MRI), comparable datasets are missing for Magnetoencephalography (MEG). MEG offers advantages in its millisecond resolution, revealing physiological changes in brain oscillations or connectivity before structural changes are evident with MRI. We introduce a MEG dataset with 324 individuals: patients with MCI and healthy controls. Their brain activity was recorded while resting with eyes closed, using a 306-channel MEG scanner at one of two sites (Madrid or Cambridge), enabling tests of generalization across sites. A T1-weighted MRI is provided to assist source localisation. The MEG and MRI data are formatted according to international BIDS standards and analysed freely on the DPUK platform (https://portal.dementiasplatform.uk/Apply). Here, we describe this dataset in detail, report some example (benchmark) analyses, and consider its limitations and future directions.

Relationships between the Fear of COVID-19 Scale and regional brain atrophy in mild cognitive impairment.

Several studies have reported that the pandemic of coronavirus disease 2019 (COVID-19) influenced cognitive function in the elderly. However, the effect of COVID-19-related fear on brain atrophy has not been evaluated. In this study, we evaluated the relation between brain atrophy and the effect of COVID-19-related fear by analysing changes in brain volume over time using magnetic resonance imaging (MRI). Participants were 25 Japanese patients with mild cognitive impairment (MCI) or subjective cognitive decline (SCD), who underwent 1.5-tesla MRI scan twice, once before and once after the pandemic outbreak of COVID-19, and the Fear of Coronavirus Disease 2019 Scale (FCV-19S) assessment during that period. We computed regional brain atrophy per day between the 1st and 2nd scan, and evaluated the relation between the FCV-19S scores and regional shrinkage. There was significant positive correlation between the total FCV-19S score and volume reduction per day in the right posterior cingulate cortex. Regarding the subscales of FCV-19S, we found significant positive correlation between factor 2 of the FCV-19S and shrinkage of the right posterior cingulate cortex. There was positive correlation between the FCV-19S score and regional brain atrophy per day. Although it is already known that the psychological effects surrounding the COVID-19 pandemic cause cognitive function decline, our results further suggest that anxiety and fear related to COVID-19 cause regional brain atrophy.

The relationship between flutriciclamide PET uptake and grey matter atrophy in mild cognitive impairment and Alzheimer’s disease

AbstractBackgroundMicroglial activation plays a significant role in neuroinflammation in the neurodegenerative process. Microglial activation is characterised by the over‐expression of a mitochondrial protein (TSPO), that can be targeted by PET Tracers. This study aims to evaluate the relationship between [18F]GE180 PET uptake and grey matter atrophy.MethodIn this PET study, we evaluated microglial activation in mild cognitive impairment (MCI) and Alzheimer’s disease (AD) using the novel TSPO ligand flutriciclamide ([18F]GE180). Forty‐eight participants have been assesed with [18F]GE180 PET using arterial input. Spectral analysis was used to generate parametric maps of the impulse response function at 90 minutes. Additionally, hippocampal volume analysis was performed on structural magnetic resonance images (MRIs).ResultIn a group‐wise analysis a significant reduction in hippocampal volume was found between the AD and healthy controls cohorts. Hippocampal volume significantly negatively correlated with the IRF90 in the temporal lobe and occipital lobes as well as and composite region in AD patients compared to healthy controls.ConclusionIn this [18F]GE180 PET imaging study in AD/MCI cohort, we have demonstrated that there is hippocampal atrophy when [18F]GE180 PET goes up in AD patients. The results indicate that regional [18F]GE180 PET uptake has a close association with neurodegeneration of key memories processing centre.

B Vitamins Prevent Iron-Associated Brain Atrophy and Domain-Specific Effects of Iron, Copper, Aluminum, and Silicon on Cognition in Mild Cognitive Impairment.

Background:Metals, silicon, and homocysteine are linked to Alzheimer’s disease. B vitamin therapy lowers homocysteine and slows brain atrophy and cognitive decline in mild cognitive impairment (MCI).Objective:Examine metals and silicon as predictors of cognition/brain atrophy in MCI, their interaction with homocysteine and cysteine, and how B vitamins affect these relationships.Methods:MCI participants (n = 266, 77.6-year-old, 60.7% female) in VITACOG trial were randomized to receive daily folic acid (0.8 mg)/vitamin B12 (0.5 mg)/vitamin B6 (20 mg) (n = 133) or placebo for two years. At baseline and end-of-study, cranial MRIs were obtained from 168 participants, cognition was analyzed by neuropsychological tests, and serum iron, copper, arsenic, aluminum, and silicon quantified by inductively-coupled plasma mass spectrometry in 196 participants. Data were analyzed by bivariate and multiple regression.Results:Baseline iron, cysteine, and homocysteine were significantly associated with brain atrophy rate. Homocysteine effects on brain atrophy rate were modified by iron and cysteine. At baseline, iron, copper, aluminum, and silicon were significantly associated with one or more domains of cognition: semantic memory, verbal episodic memory, attention/processing speed, and executive function. At end-of-study, baseline iron, copper, aluminum, and silicon predicted cognition in at least one domain: semantic memory, verbal episodic memory, visuospatial episodic memory, attention/processing speed, and global cognition in the placebo but not the B vitamin group.Conclusion:Disparate effects of serum iron, copper, aluminum, silicon, and homocysteine on cognition and brain atrophy in MCI suggest that cognitive impairment is independent of brain atrophy. These factors showed domain-specific associations with cognition, which were abrogated by B vitamin therapy.

Association of Cerebral Ischemia With Corneal Nerve Loss and Brain Atrophy in MCI and Dementia.

IntroductionThis study assessed the association of cerebral ischemia with neurodegeneration in mild cognitive impairment (MCI) and dementia.MethodsSubjects with MCI, dementia and controls underwent assessment of cognitive function, severity of brain ischemia, MRI brain volumetry and corneal confocal microscopy.ResultsOf 63 subjects with MCI (n = 44) and dementia (n = 19), 11 had no ischemia, 32 had subcortical ischemia and 20 had both subcortical and cortical ischemia. Brain volume and corneal nerve measures were comparable between subjects with subcortical ischemia and no ischemia. However, subjects with subcortical and cortical ischemia had a lower hippocampal volume (P < 0.01), corneal nerve fiber length (P < 0.05) and larger ventricular volume (P < 0.05) compared to those with subcortical ischemia and lower corneal nerve fiber density (P < 0.05) compared to those without ischemia.DiscussionCerebral ischemia was associated with cognitive impairment, brain atrophy and corneal nerve loss in MCI and dementia.

Evaluation of Early Cerebral Atrophy in Mild Cognitive Impairment with Positive Amyloid PET using MRIVolumetric Measurement

Objective: To identify early cerebral atrophy by using magnetic resonance imaging (MRI) volumetric measurement to distinguish mild cognitive impairment (MCI) from normal aging. Materials and Methods: A retrospective study in 29 Alzheimer’s disease (AD) patients (mean 75.6±7.3 years), 11 MCI patients (mean 68.8±3.9 years), and 27 healthy control (HC) subjects (mean 69.3±4.7 years) was performed with analysis of neurological and neuropsychiatric test, and underwent 3T MRI with high-resolution 3D-T1W. Quantitative volumetric analysis of brain including surface area, cortical gray matter volume, cortical thickness, and hippocampal subfields was performed by using FreeSurfer software. Results: The diminishment of cortical gray matter volume and cortical thickness were involved in most of brain regions, predominantly in temporal lobe with statistical significance in AD compared with MCI and HC. Comparison between amyloid positron emission tomography (PET) positive MCI subjects and HC has statistically significant difference in most regions of hippocampal subfield. The highest accuracy of 90.01% with sensitivity of 50% and specificity of 100% were found at subiculum. A comparison between amyloid PET positive MCI subjects and amyloid PET negative MCI subjects revealed significant differences at right molecular layer, right/average GC-ML-DG, right CA2/3, right CA4, and average CA4 with good accuracy, sensitivity, and specificity. Conclusion: The present study confirmed improved sensitivity of MRI volumetric measurement with hippocampal subfield analysis to identify early stage of AD in MCI patients, at least compared with positive amyloid PET MCI. Study with higher number of subjects using this method to discriminate MCI and normal aging control would provide benefits as the screening tool in older population. Keywords: Hippocampal subfield; Volumetric analysis; Alzheimer’s disease; Mild cognitive impairment

Association between white matter hyperintensity load and grey matter atrophy in mild cognitive impairment is not unidirectional.

Neuroimaging measures of Alzheimer’s disease (AD) include grey matter volume (GMV) alterations in the Default Mode Network (DMN) and Executive Control Network (ECN). Small-vessel cerebrovascular disease, often visualised as white matter hyperintensities (WMH) on MRI, is often seen in AD. However, the relationship between WMH load and GMV needs further examination. We examined the load-dependent influence of WMH on GMV and cognition in 183 subjects. T1-MRI data from 93 Mild Cognitive Impairment (MCI) and 90 cognitively normal subjects were studied and WMH load was categorized into low, medium and high terciles. We examined how differing loads of WMH related to whole-brain voxel-wise and regional DMN and ECN GMV. We further investigated how regional GMV moderated the relationship between WMH and cognition. We found differential load-dependent effects of WMH burden on voxel-wise and regional atrophy in only MCI. At high load, as expected WMH negatively related to both ECN and DMN GMV, however at low load, WMH positively related to ECN GMV. Additionally, negative associations between WMH and memory and executive function were moderated by regional GMV. Our results demonstrate non-unidirectional relationships between WMH load, GMV and cognition in MCI.

Cerebrovascular disease influences hippocampal subfield atrophy in mild cognitive impairment

AbstractBackgroundDistinguishing between pure AD and AD with concomitant CVD is challenging due to overlapping pathogenesis such as cerebral accumulation of amyloid‐β (Aβ) plaques and neurofibrillary tangles. In recent years, hippocampal subfield volumes have been recommended over other neuroimaging markers of AD due to its functionally distinct nature and higher accuracy. However to date, patterns of hippocampal subfield atrophy in prodromal AD with and without concomitant CVD remain largely unexplored. This study investigates the associations and differences in hippocampal subfield volumes in mild cognitive impairment (MCI) with significant/non‐significant cerebrovascular disease (MCI+/‐CVD).Method176 MCI subjects (mean age=65.56 years, SD=8.77) underwent neuropsychological assessments and magnetic resonance imaging. White matter hyperintensities were quantified using modified Fazekas ratings. Subjects with Fazekas ratings of ≥ 8 were categorised as MCI+CVD. Demographics, brain volumetric measurements for grey and white matter volumes, periventricular and deep white matter hyperintensities and hippocampal subfields were examined in MCI+/‐CVD. Multiple linear regressions were conducted for MCI+CVD to examine predictions of hippocampal subfield volumes on cognitive performance.ResultMCI+CVD (N=39) performed worse than MCI‐CVD in all neuropsychological assessments. MCI+CVD had significantly smaller volumes in the hippocampal tail (p=.042), subiculum (p=.015), CA1 (p=.023), molecular layer (p=.009) and fimbria (p=.025). MCI+CVD had significant associations between hippocampal subfield volumes and cognitive performance: hippocampal tail with global cognition (p=.049) and visuospatial skills (p=.004); subiculum with global cognition (p=.026) and episodic memory (p=.001), molecular layer with global cognition (p=.049) and episodic memory (p=.010) and fimbria with episodic memory (p=.038).ConclusionMCI+CVD has significantly greater hippocampal subfield atrophy, with atrophy of the hippocampal tail, subiculum, molecular layer and fimbria correlating to poorer performance in global cognition, visuospatial skills and episodic memory. The findings of this study may guide future research in investigating longitudinal changes in hippocampal atrophy in MCI+/‐CVD and the corresponding implications on cognitive performance.

Graph Theory Analysis Reveals Resting-State Compensatory Mechanisms in Healthy Aging and Prodromal Alzheimer's Disease.

Several theories of cognitive compensation have been suggested to explain sustained cognitive abilities in healthy brain aging and early neurodegenerative processes. The growing number of studies investigating various aspects of task-based compensation in these conditions is contrasted by the shortage of data about resting-state compensatory mechanisms. Using our proposed criterion-based framework for compensation, we investigated 45 participants in three groups: (i) patients with mild cognitive impairment (MCI) and positive biomarkers indicative of Alzheimer’s disease (AD); (ii) cognitively normal young adults; (iii) cognitively normal older adults. To increase reliability, three sessions of resting-state functional magnetic resonance imaging for each participant were performed on different days (135 scans in total). To elucidate the dimensions and dynamics of resting-state compensatory mechanisms, we used graph theory analysis along with volumetric analysis. Graph theory analysis was applied based on the Brainnetome atlas, which provides a connectivity-based parcellation framework. Comprehensive neuropsychological examinations including the Rey Auditory Verbal Learning Test (RAVLT) and the Trail Making Test (TMT) were performed, to relate graph measures of compensatory nodes to cognition. To avoid false-positive findings, results were corrected for multiple comparisons. First, we observed an increase of degree centrality in cognition related brain regions of the middle frontal gyrus, precentral gyrus and superior parietal lobe despite local atrophy in MCI and healthy aging, indicating a resting-state connectivity increase with positive biomarkers. When relating the degree centrality measures to cognitive performance, we observed that greater connectivity led to better RAVLT and TMT scores in MCI and, hence, might constitute a compensatory mechanism. The detection and improved understanding of the compensatory dynamics in healthy aging and prodromal AD is mandatory for implementing and tailoring preventive interventions aiming at preserved overall cognitive functioning and delayed clinical onset of dementia.

Association of tau accumulation and atrophy in mild cognitive impairment: a longitudinal study.

To examine the patterns of longitudinal tau accumulation and cortical atrophy and their association in subjects with mild cognitive impairment (MCI). We collected 23 participants (60-89years old, 11 males/12 females) with MCI from the Alzheimer's Disease Neuroimaging Initiative database. All participants underwent 18F flortaucipir (FTP) positron emission tomography (PET) and structural magnetic resonance imaging (MRI) scans at the baseline and follow-up visits (12-36months). General linear models with covariates (baseline age, sex) were used to detect brain areas of significant tau accumulation and atrophy over time. Mediation analysis was employed to explore the potential reason for sequential biomarker changes in MCI progression, adjusting for baseline age, sex, and education level. Voxel-wise tau accumulation in MCI subjects was predominantly located in the inferior temporal cortex, middle temporal cortex, parietal cortex, posterior cingulate, precuneus, and temporoparietal regions (P < 0.001), and MRI atrophy included the inferior-middle temporal lobe, parietal lobe, and precuneus (P < 0.001). Longitudinal FTP accumulation was moderately associated with annualized MRI cortical atrophy (r = 0.409, 95% CI: 0.405-0.414, P < 0.01). Regional analyses indicated significant bivariate associations between annualized MRI cortical atrophy and FTP accumulation (baseline FTP cortical uptake and longitudinal FTP change). The results of the mediation analysis showed that the relationship between baseline FTP uptake and longitudinal cortical atrophy was partly mediated by the longitudinal FTP cortical change (indirect effect: 0.0107, P = 0.04). Our findings provide a preliminary description of the patterns of longitudinal FTP accumulation and annualized cortical atrophy in MCI progression, and MCI subjects with high tau binding levels show an increase risk of longitudinal tau accumulation, atrophy, and cognitive decline. Trial registration NCT00106899. Registered 1 April 2005, https://clinicaltrials.gov/ct2/show/study/NCT00106899.

Functional Characterization of Atrophy Patterns Related to Cognitive Impairment.

Introduction: Mild cognitive impairment (MCI) is a heterogenous syndrome considered as a risk factor for developing dementia. Previous work examining morphological brain changes in MCI has identified a temporo-parietal atrophy pattern that suggests a common neuroanatomical denominator of cognitive impairment. Using functional connectivity analyses of structurally affected regions in MCI, we aimed to investigate and characterize functional networks formed by these regions that appear to be particularly vulnerable to disease-related disruptions.Methods: Areas of convergent atrophy in MCI were derived from a quantitative meta-analysis and encompassed left and right medial temporal (i.e., hippocampus, amygdala), as well as parietal regions (precuneus), which were defined as seed regions for connectivity analyses. Both task-based meta-analytical connectivity modeling (MACM) based on the BrainMap database and task-free resting-state functional MRI in a large cohort of older adults from the 1000BRAINS study were applied. We additionally assessed behavioral characteristics associated with the seed regions using BrainMap meta-data and investigated correlations of resting-state connectivity with age.Results: The left temporal seed showed stronger associations with a fronto-temporal network, whereas the right temporal atrophy cluster was more linked to cortico-striatal regions. In accordance with this, behavioral analysis indicated an emphasis of the left temporal seed on language generation, and the right temporal seed was associated with the domains of emotion and attention. Task-independent co-activation was more pronounced in the parietal seed, which demonstrated stronger connectivity with a frontoparietal network and associations with introspection and social cognition. Correlation analysis revealed both decreasing and increasing functional connectivity with higher age that may add to pathological processes but also indicates compensatory mechanisms of functional reorganization with increasing age.Conclusion: Our findings provide an important pathophysiological link between morphological changes and the clinical relevance of major structural damage in MCI. Multimodal analysis of functional networks related to areas of MCI-typical atrophy may help to explain cognitive decline and behavioral alterations not tractable by a mere anatomical interpretation and therefore contribute to prognostic evaluations.

Effects of bilingualism on white matter atrophy in mild cognitive impairment: a diffusion tensor imaging study.

Previous investigations show that bilinguals exhibit the first symptoms of dementia 4-5years later than monolinguals. Therefore, bilingualism has been proposed as a cognitive reserve mechanism. Recent studies have advanced towards an understanding of the brain mechanisms underlying bilingualism's protection against dementia, but none of them deals with white matter (WM) diffusion. In this study, the topic was investigated by measuring WM integrity in a sample of 35 bilinguals and 53 passive bilinguals with mild cognitive impairment. No significant differences were found between the groups in cognitive level, education, age or sex. However, bilinguals showed higher mean diffusivity in the fornix, but higher fractional anisotropy, lower mean diffusivity, axial diffusivity and radial diffusivity in the parahippocampal cingulum, and lower radial diffusivity in the right uncinate fasciculus. Significant correlations were also found between WM integrity in the left parahippocampal cingulum and the Boston Naming Test in passive bilinguals. These results suggest that bilingualism contributes to a differential pattern of WM disintegration due to mild cognitive impairment in fibers related to bilingualism and memory.

The effect of white matter signal abnormalities on default mode network connectivity in mild cognitive impairment.

Regions within the default mode network (DMN) are particularly vulnerable to Alzheimer's disease pathology and mechanisms of DMN disruption in mild cognitive impairment (MCI) are still unclear. White matter lesions are presumed to be mechanistically linked to vascular dysfunction whereas cortical atrophy may be related to neurodegeneration. We examined associations between DMN seed‐based connectivity, white matter lesion load, and cortical atrophy in MCI and cognitively healthy controls. MCI showed decreased functional connectivity (FC) between the precuneus‐seed and bilateral lateral temporal cortex (LTC), medial prefrontal cortex (mPFC), posterior cingulate cortex, and inferior parietal lobe compared to those with controls. When controlling for white matter lesion volume, DMN connectivity differences between groups were diminished within bilateral LTC, although were significantly increased in the mPFC explained by significant regional associations between white matter lesion volume and DMN connectivity only in the MCI group. When controlling for cortical thickness, DMN FC was similarly decreased across both groups. These findings suggest that white matter lesions and cortical atrophy are differentially associated with alterations in FC patterns in MCI. Associations between white matter lesions and DMN connectivity in MCI further support at least a partial but important vascular contribution to age‐associated neural and cognitive impairment.

CORPUS CALLOSUM VOLUME AND EXECUTIVE FUNCTION: A POTENTIAL EARLY MARKER OF COGNITIVE DECLINE

Several lines of evidence suggest corpus callosum (CC) atrophy in mild cognitive impairment (MCI) and Alzheimer's Disease(AD). While MCI patients have anterior CC atrophy, AD patients have both anterior and posterior atrophy, suggesting progressive atrophy of CC in the course of AD. However, the relation between CC volume and cognitive measures in middle aged individuals without AD is not well-examined. Here, we therefore extend our earlier observations on the relation between CC regional volumes and executive functions in middle-aged individuals (50-65years). 61 healthy volunteers (female=31, age=64.09±8.06, years of education=16.90±4.00) participated in the Tata Longitudinal Study of Aging at Bangalore, India. Of these, a subset of 37 individuals were 50-65 years of age (female=21, age=58.56±4.21, years of education=17.02±4.52). All participants underwent neuropsychological testing and Magnetic Resonance Imaging (MRI) scans as per the Alzheimer's Disease Neuroimaging Initiative (ADNI) protocol. CC volumes were acquired for each individual using Freesurfer Software (http://surfer.nmr.mgh.harvard.edu/). Pearson's correlation analysis was conducted to examine the relation between CC volume and executive functions. Executive functions were tested using Controlled Oral Word Association Test (COWAT), digit span, Stroop test and Trail Making Test (TMT). At baseline (entire group), there was a significant positive correlation between COWAT-A score (higher the score, better the performance) and anterior CC-(r=0.561, p=0.001), central CC-(r=0.403,p=0.022) and posterior CC-(r=0.397,p=0.025) volumes. A significant negative correlation was seen between TMT-A Time (greater the time, poorer the performance) and mid-anterior CC-(r=-0.506,p=0.003), central CC-(r=-0.468,p=0.007), posterior CC-(r=-0.458,p=0.008), mid-posterior CC-(r=-0.424,p=0.016) and anterior CC-(r=-0.399,p=0.024) volumes; Stroop-B interference time and mid-posterior CC volume(r=-0.399,p=0.024); and Stroop-C interference time and mid-posterior CC-(r=-0.487,p=0.005), central CC-(r=-0.467,p=0.007), mid-anterior CC-(r=-0.409,p=0.020) and posterior CC-(r=-0.358,p=0.045) volumes. These findings are mirrored in the middle-aged subset, where there was a significant positive correlation between COWAT-A score and anterior CC-(r=0.558,p=0.007) and posterior CC-(r=0.479,p=0.024) volumes; and a significant negative correlation between TMT-A Time and mid-anterior CC-(r=-0.625,p=0.002), central CC-(r=-0.509,p=0.016), posterior CC-(r=-0.497,p=0.019) and anterior CC-(r=-0.469,p=0.028) volumes. Our findings indicate a significant association between CC volume and executive function. Findings suggest that those with lesser CC volume have lower executive function performance. These relationships observable in middle-age (50-65 years), indicate that CC atrophy is a potential early marker of cognitive decline. Longitudinal observations of these individuals will inform whether CC volumes are early markers of cognitive decline.

Plasma Tau Association with Brain Atrophy in Mild Cognitive Impairment and Alzheimer's Disease.

Peripheral (plasma) and central (cerebrospinal fluid, CSF) measures of tau are higher in Alzheimer's disease (AD) relative to prodromal stages and controls. While elevated CSF tau concentrations have been shown to be associated with lower grey matter density (GMD) in AD-specific regions, this correlation has yet to be examined for plasma in a large study. Determine the neuroanatomical correlates of plasma tau using voxel-based analysis. Cross-sectional data for 508 ADNI participants were collected for clinical, plasma total-tau (t-tau), CSF amyloid (Aβ42) and tau, and MRI variables. The relationship between plasma tau and GMD and between CSF t-tau and GMD were assessed on a voxel-by-voxel basis using regression models. Age, sex, APOEɛ4 status, diagnosis, and total intracranial volume were used as covariates where appropriate. Participants were defined as amyloid positive (Aβ+) if CSF Aβ42 was <192 pg/mL. Plasma tau was negatively correlated with GMD in the medial temporal lobe (MTL), precuneus, thalamus, and striatum. The associations with thalamus and striatum were independent of diagnosis. A negative correlation also existed between plasma tau and GMD in Aβ+ participants in the MTL, precuneus, and frontal lobe. When compared to CSF t-tau, plasma tau showed a notably different associated brain atrophy pattern, with only small overlapping regions in the fusiform gyrus. Plasma tau may serve as a non-specific marker for neurodegeneration but is still relevant to AD considering low GMD was associated with plasma tau in Aβ+ participants and not Aβ-participants.

Gender, apolipoprotein E genotype, and mesial temporal atrophy: 2-year follow-up in patients with stable mild cognitive impairment and with progression from mild cognitive impairment to Alzheimer's disease.

This study aimed to examine the relationship between gender, apolipoprotein E (APOE) genotype, and mesial temporal atrophy in mild cognitive impairment (MCI) with and without progression to Alzheimer's disease (AD). We evaluated 236 MCI patients with (n = 121) and without (n = 115) AD progression. Longitudinal MRI-based hippocampal volumes (HV) and entorhinal cortex (ERC) thickness were obtained. The Clinical Dementia Rating Sum of Boxes (CDR-SB) score was used to assess disease severity. We found a significant effect of APOE, gender, and clinical course (stable MCI versus MCI-AD progression) on HV. There was a significant effect of clinical course and APOE, but not gender, on ERC. Baseline HV and APOE4 status predicted MCI-AD progression in women. Baseline ERC and APOE4 status predicted MCI-AD progression in men. There were significant differences in CDR-SB scores between patients with and without MCI-AD progression, but not between males and females, or APOE4 carriers and non-carriers. HV, but not ERC, is strongly influenced by gender in MCI. The effects of gender and APOE4 on neuroimaging biomarkers have potentially important implications in the prediction of MCI-AD progression and should be taken into account in clinical trials.