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 Hippocampal Functional Connectivity and Memory Performance After Exercise Intervention in Older Adults with Mild Cognitive Impairment

2021 ◽  
pp. 1-17
Author(s):  
Junyeon Won ◽  
Daniel D. Callow ◽  
Gabriel S. Pena ◽  
Leslie S. Jordan ◽  
Naomi A. Arnold-Nedimala ◽  
...  
Keyword(s):  
Older Adults ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Functional Connectivity ◽  
Memory Performance ◽  
Verbal Learning ◽  
Memory Task ◽  
Control Group ◽  
Age Related ◽  
Lm Test

Background: Exercise training (ET) has neuroprotective effects in the hippocampus, a key brain region for memory that is vulnerable to age-related dysfunction. Objective: We investigated the effects of ET on functional connectivity (FC) of the hippocampus in older adults with mild cognitive impairment (MCI) and a cognitively normal (CN) control group. We also assessed whether the ET-induced changes in hippocampal FC (Δhippocampal-FC) are associated with changes in memory task performance (Δmemory performance). Methods: 32 older adults (77.0±7.6 years; 16 MCI and 16 CN) participated in the present study. Cardiorespiratory fitness tests, memory tasks (Rey Auditory Verbal Learning Test (RAVLT) and Logical Memory Test (LM)), and resting-state fMRI were administered before and after a 12-week walking ET intervention. We utilized a seed-based correlation analysis using the bilateral anterior and posterior hippocampi as priori seed regions of interest. The associations of residualized ET-induced Δhippocampal-FC and Δmemory performance were assessed using linear regression. Results: There were significant improvements in RAVLT Trial 1 and LM test performance after ET across participants. At baseline, MCI, compared to CN, demonstrated significantly lower posterior hippocampal FC. ET was associated with increased hippocampal FC across groups. Greater ET-related anterior and posterior hippocampal FC with right posterior cingulate were associated with improved LM recognition performance in MCI participants. Conclusion: Our findings indicate that hippocampal FC is significantly increased following 12-weeks of ET in older adults and, moreover, suggest that increased hippocampal FC may reflect neural network plasticity associated with ET-related improvements in memory performance in individuals diagnosed with MCI.

scholarly journals Memory-Related Frontal Brainwaves Predict Transition to Mild Cognitive Impairment in Healthy Older Individuals Five Years Before Diagnosis

2020 ◽  
pp. 1-11
Author(s):  
Yang Jiang ◽  
Juan Li ◽  
Frederick A. Schmitt ◽  
Gregory A. Jicha ◽  
Nancy B. Munro ◽  
...  
Keyword(s):  
Older Adults ◽  
Working Memory ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Memory Performance ◽  
Memory Task ◽  
Cognitive Status ◽  
Older Individuals ◽  
Increased Risk ◽  
Differentiation Pattern

Background: Early prognosis of high-risk older adults for amnestic mild cognitive impairment (aMCI), using noninvasive and sensitive neuromarkers, is key for early prevention of Alzheimer’s disease. We have developed individualized measures in electrophysiological brain signals during working memory that distinguish patients with aMCI from age-matched cognitively intact older individuals. Objective: Here we test longitudinally the prognosis of the baseline neuromarkers for aMCI risk. We hypothesized that the older individuals diagnosed with incident aMCI already have aMCI-like brain signatures years before diagnosis. Methods: Electroencephalogram (EEG) and memory performance were recorded during a working memory task at baseline. The individualized baseline neuromarkers, annual cognitive status, and longitudinal changes in memory recall scores up to 10 years were analyzed. Results: Seven of the 19 cognitively normal older adults were diagnosed with incident aMCI for a median 5.2 years later. The seven converters’ frontal brainwaves were statistically identical to those patients with diagnosed aMCI (n = 14) at baseline. Importantly, the converters’ baseline memory-related brainwaves (reduced mean frontal responses to memory targets) were significantly different from those who remained normal. Furthermore, differentiation pattern of left frontal memory-related responses (targets versus nontargets) was associated with an increased risk hazard of aMCI (HR = 1.47, 95% CI 1.03, 2.08). Conclusion: The memory-related neuromarkers detect MCI-like brain signatures about five years before diagnosis. The individualized frontal neuromarkers index increased MCI risk at baseline. These noninvasive neuromarkers during our Bluegrass memory task have great potential to be used repeatedly for individualized prognosis of MCI risk and progression before clinical diagnosis.

White matter diffusivity predicts memory in patients with subjective and mild cognitive impairment and normal CSF total tau levels

2009 ◽  
Vol 16 (1) ◽  
pp. 58-69 ◽  
Author(s):  
RAMUNE GRAMBAITE ◽  
VIDAR STENSET ◽  
IVAR REINVANG ◽  
KRISTINE B. WALHOVD ◽  
ANDERS M. FJELL ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
White Matter ◽  
Diffusion Tensor ◽  
Memory Performance ◽  
Neuropsychological Test ◽  
Verbal Learning ◽  
Tau Pathology ◽  
Total Tau ◽  
T Tau

AbstractSubjective and mild cognitive impairment (SCI and MCI) are etiologically heterogeneous conditions. This poses problems for assessment of pathophysiological mechanisms and risk of conversion to dementia. Neuropsychological, imaging, and cerebrospinal fluid (CSF) findings serve to distinguish Alzheimer’s disease (AD) and other etiological subgroups. Tau-molecules stabilize axonal microtubuli; high CSF total tau (T-tau) reflects ongoing axonal damage consistent with AD. Here, we stratify patients by CSF T-tau pathology to determine if memory network diffusion tensor imaging (DTI) predicts memory performance in the absence of elevated T-tau. We analyzed neuropsychological test results, hippocampus volume (HcV) and white matter diffusivity in 45 patients (35 with normal T-tau). The T-tau pathology group showed more hippocampus atrophy and memory impairment than the normal T-tau group. In the T-tau normal group: (1) memory was related with white matter diffusivity [fractional anisotropy (FA) and radial diffusivity (DR)], and (2) FA of the genu corpus callosum was a unique predictor of variance for verbal learning, and HcV did not contribute to this prediction. The smaller sample size in the T-tau pathology group precludes firm conclusions. In the normal T-tau group, white matter tract and memory changes may be associated with normal aging, or with non-tau related pathological mechanisms. (JINS, 2010,16, 58–69.)

scholarly journals Accelerometer Physical Activity is Associated with Greater Gray Matter Volumes in Older Adults Without Dementia or Mild Cognitive Impairment

2018 ◽  
Vol 74 (7) ◽  
pp. 1142-1151 ◽  
Author(s):  
Shannon Halloway ◽  
Konstantinos Arfanakis ◽  
JoEllen Wilbur ◽  
Michael E Schoeny ◽  
Susan J Pressler
Keyword(s):  
Physical Activity ◽  
Older Adults ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Cognitive Function ◽  
Gray Matter ◽  
Cross Sectional ◽  
Gray Matter Atrophy ◽  
Age Related ◽  
Gray Matter Volumes

Abstract Objectives Physical activity (PA) is a modifiable health behavior that can protect against age-related gray matter atrophy and cognitive dysfunction. Current studies of PA and gray matter failed to utilize device measures of PA and do not focus on adults >80 years. Thus, the purpose of this secondary analysis was to examine cross-sectional associations between accelerometer lifestyle PA and (a) gray matter volumes and (b) cognitive function, controlling for demographics, and health status. Method Participants were 262 older adults without dementia or mild cognitive impairment from Rush Memory and Aging Project, an epidemiological cohort study. Participants wore an accelerometer to assess total daily lifestyle PA, and completed anatomical magnetic resonance imaging to assess gray matter volumes and a neurocognitive test battery to assess cognitive function. Results Multivariate linear regression indicated that higher levels of total daily lifestyle PA was significantly related to larger gray matter volumes, F(2, 215) = 3.61, p = .027, including subcortical gray matter (β = 0.17, p = .007) and total gray matter (β = 0.11, p = .049), with no significant associations between lifestyle PA and cognitive function. Discussion These findings may inform future lifestyle PA interventions in order to attenuate age-related gray matter atrophy.

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