Abstract 44: Associations of Atrial Fibrillation, Neuroimaging Measures of Cerebrovascular Disease and Alzheimer’S Disease-related Pathology, and Cognitive Impairment

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Jonathan Graff-Radford ◽  
Rosebud Roberts ◽  
Malini Madhavan ◽  
Alejandro Rabinstein ◽  
Ruth Cha ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
White Matter ◽  
Cerebrovascular Disease ◽  
Regression Models ◽  
Grey Matter ◽  
White Matter Hyperintensity ◽  
Carrier Status

The objective of this study was to investigate the cross-sectional associations of atrial fibrillation with neuroimaging measures of cerebrovascular disease and Alzheimer’s disease-related pathology, and their interaction with cognitive impairment. MRI scans of non-demented individuals (n=1044) from the population-based Mayo Clinic Study of Aging were analyzed for infarctions, total grey matter, hippocampal and white matter hyperintensity volumes. A subset of 496 individuals underwent FDG and C-11 Pittsburgh compound B (PiB) PET scans. We assessed the associations of atrial fibrillation with i) categorical MRI measures (cortical and subcortical infarctions) using multivariable logistic regression models, and with ii) continuous MRI measures ( hippocampal, total grey matter, and white matter hyperintensity volumes) and FDG-PET and PiB-PET measures using multivariable linear regression models, and adjusting for confounders. Among participants who underwent MRI (median age, 77.8, 51.6% male), 13.5% had atrial fibrillation. Presence of atrial fibrillation was associated with subcortical infarctions (odds ratio [OR], 1.83; p=0.002), cortical infarctions (OR, 1.91; p=0.03), total grey matter volume (Beta [β], -.025, p<.0001) after controlling for age, education, gender, APOE e4 carrier status, coronary artery disease, diabetes, history of clinical stroke, and hypertension. However, atrial fibrillation was not associated with white matter hyperintensity volume, hippocampal volume, Alzheimer’s pattern of FDG hypometabolism or PiB uptake. There was a significant interaction of cortical infarction (p for interaction=0.004) and subcortical infarction (p for interaction =0.015) with atrial fibrillation with regards to odds of mild cognitive impairment (MCI). Using subjects with no atrial fibrillation and no infarction as the reference, the OR (95% confidence intervals [CI]) for MCI was 2.98 (1.66, 5.35;p = 0.0002) among participants with atrial fibrillation and any infarction, 0.69 (0.36, 1.33;p= 0.27) for atrial fibrillation and no infarction, and 1.50 (0.96, 2.32;p = 0.07) for no atrial fibrillation and any infarction. These data highlight that atrial fibrillation is associated with MCI in the presence of infarctions.

scholarly journals White matter hyperintensities and neuropsychiatric symptoms in Alzheimer’s disease and mild cognitive impairment

2019 ◽  
Author(s):  
Karen Misquitta ◽  
Mahsa Dadar ◽  
D. Louis Collins ◽  
Maria Carmela Tartaglia ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
White Matter ◽  
Cerebrovascular Disease ◽  
Grey Matter ◽  
White Matter Hyperintensities ◽  
Neuropsychiatric Symptoms ◽  
Grey Matter Atrophy

AbstractBackground and Purpose: Neuropsychiatric symptoms (NPS) are frequently encountered in patients with Alzheimer’s disease (AD). Focal grey matter atrophy has been linked to NPS development. Cerebrovascular disease can cause focal lesions and is common among AD patients. As cerebrovascular disease can be detected on MRI as white matter hyperintensities (WMH), this study evaluated WMH burden in mild cognitive impairment (MCI), AD and normal controls and determined their relationship with NPS. Methods: NPS were assessed using the Neuropsychiatric Inventory and grouped into subsyndromes. WMH were measured using an automatic segmentation technique and mean deformation-based morphometry was used to measure atrophy of grey matter regions. Results: WMHs and grey matter atrophy both contributed significantly to NPS subsyndromes in MCI and AD subjects, however, WMH burden played a greater role. Conclusions: This study could provide a better understanding of the pathophysiology of NPS in AD.

scholarly journals Intranasal Insulin Reduces White Matter Hyperintensity Progression in Association with Improvements in Cognition and CSF Biomarker Profiles in Mild Cognitive Impairment and Alzheimer’s Disease

2021 ◽  
pp. 1-9
Author(s):  
D. Kellar ◽  
S.N. Lockhart ◽  
P. Aisen ◽  
R. Raman ◽  
R.A. Rissman ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
White Matter ◽  
Cerebral Spinal Fluid ◽  
Spinal Fluid ◽  
White Matter Hyperintensity ◽  
Intranasal Insulin ◽  
Fluid Biomarker

Background: Intranasally administered insulin has shown promise in both rodent and human studies in Alzheimer’s disease; however, both effects and mechanisms require elucidation. Objective: We assessed the effects of intranasally administered insulin on white matter health and its association with cognition and cerebral spinal fluid biomarker profiles in adults with mild cognitive impairment or Alzheimer’s disease in secondary analyses from a prior phase 2 clinical trial (NCT01767909). Design: A randomized (1:1) double-blind clinical trial. Setting: Twelve sites across the United States. Participants: Adults with mild cognitive impairment or Alzheimer’s disease. Intervention: Participants received either twice daily placebo or insulin (20 IU Humulin R U-100 b.i.d.) intranasally for 12 months. Seventy-eight participants were screened, of whom 49 (32 men) were enrolled. Measurements: Changes from baseline in global and regional white matter hyperintensity volume and gray matter volume were analyzed and related to changes in cerebral spinal fluid biomarkers, Alzheimer’s Disease Assessment Scale-Cognition, Clinical Disease Rating-Sum of Boxes, Alzheimer’s Disease Cooperative Study–Activities of Daily Living Scale, and a memory composite. Results: The insulin-treated group demonstrated significantly reduced changes in white matter hyperintensity volume in deep and frontal regions after 12 months, with a similar trend for global volume. White matter hyperintensity volume progression correlated with worsened Alzheimer’s disease cerebral spinal fluid biomarker profile and cognitive function; however, patterns of correlations differed by treatment group. Conclusion: Intranasal insulin treatment for 12 months reduced white matter hyperintensity volume progression and supports insulin’s potential as a therapeutic option for Alzheimer’s disease.

scholarly journals Cerebrovascular disease promotes tau pathology in Alzheimer’s disease

2020 ◽  
Vol 2 (2) ◽  
Author(s):  
Krystal K Laing ◽  
Sabrina Simoes ◽  
Gloria P Baena-Caldas ◽  
Patrick J Lao ◽  
Milankumar Kothiya ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
White Matter ◽  
Cerebrovascular Disease ◽  
Cerebral Artery ◽  
White Matter Hyperintensities ◽  
Artery Occlusion ◽  
White Matter Hyperintensity ◽  
Tau Pathology ◽  
Cerebral Artery Occlusion

Abstract Small vessel cerebrovascular disease, visualized as white matter hyperintensities on T2-weighted magnetic resonance imaging, contributes to the clinical presentation of Alzheimer’s disease. However, the extent to which cerebrovascular disease represents an independent pathognomonic feature of Alzheimer's disease or directly promotes Alzheimer’s pathology is unclear. The purpose of this study was to examine the association between white matter hyperintensities and plasma levels of tau and to determine if white matter hyperintensities and tau levels interact to predict Alzheimer’s disease diagnosis. To confirm that cerebrovascular disease promotes tau pathology, we examined tau fluid biomarker concentrations and pathology in a mouse model of ischaemic injury. Three hundred ninety-one participants from the Alzheimer’s Disease Neuroimaging Initiative (74.5 ± 7.1 years of age) were included in this cross-sectional analysis. Participants had measurements of plasma total-tau, cerebrospinal fluid beta-amyloid, and white matter hyperintensities, and were diagnosed clinically as Alzheimer’s disease (n = 97), mild cognitive impairment (n = 186) or cognitively normal control (n = 108). We tested the relationship between plasma tau concentration and white matter hyperintensity volume across diagnostic groups. We also examined the extent to which white matter hyperintensity volume, plasma tau, amyloid positivity status and the interaction between white matter hyperintensities and plasma tau correctly classifies diagnostic category. Increased white matter hyperintensity volume was associated with higher plasma tau concentration, particularly among those diagnosed clinically with Alzheimer’s disease. Presence of brain amyloid and the interaction between plasma tau and white matter hyperintensity volume distinguished Alzheimer’s disease and mild cognitive impairment participants from controls with 77.6% and 63.3% accuracy, respectively. In 63 Alzheimer’s Disease Neuroimaging Initiative participants who came to autopsy (82.33 ± 7.18 age at death), we found that higher degrees of arteriosclerosis were associated with higher Braak staging, indicating a positive relationship between cerebrovascular disease and neurofibrillary pathology. In a transient middle cerebral artery occlusion mouse model, aged mice that received transient middle cerebral artery occlusion, but not sham surgery, had increased plasma and cerebrospinal fluid tau concentrations, induced myelin loss, and hyperphosphorylated tau pathology in the ipsilateral hippocampus and cerebral hemisphere. These findings demonstrate a relationship between cerebrovascular disease, operationalized as white matter hyperintensities, and tau levels, indexed in the plasma, suggesting that hypoperfusive injury promotes tau pathology. This potential causal association is supported by the demonstration that transient cerebral artery occlusion induces white matter damage, increases biofluidic markers of tau, and promotes cerebral tau hyperphosphorylation in older-adult mice.

A-4 Amyloid Status Modifies the Association between Subjective Cognitive Decline and Brain MRI Metrics

2021 ◽  
Vol 36 (6) ◽  
pp. 1025-1025
Author(s):  
Marilyn J Steinbach ◽  
Omair A Khan ◽  
Dandan Liu ◽  
Camdyn Gilbert ◽  
Natalie Thwaites ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
White Matter ◽  
Cerebrovascular Disease ◽  
Cognitive Decline ◽  
Brain Mri ◽  
Ventricular Volume ◽  
White Matter Hyperintensity ◽  
Subjective Cognitive Decline ◽  
The Impact

Abstract Objective Subjective cognitive decline (SCD), a potential precursor to Alzheimer’s disease (ad), has been associated with increased neurodegeneration and cerebrovascular disease longitudinally. However, the impact of amyloid status, an early pathological marker of Alzheimer’s disease (ad) on these longitudinal associations is less clear. Here, we related baseline SCD to longitudinal biomarkers of brain health in the context of amyloid status. Method Participants included 139 non-demented older adults (72 ± 7 years) from the Vanderbilt Memory & Aging Project who completed a SCD questionnaire and fasting lumbar-puncture to quantify amyloid status (defined using published cutoffs of amyloid-beta42 levels) at baseline. 3 T brain-MRI to measure gray and white matter hyperintensity (WMH) volumes was collected at baseline, 18-months, 3-years, and 5-years. Linear mixed effects models assessed if baseline SCD X amyloid status was associated with longitudinal total and lobar grey and white matter volumes, covarying for baseline age, sex, race/ethnicity, education, diagnosis, mood, and apolipoprotein-Ee4 status. Models were also stratified by baseline amyloid status. Results Baseline SCD score and amyloid status interacted with total gray (p = 0.02) and WMH volume (p &lt; 0.05). In stratified models, higher total SCD predicted increased inferior lateral ventricular volume (p &lt; 0.001) among amyloid positive individuals. Conversely, in amyloid negative, greater baseline SCD was associated with increased WMH volumes globally (p = 0.03) and in the frontal and parietal lobes (p-values &lt;0.035). Conclusion In the presence of amyloid, the presence of SCD is predictive of neurodegeneration in ad-specific regions. Conversely, SCD without amyloidosis may reflect a cerebrovascular disease, indicated by WMHs. Results highlight how amyloid status may help delineate etiologies of SCD.

scholarly journals Cerebral Amyloid Angiopathy Is Associated With Emotional Dysregulation, Impulse Dyscontrol, and Apathy

2021 ◽  
Author(s):  
Eric E. Smith ◽  
Stephanie Crites ◽  
Meng Wang ◽  
Anna Charlton ◽  
Angela Zwiers ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
White Matter ◽  
Linear Regression ◽  
White Matter Hyperintensity ◽  
Amyloid Angiopathy ◽  
Cerebral Amyloid ◽  
Normal Cognition

Background Cerebral amyloid angiopathy (CAA) causes cognitive decline, but it is not known whether it is associated with neuropsychiatric symptoms (NPS). Methods and Results Participants with CAA, mild cognitive impairment, mild dementia due to Alzheimer's disease, and normal cognition were recruited from stroke and dementia clinics and community advertising. NPS were captured using the Neuropsychiatric Inventory Questionnaire short form. The number and total severity (number multiplied by severity of each symptom [mild, moderate, or severe]) of NPS were analyzed using generalized linear regression with a negative binomial link and multiple linear regression, adjusting for age, sex, and education. A total of 109 participants (43 with CAA, 15 with Alzheimer's disease, 28 with mild cognitive impairment, and 23 with normal cognition) (mean age 71.1 [SD=7.6]; 53.2% male) were included. The most frequent NPS in CAA were depression/dysphoria (48.8%), irritability/lability (37.2%), agitation/aggression (37.2%), apathy/indifference (34.9%), and anxiety (32.6%). In adjusted models, patients with CAA had 3.2 times (95% CI, 1.7–6.0) more NPS symptoms and 3.1 units (95% CI, 1.0–5.1) higher expected severity score. The number of NPS was similar to patients with mild cognitive impairment (3.2 times higher than controls) but less than in patients with Alzheimer's disease dementia (4.1 times higher than controls). Within patients with CAA, there were 1.20 times (95% CI, 1.01–1.32) more NPS per 1% increase in white matter hyperintensity as a percentage of intracranial volume. Conclusions NPS are common in CAA, with a similar prevalence as in mild cognitive impairment. The association of the total number of NPS with higher white matter hyperintensity volume suggests that white matter damage may underlie some of these symptoms.

scholarly journals Symptom profiles in patients with Alzheimer’s disease with and without concomitant cerebrovascular disease: an observational study

2019 ◽  
Author(s):  
Rannveig Sakshaug Eldholm ◽  
Maria Lage Barca ◽  
Karin Persson ◽  
Anne-Brita Knapskog ◽  
Knut Engedal ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Executive Function ◽  
Depressive Symptoms ◽  
White Matter ◽  
Cerebrovascular Disease ◽  
White Matter Hyperintensities ◽  
Cognitive Test ◽  
Age And Sex

Abstract Background: Diagnostic criteria of Alzheimer’s disease (AD) and vascular cognitive impairment (VCI) describe different cognitive profiles. AD patients often have concomitant cerebrovascular disease (CVD) and these patients could therefore be expected to display symptoms of both AD and VCI. AD patients with concomitant CVD display symptoms of cognitive impairment with less AD pathology than those without CVD. Medial temporal atrophy (MTA) on magnetic resonance imaging (MRI) is a biomarker of neurodegeneration in AD, and we would expect less MTA in AD patients with CVD. The first aim was to examine whether there were differences in the results of cognitive tests for memory, executive function, and processing speed, or in depressive symptoms, between AD patients with and without CVD. Secondly, to assess whether MTA on MRI is more pronounced among AD patients without CVD. Methods: A total of 192 AD patients with amnestic mild cognitive impairment or mild dementia underwent cognitive assessment and depression screening. Cerebral MRIs were assessed for MTA, white matter hyperintensities, and lacunar and cortical infarcts. CVD was defined as the presence of white matter hyperintensities Fazekas scale ≥2 or any infarct. To study the effect of CVD, several multiple linear regression analyses were carried out using CVD adjusted for age and sex as the independent variable, and cognitive test scores, depression scores, and MTA as dependent variables. Results: Mean age was 72.2 (SD 8.3) years. The number of AD patients with and without concomitant CVD was 121 and 71, respectively. The group with CVD scored significantly lower on tests of attention, executive function and immediate recall compared with the group without CVD. In analyses controlled for age and sex, concomitant CVD was not associated with significant differences in any cognitive test nor in depressive symptoms. A statistically significant association between AD with concomitant CVD and more pronounced MTA was identified. Conclusions: The results indicate that cognitive test profiles, depressive symptoms, and MTA scores cannot be used to distinguish AD patients with and without CVD.

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