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 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.

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.

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