scholarly journals The Relationship Between Anxiety and Incident Agitation in Alzheimer’s Disease

2020 ◽  
Vol 78 (3) ◽  
pp. 1119-1127
Author(s):  
Kathy Y. Liu ◽  
Harry Costello ◽  
Suzanne Reeves ◽  
Robert Howard ◽  
Keyword(s):  
Risk Factors ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Regression Models ◽  
Mixed Effects ◽  
Neuropsychiatric Symptom ◽  
Positive Linear Relationship ◽  
Potential Risk Factors ◽  
The Relationship

Background: Agitation in Alzheimer’s disease (AD) has been hypothesized to be an expression of anxiety, but whether anxiety early in the course of dementia could be a risk factor for developing later agitation is unknown. Objective: We used the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database to examine the longitudinal relationship between anxiety and incident agitation in individuals with a diagnosis of AD at baseline or during follow-up. Methods: Longitudinal neuropsychiatric symptom data from AD individuals who were agitation-free at study baseline (N = 272) were analyzed using mixed effects regression models to test the longitudinal relationship between baseline and incident anxiety with incident agitation. Results: Anxiety at baseline was not associated with subsequent agitation, but there was a positive linear relationship between incident anxiety and agitation over the study duration. Baseline apathy and delusions were consistently associated with subsequent agitation and greater disease severity and illness duration also appeared to be risk factors for agitation. Conclusion: Our findings support the concept that anxiety and agitation are likely to be distinct rather than equivalent constructs in mild-moderate AD. Future longitudinal cohort studies are needed to replicate these findings and further characterize potential risk factors for agitation, such as apathy and delusions.

Elucidating the risk factors for progression from amyloid-negative amnestic mild cognitive impairment to dementia

2020 ◽  
Vol 17 ◽  
Author(s):  
Hyung-Ji Kim ◽  
Jae-Hong Lee ◽  
E-nae Cheong ◽  
Sung-Eun Chung ◽  
Sungyang Jo ◽  
...  
Keyword(s):  
Risk Factors ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Amnestic Mild Cognitive Impairment ◽  
Amyloid Pet ◽  
Clinical Progression ◽  
Amnestic Mci

Background: Amyloid PET allows for the assessment of amyloid β status in the brain, distinguishing true Alzheimer’s disease from Alzheimer’s disease-mimicking conditions. Around 15–20% of patients with clinically probable Alzheimer’s disease have been found to have no significant Alzheimer’s pathology on amyloid PET. However, a limited number of studies had been conducted this subpopulation in terms of clinical progression. Objective: We investigated the risk factors that could affect the progression to dementia in patients with amyloid-negative amnestic mild cognitive impairment (MCI). Methods: This study was a single-institutional, retrospective cohort study of patients over the age of 50 with amyloidnegative amnestic MCI who visited the memory clinic of Asan Medical Center with a follow-up period of more than 36 months. All participants underwent brain magnetic resonance imaging (MRI), detailed neuropsychological testing, and fluorine-18[F18]-florbetaben amyloid PET. Results: During the follow-up period, 39 of 107 patients progressed to dementia from amnestic MCI. In comparison with the stationary group, the progressed group had a more severe impairment in verbal and visual episodic memory function and hippocampal atrophy, which showed an Alzheimer’s disease-like pattern despite the lack of evidence for significant Alzheimer’s disease pathology. Voxel-based morphometric MRI analysis revealed that the progressed group had a reduced gray matter volume in the bilateral cerebellar cortices, right temporal cortex, and bilateral insular cortices. Conclusion: Considering the lack of evidence of amyloid pathology, clinical progression of these subpopulation may be caused by other neuropathologies such as TDP-43, abnormal tau or alpha synuclein that lead to neurodegeneration independent of amyloid-driven pathway. Further prospective studies incorporating biomarkers of Alzheimer’s diseasemimicking dementia are warranted.

Abstract T P160: Influence of Polyunsaturated Fatty Acids on Cognition in Elderly Alzheimer's Disease Patients

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Takashi Yamazaki ◽  
Ken Nagata ◽  
Daiki Takano ◽  
Tetsuya Maeda
Keyword(s):  
Alzheimer’S Disease ◽  
Blood Pressure ◽  
Alzheimer's Disease ◽  
Cognitive Function ◽  
Mmse Score ◽  
Characteristic Curve ◽  
Follow Up Study ◽  
Cognitive Stability ◽  
The Relationship

Background: Many genes and environmental factors linked to Alzheimer’s disease (AD) risk affect lipid metabolism or the cardiovascular system, strongly implicating cerebrovascular and metabolic dysfunction in AD pathogenesis. Although some PUFAs may improve cognitive function in aging individuals, it is still unclear how different PUFAs influence AD neuropathology and cognitive function. Objective: To examine the influence of polyunsaturated fatty acid (PUFA) metabolism on AD-associated cognitive decline, we investigated the relationship between serum PUFA profile and neuropsychological test performance. Methods: Cognitive functioning in patients with probable AD (n = 174, mean age 77.6 years) was examined using the Mini-Mental State Exam (MMSE) and clock drawing test (CDT). Serum samples were obtained for PUFA profile, including the eicosapentaenoic acid/arachidonic acid (EPA/AA) ratio, and measurement of brain natriuretic peptide (BNP) concentration. In the follow-up study, 47 subjects repeated MMSE and CDT after 1 year, According to the second MMSE score, the subjects were divided into the following 2 groups: those with unchanged or improved MMSE score and those with lower MMSE score. A receiver operating characteristic curve was used to evaluate the relationship between the EPA/AA ratio and 1-year cognitive stability. Results: In the cross-sectional study, total MMSE score correlated positively with the EPA/AA ratio and systolic blood pressure (SBP), and negatively with age and diastolic blood pressure (DBP) (p < 0.05). In the follow-up study, the MMSE score was lower than baseline in 20 subjects, whereas it was improved or unchanged in 29 patients. The EPA/AA ratio in the stable group was significantly greater than that in the deteriorating group, suggesting an association between higher EPA/AA ratio and cognitive stability over 1 year. The EPA/AA ratio predicted stability of cognitive performance with a sensitivity of 66% and specificity of 70% (odds ratio = 4.43) when the cut-off was 0.67. Conclusion: Our results suggest that serum EPA concentration strongly influences cognitive performances in AD patients. The EPA/AA ratio was a sensitive indicator of cognitive stability in this patient group.

scholarly journals Using Drosophila to Identify Naturally-Occurring Modifiers of Alzheimer's Disease

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 641-642
Author(s):  
Adrienne Wang ◽  
Ming Yang ◽  
Cecilia Fitzgerald-Cook ◽  
Ben Harrison ◽  
Akimi Green ◽  
...  
Keyword(s):  
Risk Factors ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Late Onset ◽  
Enrichment Analysis ◽  
Model Organisms ◽  
Naturally Occurring ◽  
Small Effect Size ◽  
Forward Genetic Screens ◽  
Potential Risk Factors

Abstract Despite significant progress in identifying risk factors for late-onset Alzheimer’s Disease (LOAD), much of the variance in disease pathogenesis remains unexplained, likely due to the contribution of many genes of small effect size. Model organisms such as Drosophila Melanogaster exhibit conservation in both disease-causing genes and cellular processes implicated in Alzheimer’s Disease (AD), offering a genetically tractable model that can be statistically leveraged to identify causal variants. Here, we combine a Drosophila model of AD with the Drosophila Genetic Reference Panel (DGRP), a model of natural variation consisting of over 200 fully sequenced, isogenic lines derived from a wild-caught population. Expression of two proteins closely associated with AD pathogenesis, A□42 and Tau, in the Drosophila eye results in a “rough eye” phenotype, an easily quantifiable phenotype caused by degeneration of the ommatidial array. By quantifying the degree of A□42- and Tau-mediated degeneration across 164 lines of the DGRP and using a gene-based approach to map associations, we have identified and validated a subset of naturally occurring modifiers of degeneration in Drosophila. Enrichment analysis reveals that the set of genes identified in our screen show significant enrichment for genes identified as significant or suggestive (4x10-6&gt;p&gt;2x10-11) in human GWAS studies. The results presented here provide proof-of-principal for an approach that combines the strengths of forward genetic screens in model organisms with the power of human GWAS studies to identify and validate potential risk factors that have been difficult to detect in human studies alone.

The relationship between Alzheimer's disease and vascular risk factors

2020 ◽  
Vol 34 (S1) ◽  
pp. 1-1
Author(s):  
Xianghui Chen ◽  
Weidong Zhang ◽  
Xiaohong Qiao ◽  
Youliang Li ◽  
Hubin Duan ◽  
...  
Keyword(s):  
Risk Factors ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Vascular Risk Factors ◽  
Vascular Risk ◽  
The Relationship

scholarly journals Factors Associated with Lumbar Puncture Participation in Alzheimer’s Disease Research

2020 ◽  
Vol 77 (4) ◽  
pp. 1559-1567
Author(s):  
Madeleine M. Blazel ◽  
Karen K. Lazar ◽  
Carol A. Van Hulle ◽  
Yue Ma ◽  
Aleshia Cole ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Adverse Events ◽  
Important Predictor ◽  
Parental History ◽  
Factors Associated ◽  
Disease Research ◽  
Relationship Of ◽  
The Relationship

Background: Cerebrospinal fluid (CSF) provides insight into the spectrum of Alzheimer’s disease (AD) pathology. While lumbar punctures (LPs) for CSF collection are generally considered safe procedures, many participants remain hesitant to participate in research involving LPs. Objective: To explore factors associated with participant willingness to undergo a research LP at baseline and follow-up research study visit. Methods: We analyzed data from 700 participants with varying cognition (unimpaired, mild cognitive impairment, and dementia) in the Wisconsin Alzheimer’s Disease Research Center. We evaluated the relationship of demographic variables (age, sex, race, ethnicity, and years of education) and clinical variables (waist-to-hip ratio, body mass index, AD parental history, cognitive diagnosis) on decision to undergo baseline LP1. We evaluated the relationship of prior LP1 experience (procedure success and adverse events) with the decision to undergo follow-up LP2. The strongest predictors were incorporated into regression models. Results: Over half of eligible participants opted into both baseline and follow-up LP. Participants who underwent LP1 had higher mean education than those who declined (p = 0.020). White participants were more likely to choose to undergo LP1 (p < 0.001); 33% of African American participants opted in compared to 65% of white participants. Controlling for age, education, and AD parental history, race was the only significant predictor for LP1 participation. Controlling for LP1 mild adverse events, successful LP1 predicted LP2 participation. Conclusion: Race was the most important predictor of baseline LP participation, and successful prior LP was the most important predictor of follow-up LP participation.

scholarly journals Risk Factors That Affect Life Expectancy in Alzheimer's Disease: A 15-Year Follow-Up

2014 ◽  
Vol 38 (5-6) ◽  
pp. 286-299 ◽  
Author(s):  
Carina Wattmo ◽  
Elisabet Londos ◽  
Lennart Minthon
Keyword(s):  
Risk Factors ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Life Expectancy

scholarly journals Modifiable risk factors moderate the relationship between beta-amyloid and cognition in midlife

2017 ◽  
Author(s):  
Lindsay R. Clark ◽  
Rebecca L. Koscik ◽  
Samantha L. Allison ◽  
Sara E. Berman ◽  
Cynthia M. Carlsson ◽  
...  
Keyword(s):  
Risk Factors ◽  
Alzheimer’S Disease ◽  
Blood Pressure ◽  
Alzheimer's Disease ◽  
Depressive Symptoms ◽  
Verbal Learning ◽  
Beta Amyloid ◽  
Modifiable Risk Factors ◽  
Pittsburgh Compound B ◽  
The Relationship

ABSTRACTAlthough evidence suggests a relationship between elevated beta-amyloid and cognitive decline, approximately 30% of older adults with positive markers of amyloid remain cognitively healthy. Our objective was to test if the presence of modifiable risk factors (i.e., central obesity, hypertension, and depressive symptoms) moderated the relationship between amyloid and longitudinal cognitive performance. Data were from 207 adults (140 females; age range=40-70) enriched for Alzheimer’s disease risk (73% parental history of Alzheimer’s disease) enrolled in the Wisconsin Registry for Alzheimer’s Prevention study. Participants completed at least three neuropsychological evaluations and one biomarker visit ([C11]Pittsburgh Compound B PET scan or lumbar puncture). Participants were characterized as high or low on beta-amyloid using cutoffs developed for [C11]Pittsburgh Compound B-PET distribution volume ratio or CSF amyloid beta 1-42 values. Participants were also coded as high or low risk on obesity (waist circumference > 102 cm for males or 88 cm for females), hypertension (systolic blood pressure ≥ 140 mm Hg or diastolic blood pressure ≥ 90 mm Hg), and depressive symptoms (Center for Epidemiologic Studies of Depression scale ≥ 16). Linear mixed effects regression models examined three-way interactions between modifiable risk factor status x beta-amyloid status x visit age on longitudinal Verbal Learning & Memory and Speed & Flexibility factor scores. Results indicated that the relationship between beta-amyloid and Verbal Learning & Memory decline was moderated by the presence of hypertension at baseline (p = .02), presence of hypertension at all visits (p = .001), and presence of obesity at all visits (p = .049). Depressive symptoms did not moderate the association between beta-amyloid and longitudinal Verbal Learning & Memory (p = .62) or Speed & Flexibility (p = .15) performances. In this at-risk for Alzheimer’s disease cohort, modifiable risk factors of hypertension and obesity moderated the relationship between beta-amyloid and cognitive decline. Identification and modification of these risk factors in late middle age may slow the effect of amyloid on the progression of cognitive symptoms.

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