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 ◽  
...  

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.

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 161-162
Author(s):  
Yang An ◽  
Jennifer Schrack ◽  
Pei-Lun Kuo ◽  
Amal Wanigatunga ◽  
Eleanor Simonsick ◽  
...  

Abstract Older adults with slow gait have a modestly elevated risk of Alzheimer’s disease (AD). Whether strategies to maintain function, such as interlacing periods of activity and rest, modify this relationship is unknown. We analyzed 577 initially cognitively normal participants aged 50+(53%women,26%Black) who had baseline data on gait speed and fractionation via ActiHeart. Diagnoses of mild cognitive impairment (MCI)/AD were adjudicated during an average 7.3years follow-up. We examined gait speed, fractionation, and their interaction with MCI/AD risk using Cox proportional-hazards models, adjusted for demographics and APOE-e4. Each 0.2m/sec faster gait speed was associated with 24% lower risk of MCI/AD(p=0.04). Fractionation was not associated with MCI/AD risk(p&gt;0.05). There was a significant gait*fractionation interaction(p=0.013). At high fractionation, gait was not predictive of MCI/AD. Slow gait speed is less predictive of future MCI/AD in individuals who fractionate their activity to maintain function, possibly indicating brain function that drives such compensatory strategy is still conserved.


2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Tengfei Guo ◽  
Susan M. Landau ◽  
William J. Jagust ◽  

Abstract Background We recently reported that CSF phosphorylated tau (p-Tau181) relative to Aβ40 (CSF p-Tau/Aβ40 ratio) was less noisy and increased associations with Alzheimer’s disease (AD) biomarkers compared to CSF p-Tau181 alone. While elevations of CSF p-Tau/Aβ40 can occur in amyloid-β (Aβ) negative (Aβ-) individuals, the factors associated with these elevations and their role in neurodegeneration and cognitive decline are unknown. We aim to explore factors associated with elevated tau in CSF, and how these elevated tau are related to neurodegeneration and cognitive decline in the absence of Aβ positivity. Methods We examined relationships between CSF p-Tau/Aβ40, and CSF Aβ42/Aβ40, Aβ PET, and white matter hyperintensities (WMH) as well as vascular risk factors in 149 cognitively unimpaired and 52 impaired individuals who were presumably not on the Alzheimer’s disease (AD) pathway due to negative Aβ status on both CSF and PET. Subgroups had 18F-fluorodeoxyglucose (FDG) PET and adjusted hippocampal volume (aHCV), and longitudinal measures of CSF, aHCV, FDG PET, and cognition data, so we examined CSF p-Tau/Aβ40 associations with these measures as well. Results Elevated CSF p-Tau/Aβ40 was associated with older age, male sex, greater WMH, and hypertension as well as a pattern of hippocampal atrophy and temporoparietal hypometabolism characteristic of AD. Lower CSF Aβ42/Aβ40, higher WMH, and hypertension but not age, sex, Aβ PET, APOE-ε4 status, body mass index, smoking, and hyperlipidemia at baseline predicted CSF p-Tau/Aβ40 increases over approximately 5 years of follow-up. The relationship between CSF p-Tau/Aβ40 and subsequent cognitive decline was partially or fully explained by neurodegenerative measurements. Conclusions These data provide surprising clues as to the etiology and significance of tau pathology in the absence of Aβ. It seems likely that, in addition to age, both cerebrovascular disease and subthreshold levels of Aβ are related to this tau accumulation. Crucially, this phenotype of CSF tau elevation in amyloid-negative individuals share features with AD such as a pattern of metabolic decline and regional brain atrophy.


Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Takashi Yamazaki ◽  
Ken Nagata ◽  
Daiki Takano ◽  
Tetsuya Maeda

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.


Nutrients ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 206 ◽  
Author(s):  
Reale ◽  
Costantini ◽  
Jagarlapoodi ◽  
Khan ◽  
Belwal ◽  
...  

Background: Alzheimer’s disease (AD), the most threatening neurodegenerative disease, is characterized by the loss of memory and language function, an unbalanced perception of space, and other cognitive and physical manifestations. The pathology of AD is characterized by neuronal loss and the extensive distribution of senile plaques and neurofibrillary tangles (NFTs). The role of environment and the diet in AD is being actively studied, and nutrition is one of the main factors playing a prominent role in the prevention of neurodegenerative diseases. In this context, the relationship between dementia and wine use/abuse has received increased research interest, with varying and often conflicting results. Scope and Approach: With this review, we aimed to critically summarize the main relevant studies to clarify the relationship between wine drinking and AD, as well as how frequency and/or amount of drinking may influence the effects. Key Findings and Conclusions: Overall, based on the interpretation of various studies, no definitive results highlight if light to moderate alcohol drinking is detrimental to cognition and dementia, or if alcohol intake could reduce risk of developing AD.


2020 ◽  
Vol 78 (3) ◽  
pp. 1119-1127
Author(s):  
Kathy Y. Liu ◽  
Harry Costello ◽  
Suzanne Reeves ◽  
Robert Howard ◽  

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.


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