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

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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Potentially Modifiable Risk Factors in the Development of Alzheimer’s Disease

US Neurology ◽

10.17925/usn.2010.05.02.18 ◽

2010 ◽

Vol 05 (02) ◽

pp. 18 ◽

Cited By ~ 2

Author(s):

Simon Forstmeier ◽

Andreas Maercker ◽

◽

Keyword(s):

Risk Factors ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Emotional Health ◽

Social Activity ◽

Empirical Support ◽

Epidemiological Studies ◽

Vascular Risk Factors ◽

Modifiable Risk Factors ◽

Vascular Risk

This article summarises empirical findings on major potentially modifiable risk factors in the development of Alzheimer’s disease (AD), drawing on data from longitudinal epidemiological studies on the incidence of AD or any-cause dementia. Risk factors investigated to date include cognitive ability, motivational ability, emotional health, physical activity, social activity and social network, vascular risk factors and nutrition. The authors find most empirical support for two main clusters of risk factors that also represent potential targets for prevention. First, an active and stimulating lifestyle including cognitive, social, and physical activities reduces the risk of AD. Second, the absence of vascular risk factors such as diabetes, hypertension, hypercholesterol and obesity reduces the risk of AD. More prevention trials are warranted to investigate the preventative effects of an active and stimulating lifestyle on the one hand, and vascular health on the other, in delaying the onset of AD or slowing its progression.

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Progression of Alzheimer’s disease, tau propagation, and its modifiable risk factors

Neuroscience Research ◽

10.1016/j.neures.2018.08.005 ◽

2019 ◽

Vol 141 ◽

pp. 36-42 ◽

Cited By ~ 14

Author(s):

Shuko Takeda

Keyword(s):

Risk Factors ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Modifiable Risk Factors

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

Stroke ◽

10.1161/str.46.suppl_1.tp160 ◽

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.

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P3-039: The relationship between blood pressure and incident Alzheimer's disease: A systematic review and meta-analysis

Alzheimer s & Dementia ◽

10.1016/j.jalz.2010.05.1532 ◽

2010 ◽

Vol 6 ◽

pp. S460-S460

Author(s):

Melinda C. Power ◽

Jennifer Weuve ◽

Joshua Gagne ◽

Matthew B. McQueen ◽

Deborah Blacker

Keyword(s):

Systematic Review ◽

Alzheimer’S Disease ◽

Blood Pressure ◽

Alzheimer's Disease ◽

Meta Analysis ◽

The Relationship

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Prediction of Alzheimer’s disease biomarker status defined by the ‘ATN framework’ among cognitively healthy individuals: results from the EPAD longitudinal cohort study

Alzheimer s Research & Therapy ◽

10.1186/s13195-020-00711-5 ◽

2020 ◽

Vol 12 (1) ◽

Author(s):

Catherine M. Calvin ◽

◽

Casper de Boer ◽

Vanessa Raymont ◽

John Gallacher ◽

...

Keyword(s):

Risk Factors ◽

Alzheimer’S Disease ◽

Blood Pressure ◽

Alzheimer's Disease ◽

Family History ◽

Risk Scores ◽

Healthy Individuals ◽

Disease Biomarker ◽

Composite Risk ◽

Composite Scores

Abstract Background The Amyloid/Tau/Neurodegeneration (ATN) framework has been proposed as a means of evidencing the biological state of Alzheimer’s disease (AD). Predicting ATN status in pre-dementia individuals therefore provides an important opportunity for targeted recruitment into AD interventional studies. We investigated the extent to which ATN-defined biomarker status can be predicted by known AD risk factors as well as vascular-related composite risk scores. Methods One thousand ten cognitively healthy older adults were allocated to one of five ATN-defined biomarker categories. Multinomial logistic regression tested risk factors including age, sex, education, APOE4, family history of dementia, cognitive function, vascular risk indices (high systolic blood pressure, body mass index (BMI), high cholesterol, physical inactivity, ever smoked, blood pressure medication, diabetes, prior cardiovascular disease, atrial fibrillation and white matter lesion (WML) volume), and three vascular-related composite scores, to predict five ATN subgroups; ROC curve models estimated their added value in predicting pathology. Results Age, APOE4, family history, BMI, MMSE and white matter lesions (WML) volume differed between ATN biomarker groups. Prediction of Alzheimer’s disease pathology (versus normal AD biomarkers) improved by 7% after adding family history, BMI, MMSE and WML to a ROC curve that included age, sex and APOE4. Risk composite scores did not add value. Conclusions ATN-defined Alzheimer’s disease biomarker status prediction among cognitively healthy individuals is possible through a combination of constitutional and cardiovascular risk factors but established dementia composite risk scores do not appear to add value in this context.

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

Journal of Alzheimer s Disease ◽

10.3233/jad-200516 ◽

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.

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Role of nurses in addressing modifiable risk factors for early Alzheimer's disease and mild cognitive impairment

British Journal of Nursing ◽

10.12968/bjon.2020.29.8.460 ◽

2020 ◽

Vol 29 (8) ◽

pp. 460-469 ◽

Cited By ~ 1

Author(s):

Kevin Hope

Keyword(s):

Risk Factors ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Cognitive Decline ◽

Health Professionals ◽

Current Evidence ◽

Modifiable Risk Factors ◽

Early Alzheimer’S Disease

A multidisciplinary advisory group of health professionals involved in dementia care assessed the current evidence base regarding modifiable risk factors (MRFs) for early Alzheimer's disease and mild cognitive impairment. Based on evidence from the published literature and clinical experience, MRFs in four areas were identified where there is evidence to support interventions that may help delay cognitive decline or reduce the risk of developing Alzheimer's disease: medical (eg cardiovascular risk factors), psychosocial (eg depression, anxiety, social isolation), lifestyle (eg lack of physical activity, smoking) and nutrition (eg poor diet, lack of micronutrients). Practical guidance on how health professionals, but in particular nurses, may actively seek to address these MRFs in clinical practice was also developed. Nurses are at the forefront of patient care and, as such, are ideally placed to offer advice to patients that may proactively help mitigate the risks of cognitive decline and the development of Alzheimer's disease.

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