Impaired Insulin Sensitivity and Secretion in Patients with Alzheimer's Disease: The Relationship with Other Atherosclerosis Risk Factors

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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The relationship between Alzheimer's disease and vascular risk factors

The FASEB Journal ◽

10.1096/fasebj.2020.34.s1.02068 ◽

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

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

10.1101/229062 ◽

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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Relationship between Sum of the Four Limbs’ Pulse Pressure and Brachial-Ankle Pulse Wave Velocity and Atherosclerosis Risk Factors in Chinese Adults

BioMed Research International ◽

10.1155/2015/434516 ◽

2015 ◽

Vol 2015 ◽

pp. 1-7 ◽

Cited By ~ 1

Author(s):

Yansong Zheng ◽

Zongbin Li ◽

Hua Shu ◽

Minyan Liu ◽

Zhilai Chen ◽

...

Keyword(s):

Risk Factors ◽

Pulse Wave Velocity ◽

Wave Velocity ◽

Pulse Pressure ◽

Pulse Wave ◽

Health Examination ◽

Atherosclerosis Risk ◽

Different Populations ◽

Atherosclerosis Risk Factors ◽

The Relationship

The aim of the present study was to analyze the relationship between the sum of the four limbs’ pulse pressure (Sum-PP) and brachial-ankle pulse wave velocity (baPWV) and atherosclerosis risk factors and evaluate the feasibility of Sum-PP in diagnosing atherosclerosis systemically. For the purpose, a cross-sectional study was conducted on the basis of medical information of 20748 adults who had a health examination in our hospital. Both Sum-PP and baPWV exhibited significant variations among different human populations grouped by gender, smoking, drinking, and age. Interestingly, Sum-PP had similar varying tendency with baPWV in different populations. And further study in different populations showed that Sum-PP was significantly positively related to baPWV. We also investigated the relationship between Sum-PP, baPWV, and cardiovascular risk factors, respectively. We found that both Sum-PP and baPWV had significant positive correlation with atherosclerosis risk factors while both of them were negatively related to HDL-c. In addition, there was a significant close correlation between Sum-PP and baPWV in the whole population (r=0.4616,P<0.0001). Thus, Sum-PP is closely related to baPWV and is of important value for clinical diagnosis of atherosclerosis.

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Investigating the relationship between DNA methylation age acceleration and risk factors for Alzheimer's disease

Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring ◽

10.1016/j.dadm.2018.05.006 ◽

2018 ◽

Vol 10 (1) ◽

pp. 429-437 ◽

Cited By ~ 21

Author(s):

Daniel L. McCartney ◽

Anna J. Stevenson ◽

Rosie M. Walker ◽

Jude Gibson ◽

Stewart W. Morris ◽

...

Keyword(s):

Risk Factors ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Dna Methylation ◽

Dna Methylation Age ◽

The Relationship

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Examining the Relationship between Trace Lithium in Drinking Water and the Rising Rates of Age-Adjusted Alzheimer’s Disease Mortality in Texas

Journal of Alzheimer s Disease ◽

10.3233/jad-170744 ◽

2017 ◽

Vol 61 (1) ◽

pp. 425-434 ◽

Cited By ~ 19

Author(s):

Val Andrew Fajardo ◽

Val Andrei Fajardo ◽

Paul J. LeBlanc ◽

Rebecca E.K. MacPherson

Keyword(s):

Risk Factors ◽

Alzheimer’S Disease ◽

Type 2 Diabetes ◽

Alzheimer's Disease ◽

Drinking Water ◽

Physical Inactivity ◽

Mortality Rates ◽

The Relationship ◽

Over Time

Background: Alzheimer’s disease (AD) mortality rates have steadily increased over time. Lithium, the current gold standard treatment for bipolar disorder, can exert neuroprotective effects against AD. Objective: We examined the relationship between trace levels of lithium in drinking water and changes in AD mortality across several Texas counties. Methods: 6,180 water samples from public wells since 2007 were obtained and averaged for 234 of 254 Texas counties. Changes in AD mortality rates were calculated by subtracting aggregated age-adjusted mortality rates obtained between 2000–2006 from those obtained between 2009–2015. Using aggregated rates maximized the number of counties with reliable mortality data. Correlational analyses between average lithium concentrations and changes in AD mortality were performed while also adjusting for gender, race, education, rural living, air pollution, physical inactivity, obesity, and type 2 diabetes. Results: Age-adjusted AD mortality rate was significantly increased over time (+27%, p < 0.001). Changes in AD mortality were negatively correlated with trace lithium levels (p = 0.01, r = –0.20), and statistical significance was maintained after controlling for most risk factors except for physical inactivity, obesity, and type 2 diabetes. Furthermore, the prevalence of obesity and type 2 diabetes positively correlated with changes in AD mortality (p = 0.01 and 0.03, respectively), but also negatively correlated with trace lithium in drinking water (p = 0.05 and <0.0001, respectively). Conclusion: Trace lithium in water is negatively linked with changes in AD mortality, as well as obesity and type 2 diabetes, which are important risk factors for AD.

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DNA methylation age acceleration and risk factors for Alzheimer’s disease

10.1101/278945 ◽

2018 ◽

Author(s):

Daniel L McCartney ◽

Anna J Stevenson ◽

Rosie M Walker ◽

Jude Gibson ◽

Stewart W Morris ◽

...

Keyword(s):

Risk Factors ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Dna Methylation ◽

Environmental Risk ◽

Environmental Risk Factors ◽

Biological Age ◽

Chronological Age ◽

Epigenetic Clock ◽

The Relationship

AbstractINTRODUCTIONThe ‘epigenetic clock’ is a DNA methylation-based estimate of biological age and is correlated with chronological age – the greatest risk factor for Alzheimer’s disease (AD). Genetic and environmental risk factors exist for AD, several of which are potentially modifiable. Here, we assess the relationship associations between the epigenetic clock and AD risk factors.METHODSLinear mixed modelling was used to assess the relationship between age acceleration (the residual of biological age regressed onto chronological age) and AD risk factors relating to cognitive reserve, lifestyle, disease, and genetics in the Generation Scotland study (n=5,100).RESULTSWe report significant associations between the epigenetic clock and BMI, total:HDL cholesterol ratios, socioeconomic status, and smoking behaviour (Bonferroni-adjusted P<0.05).DISCUSSIONAssociations are present between environmental risk factors for AD and age acceleration. Measures to modify such risk factors might improve the risk profile for AD and the rate of biological ageing. Future longitudinal analyses are therefore warranted.

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Recent Breakthroughs in Alzheimer's Disease: Risk Factors, Biological Markers, Cognitive and Linguistic Distinctions, and Pharmacological Interventions

Perspectives on Neurophysiology and Neurogenic Speech and Language Disorders ◽

10.1044/nnsld7.4.4 ◽

1997 ◽

Vol 7 (4) ◽

pp. 4-5

Author(s):

Sandra Bond Chapman

Keyword(s):

Risk Factors ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Biological Markers ◽

Disease Risk ◽

Pharmacological Interventions

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

Current Alzheimer Research ◽

10.2174/1567205017666201130094259 ◽

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.

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