scholarly journals DIABETES MITIGATES THE ROLE OF MEMORY COMPLAINT IN PREDICTING DEMENTIA RISK: RESULTS FROM THE PREVENTION OF ALZHEIMER’S DISEASE WITH VITAMIN E AND SELENIUM STUDY

2017 ◽  
pp. 1-6
Author(s):  
X. Zhang ◽  
F.A. Schmitt ◽  
A.M. Caban-Holt ◽  
X. Ding ◽  
R.J. Kryscio ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Vitamin E ◽  
Cancer Prevention ◽  
Black Men ◽  
Bypass Graft ◽  
Prevention Trial ◽  
Dementia Risk ◽  
Increased Risk

Background: Subjective memory complaints (SMCs) are associated with increased risk of dementia in older adults, but the role of comorbidities in modifying this risk is unknown. Objectives: To assess whether comorbidities modify estimated dementia risk based on SMCs. Design: The Prevention of Alzheimer’s Disease with Vitamin E and Selenium Study (PREADVISE) was designed as an ancillary study to the Selenium and Vitamin E Cancer Prevention Trial (SELECT), a randomized, multi-center prostate cancer prevention trial with sites in the Unites States, Puerto Rico, and Canada. In 2009, PREADVISE and SELECT were changed into cohort studies. Setting: Secondary analysis of PREADVISE data. Participants: PREADVISE recruited 7,540 non-demented male volunteers from participating SELECT sites from 2002 to 2009. SMCs, demographics, and comorbidities including hypertension, diabetes, coronary artery bypass graft (CABG), stroke, sleep apnea, and head injury were ascertained by participant interview. Measurements: Cox models were used to investigate whether baseline comorbidities modified hazard ratios (HR) for SMC-associated dementia risk using two methods: (1) we included one interaction term between SMC and a comorbidity in the model at a time, and (2) we included all two-way interactions between SMC and covariates of interest and reduced the model by “backward” selection. SMC was operationalized as any complaint vs. no complaint. Results: Baseline SMCs were common (23.6%). In the first analyses, with the exception of stroke, presence of self-reported comorbidities was associated with lower estimated HR for dementia based on SMC status (complaint vs. no complaint), but this difference was only significant for diabetes. In the second analysis, the two-way interactions between SMC and race as well as SMC and diabetes were significant. Here, black men without diabetes who reported SMC had the highest estimated dementia risk (HR=5.05, 95% CI 2.55-10.00), while non-black men with diabetes who reported SMC had the lowest estimated risk (HR=0.71, 95% CI 0.35-1.41). Conclusions: SMCs were more common among men with comorbidities, but these complaints appeared to be less predictive of dementia risk than those originating from men without comorbidities, suggesting that medical conditions such as diabetes may explain SMCs that are unrelated to an underlying neurodegenerative process.

scholarly journals Self-Reported Sleep Apnea and Dementia Risk: Findings from the Prevention of Alzheimer's Disease with Vitamin E and Selenium Trial

2016 ◽  
Vol 64 (12) ◽  
pp. 2472-2478 ◽  
Author(s):  
Xiuhua Ding ◽  
Richard J. Kryscio ◽  
Joshua Turner ◽  
Gregory A. Jicha ◽  
Gregory Cooper ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Vitamin E ◽  
Sleep Apnea ◽  
Dementia Risk

scholarly journals Polymorphisms inHSD17B1: Early Onset and Increased Risk of Alzheimer’s Disease in Women with Down Syndrome

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Joseph H. Lee ◽  
Susan Gurney ◽  
Deborah Pang ◽  
Alexis Temkin ◽  
Naeun Park ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Down Syndrome ◽  
Age At Onset ◽  
Nucleotide Polymorphisms ◽  
Risk Alleles ◽  
Increased Risk ◽  
Estrogen Activity ◽  
Intron 4

Background/Aims. Genetic variants that affect estrogen activity may influence the risk of Alzheimer's disease (AD). In women with Down syndrome, we examined the relation of polymorphisms in hydroxysteroid-17beta-dehydrogenase (HSD17B1) to age at onset and risk of AD.HSD17B1encodes the enzyme 17β-hydroxysteroid dehydrogenase (HSD1), which catalyzes the conversion of estrone to estradiol.Methods. Two hundred and thirty-eight women with DS, nondemented at baseline, 31–78 years of age, were followed at 14–18-month intervals for 4.5 years. Women were genotyped for 5 haplotype-tagging single-nucleotide polymorphisms (SNPs) in theHSD17B1gene region, and their association with incident AD was examined.Results. Age at onset was earlier, and risk of AD was elevated from two- to threefold among women homozygous for the minor allele at 3 SNPs in intron 4 (rs676387), exon 6 (rs605059), and exon 4 inCOASY(rs598126). Carriers of the haplotype TCC, based on the risk alleles for these three SNPs, had an almost twofold increased risk of developing AD (hazard ratio = 1.8, 95% CI, 1.1–3.1).Conclusion. These findings support experimental and clinical studies of the neuroprotective role of estrogen.

scholarly journals Genome research in pre-dementia stages of Alzheimer's disease

2016 ◽  
Vol 18 ◽  
Author(s):  
Sonia Moreno-Grau ◽  
Agustín Ruiz
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Late Onset ◽  
Subjective Cognitive Decline ◽  
Genetic Profile ◽  
Amyloid Deposits ◽  
Dementia Risk ◽  
Meta Analyses ◽  
Brain Insults

Genetic characterization of individuals at risk of Alzheimer's disease (AD), i.e. people having amyloid deposits in the brain without symptoms, people suffering from subjective cognitive decline (SCD) or mild cognitive impairment (MCI), has spurred the interests of researchers. However, their pre-dementia genetic profile remains mostly unexplored. In this study, we reviewed the loci related to phenotypes of AD, MCI and SCD from literature and performed the first meta-analyses evaluating the role of apolipoprotein E (APOE) in the risk of conversion from a healthy status to MCI and SCD. For AD dementia risk, an increased number of loci have been identified; to date, 28 genes have been associated with Late Onset AD. In MCI syndrome,APOEis confirmed as a pheno-conversion factor leading from MCI to AD, and clusterin is a promising candidate. Additionally, our meta-analyses revealedAPOEas genetic risk factor to convert from a healthy status to MCI [OR = 1.849 (1.587–2.153);P = 2.80  × 10−15] and to a lesser extent from healthy status to SCD [OR = 1.151 (1.015–1.304);P = 0.028]. Thus, we believe that genetic studies in longitudinal SCD and MCI series may provide new therapeutic targets and improve the existing knowledge of AD. This type of studies must be completed on healthy subjects to better understand the natural disease resistance to brain insults and neurodegeneration.

THREE CARDINAL LESSONS FROM ADAPT – 10 YEARS ON

2014 ◽  
pp. 1-5
Author(s):  
J.C.S. Breitner ◽  
C.G. Lyketsos
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Trial Design ◽  
Naproxen Sodium ◽  
Prevention Trial ◽  
Phase Iii ◽  
Increased Risk ◽  
Phase Iii Trials ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

The Alzheimer’s Disease Anti-inflammatory Prevention Trial was a placebo-controlled three-arm pharmaco-prevention trial of the non-steroidal anti-inflammatory drugs naproxen sodium and celecoxib for prevention of incident Alzheimer’s disease (AD) dementia in older (aged 70 and over) adults. Although subjects were at increased risk of symptoms because of a firstdegree family history, they were meant to be cognitively healthy at enrollment. ADAPT encountered several problems that resulted in the termination of its treatments after only two years on average. Interim results were complex but potentially interesting. In the end, however, the results were null. We describe the complications that prevented ADAPT from achieving conclusive results, and suggest that these could have been avoided if the trial design and execution had been better guided by preliminary data. We believe such data should be available before beginning further ambitious phase III trials of this sort, and we suggest a broad method by which such data can be accumulated with reasonable economy.

scholarly journals Affective Neuropsychiatric Symptoms as Early Signs of Dementia Risk in Older Adults

2020 ◽  
Vol 77 (3) ◽  
pp. 1195-1207
Author(s):  
Jung Yun Jang ◽  
Jean K. Ho ◽  
Anna E. Blanken ◽  
Shubir Dutt ◽  
Daniel A. Nation ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Older Adults ◽  
Alzheimer's Disease ◽  
Latent Class ◽  
Neuropsychiatric Symptoms ◽  
Community Dwelling ◽  
Dementia Risk ◽  
Increased Risk ◽  
Risk Of Progression

Background: Affective neuropsychiatric symptoms (aNPS: depression, anxiety, apathy, irritability) have been linked to increased dementia risk. However, less is known whether this association is independent of Alzheimer’s disease (AD) pathophysiology. Objective: To investigate the contribution of early aNPS to dementia risk in cognitively normal (CN) older adults and mild cognitive impairment (MCI) patients, with and without AD biomarker abnormality. Methods: Participants included 763 community-dwelling, stroke-free older adults identified as CN and 617 with MCI at baseline, drawn from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. Baseline assessments included a neuropsychological battery, the Neuropsychiatric Inventory (NPI), and apolipoprotein E ɛ4 (ApoE4) genotyping. A participant subset completed cerebrospinal fluid (CSF) AD biomarker assessment. Time to progression to dementia was measured based on months at follow-up when an individual was diagnosed with dementia, over the follow-up period of 48 months. Results: Latent class analysis identified 3 subgroups of older adults in CN and MCI, indicated by the baseline profiles of neuropsychiatric symptoms (NPS). Subgroups with higher aNPS were at increased risk of progression to dementia in both CN (HR = 3.65, 95% CI [1.80, 7.40]) and MCI (HR = 1.52, 95% CI [1.16, 2.00]; HR = 1.86 [1.05, 3.30]) groups, adjusting for age, sex, global cognition, and ApoE4, compared with their counterparts with minimal NPS. There was no difference between higher aNPS and minimal NPS subgroups in their CSF AD biomarker profiles. Conclusion: Findings suggest that aNPS may represent a neurobiological vulnerability that uniquely contribute to the dementia risk, independent of AD biomarker profiles.

Preference-weighted quality of life: Findings from the Selenium and Vitamin E Cancer Prevention Trial (SELECT).

2021 ◽  
Vol 39 (28_suppl) ◽  
pp. 144-144
Author(s):  
Matthew Rock ◽  
Riha Vaidya ◽  
Cathee Till ◽  
Joseph M. Unger ◽  
Dawn L. Hershman ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Vitamin E ◽  
Cancer Prevention ◽  
Black Men ◽  
Clinical Characteristics ◽  
Prevention Trial ◽  
Race Ethnicity ◽  
Hispanic White ◽  
Time Point

144 Background: The differences in preference-weighted health-related quality of life (HRQOL) among racial and ethnic groups have been previously reported. The Selenium and Vitamin E Cancer Prevention Trial (SELECT) enrolled 35,533 men aged 50 years and older, among whom 20% were minorities. HRQOL, using the SF-36V, was examined for a subset of participants. Using these survey data, we examined the preference-weighted HRQOL differences across the racial/ethnic categories included in SELECT. Methods: SELECT participants who completed the SF-36V at baseline, and subsequently in at least one of years 1, 3, and 5 were included. We used the SF-6D to calculate an HRQOL score ranging between 0 (worst possible) and 1 (best possible) for every participant using data from the SF-36V. We modeled the association of race/ethnicity with SF-6D scores using a linear mixed model adjusting for demographic and clinical characteristics. Results: At baseline, 9,691 men were eligible for analysis. Hispanic and non-Hispanic white participants had higher unadjusted mean SF-6D scores than non-Hispanic Black participants at baseline and every subsequent time point (p<0.05; Table). Non-Hispanic white participants had lower mean scores than Hispanic participants at every time point after baseline. After adjusting for demographic and clinical characteristics there are statistically significant differences in HRQOL among all three groups. In particular, Hispanic participants had higher scores than white participants by.074 (p<.001),.076 (p<.001), and.039 (p<.001) in years 1, 3, and 5 after baseline. Conversely, compared to non-Hispanic White participants, non-Hispanic Black participants had lower scores by.009 (p=.004) and.008 (p=.02) in years 1 and 3 after baseline. Conclusions: In this sample of men enrolled in a prostate cancer chemoprevention trial, preference-weighted HRQOL using the SF-6D was higher for Hispanic men than for white and Black men, and lower for Black men than for white men. Understanding how individuals belonging to different racial and/or ethnic categories view their own HRQOL is necessary not only for delivering culturally competent care but also for conducting accurate cost effectiveness analyses of new interventions and programs. Further research that includes a sample with women, reports on more categories of race/ethnicity, and explores underlying potential cultural and social differences is necessary. [Table: see text]

Sex Differences in Locus Coeruleus: A Heuristic Approach That May Explain the Increased Risk of Alzheimer’s Disease in Females

2021 ◽  
pp. 1-18
Author(s):  
Alison M. Luckey ◽  
Ian H. Robertson ◽  
Brian Lawlor ◽  
Anusha Mohan ◽  
Sven Vanneste
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Sex Differences ◽  
Locus Coeruleus ◽  
Neuroprotective Effects ◽  
Increased Risk ◽  
Brain Barrier Permeability ◽  
And Function ◽  
New Hypothesis

This article aims to reevaluate our approach to female vulnerability to Alzheimer’s disease (AD) and put forth a new hypothesis considering how sex differences in the locus coeruleus-noradrenaline (LC-NA) structure and function could account for why females are more likely to develop AD. We specifically focus our attention on locus coeruleus (LC) morphology, the paucity of estrogens, neuroinflammation, blood-brain barrier permeability, apolipoprotein ɛ4 polymorphism (APOE ɛ4), and cognitive reserve. The role of the LC-NA system and sex differences are two of the most rapidly emerging topics in AD research. Current literature either investigates the LC due to it being one of the first brain areas to develop AD pathology or acknowledges the neuroprotective effects of estrogens and how the loss of these female hormones have the capacity to contribute to the sex differences seen in AD; however, existing research has neglected to concurrently examine these two rationales and therefore leaving our hypothesis undetermined. Collectively, this article should assist in alleviating current challenges surrounding female AD by providing thought-provoking connections into the interrelationship between the disruption of the female LC-NA system, the decline of estrogens, and AD vulnerability. It is therefore likely that treatment for this heterogeneous disease may need to be distinctly developed for females and males separately, and may require a precision medicine approach.

scholarly journals The Role of HDL and HDL Mimetic Peptides as Potential Therapeutics for Alzheimer’s Disease

Biomolecules ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 1276
Author(s):  
Dustin Chernick ◽  
Rui Zhong ◽  
Ling Li
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Large Scale ◽  
Neurodegenerative Disorder ◽  
Current Evidence ◽  
High Density Lipoproteins ◽  
Increased Risk ◽  
Mimetic Peptides ◽  
The Brain

The role of high-density lipoproteins (HDL) in the cardiovascular system has been extensively studied and the cardioprotective effects of HDL are well established. As HDL particles are formed both in the systemic circulation and in the central nervous system, the role of HDL and its associated apolipoproteins in the brain has attracted much research interest in recent years. Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder and the leading cause of dementia worldwide, for which there currently exists no approved disease modifying treatment. Multiple lines of evidence, including a number of large-scale human clinical studies, have shown a robust connection between HDL levels and AD. Low levels of HDL are associated with increased risk and severity of AD, whereas high levels of HDL are correlated with superior cognitive function. Although the mechanisms underlying the protective effects of HDL in the brain are not fully understood, many of the functions of HDL, including reverse lipid/cholesterol transport, anti-inflammation/immune modulation, anti-oxidation, microvessel endothelial protection, and proteopathy modification, are thought to be critical for its beneficial effects. This review describes the current evidence for the role of HDL in AD and the potential of using small peptides mimicking HDL or its associated apolipoproteins (HDL-mimetic peptides) as therapeutics to treat AD.

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