scholarly journals Plasma neurofilament light as a longitudinal biomarker of neurodegeneration in Alzheimer’s disease

2019 ◽  
Vol 5 (2) ◽  
pp. 94-105 ◽  
Author(s):  
Ya-Nan Ou ◽  
Hao Hu ◽  
Zuo-Teng Wang ◽  
Wei Xu ◽  
Lan Tan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Rate Of Change ◽  
Neurofilament Light ◽  
Cox Proportional Hazards Models ◽  
Increased Risk ◽  
Β Amyloid ◽  
Longitudinal Biomarker

Objective: To examine whether plasma neurofilament light (NFL) might be a potential longitudinal biomarker for Alzheimer’s disease (AD). Methods: A total of 835 individuals from the Alzheimer’s Disease Neuroimaging Initiative were involved. Correlations of the rate of change in plasma NFL with cerebrospinal fluid biomarkers, cognition, and brain structure were investigated. Cox proportional hazards models were used to assess the associations between quartiles of plasma NFL and the risk of AD conversion. Results: Participants were further divided into β amyloid-positive (Aβ+) versus β amyloid-negative (Aβ−), resulting in five biomarker group combinations, which are CN Aβ−, CN Aβ+, MCI Aβ−, MCI Aβ+ and AD Aβ+. Plasma NFL concentration markedly increased in the five groups longitudinally ( p < 0.001) with the greatest rate of change in AD Aβ+ group. The rate of change in plasma NFL was associated with cognitive deficits and neuroimaging hallmarks of AD over time ( p < 0.005). Compared with the bottom quartile, the top quartile of change rate was associated with a 5.41-fold increased risk of AD (95% CI = 1.83−16.01) in the multivariate model. Conclusion: Our finding implies the potential of plasma NFL as a longitudinal noninvasive biomarker in AD.

scholarly journals Treatment of Sleep Disturbance May Reduce the Risk of Future Probable Alzheimer’s Disease

2018 ◽  
Vol 31 (2) ◽  
pp. 322-342 ◽  
Author(s):  
Shanna L. Burke ◽  
Tianyan Hu ◽  
Christine E. Spadola ◽  
Aaron Burgess ◽  
Tan Li ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Sleep Disturbance ◽  
Proportional Hazards ◽  
Secondary Analysis ◽  
Cox Proportional Hazards ◽  
Data Set ◽  
Proportional Hazards Regression ◽  
Increased Risk ◽  
Research Questions

Objective: This study explored two research questions: (a) Does sleep medication neutralize or provide a protective effect against the hazard of Alzheimer’s disease (AD)? (b) Do apolipoprotein (APOE) e4 carriers reporting a sleep disturbance experience an increased risk of AD? Method: This study is a secondary analysis of the National Alzheimer’s Coordinating Center’s Uniform Data Set ( n = 6,782) using Cox proportional hazards regression. Results: Sleep disturbance was significantly associated with eventual AD development. Among the subset of participants taking general sleep medications, no relationship between sleep disturbance and eventual AD was observed. Among individuals not taking sleep medications, the increased hazard between the two variables remained. Among APOE e4 carriers, sleep disturbance and AD were significant, except among those taking zolpidem. Discussion: Our findings support the emerging link between sleep disturbance and AD. Our findings also suggest a continued need to elucidate the mechanisms that offer protective factors against AD development.

Suicide risk within one year of cognitive impairment diagnosis in older adults: a nationwide retrospective cohort study

2019 ◽  
Author(s):  
Jae Woo Choi ◽  
Kang Soo Lee ◽  
Euna Han
Keyword(s):  
Alzheimer’S Disease ◽  
Older Adults ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mental Disorders ◽  
Suicide Risk ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Models ◽  
One Year

Abstract Background This study aims to investigate suicide risk within one year of receiving a diagnosis of cognitive impairment in older adults without mental disorders. Methods This study used National Health Insurance Service-Senior Cohort data on older adults with newly diagnosed cognitive impairment including Alzheimer’s disease, vascular dementia, other/unspecified dementia, and mild cognitive impairment from 2004 to 2012. We selected 41,195 older adults without cognitive impairment through 1:1 propensity score matching using age, gender, Charlson Comorbidity Index, and index year, with follow-up throughout 2013. We eliminated subjects with mental disorders and estimated adjusted hazard ratios (AHR) of suicide deaths within one year after diagnosis using the Cox proportional hazards models. Results We identified 49 suicide deaths during the first year after cognitive impairment diagnosis. The proportion of observed suicide deaths was the highest within one year after cognitive impairment diagnosis (48.5% of total); older adults with cognitive impairment were at a higher suicide risk than those without cognitive impairment (AHR, 1.89; 95% confidence interval [CI], 1.18–3.04). Subjects with Alzheimer’s disease and other/unspecified dementia were at greater suicide risk than those without cognitive impairment (AHR, 1.94, 1.94; 95% CI, 1.12–3.38, 1.05–3.58). Suicide risk in female and young-old adults (60–74 years) with cognitive impairment was higher than in the comparison group (AHR, 2.61, 5.13; 95% CI, 1.29–5.28, 1.48–17.82). Conclusions Older patients with cognitive impairment were at increased suicide risk within one year of diagnosis. Early intervention for suicide prevention should be provided to older adults with cognitive impairment.

scholarly journals Mid- and Late-Life Migraine Is Associated with an Increased Risk of All-Cause Dementia and Alzheimer’s Disease, but Not Vascular Dementia: A Nationwide Retrospective Cohort Study

2021 ◽  
Vol 11 (10) ◽  
pp. 990
Author(s):  
Hyun-Joo Lee ◽  
Hyunjae Yu ◽  
Son Gil Myeong ◽  
Kijoon Park ◽  
Dong-Kyu Kim
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Vascular Dementia ◽  
Proportional Hazards ◽  
Comparison Group ◽  
Late Life ◽  
Cox Proportional Hazards ◽  
Increased Risk ◽  
Migraine Group ◽  
Prospective Association

We used a nationwide cohort sample of data from 2002 to 2013, representing approximately 1 million patients to investigate the prospective association between migraine and dementia. The migraine group (n = 1472) included patients diagnosed between 2002 and 2004, aged over 55 years; the comparison group was selected using propensity score matching (n = 5888). Cox proportional hazards regression analyses was used to calculate the hazard ratios (HRs). The incidence of dementia was 13.5 per 1000 person-years in the migraine group. Following adjustment for sociodemographic and comorbidities variables, patients with migraine developed dementia more frequently than those in the comparison group (adjusted HR = 1.37, 95% confidence interval [CI], 1.16–1.61). In the subgroup analysis, we found a higher HR of dementia events in male, the presence of comorbidities, and older age (≥65) patients with migraine, compared to those without migraine. Moreover, patients with migraine had a significantly higher incidence of Alzheimer’s disease (adjusted HR = 1.31, 95% CI, 1.08–1.58), but not vascular dementia, than those without migraine. Therefore, our findings suggest that mid- and late-life migraines may be associated with an increased incidence of all-cause dementia and Alzheimer’s disease, but not vascular dementia.

Confrontation naming does not add incremental diagnostic utility in MCI and Alzheimer's disease

2004 ◽  
Vol 10 (4) ◽  
pp. 504-512 ◽  
Author(s):  
JULIE A. TESTA ◽  
ROBERT J. IVNIK ◽  
BRADLEY BOEVE ◽  
RONALD C. PETERSEN ◽  
V. SHANE PANKRATZ ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Regression Analysis ◽  
Proportional Hazards ◽  
Normal Subjects ◽  
Cox Proportional Hazards ◽  
Diagnostic Utility ◽  
Delayed Recall ◽  
Increased Risk ◽  
Cognitively Normal Subjects

As the incidence of dementia increases, there is a growing need to determine the diagnostic utility of specific neuropsychological tests in the early diagnosis of Alzheimer's disease (AD). In this study, the relative utility of Boston Naming Test (BNT) in the diagnosis of AD was examined and compared to the diagnostic utility of other neuropsychological measures commonly used in the evaluation of AD. Individuals with AD (n = 306), Mild Cognitive Impairment (MCI; n = 67), and cognitively normal subjects (n = 409) with at least 2 annual evaluations were included. Logistic regression analysis suggested that initial BNT impairment is associated with increased risk of subsequent AD diagnosis. However, this risk is significantly less than that imparted by measures of delayed recall impairments. A multivariate Cox proportional hazards regression analysis suggested that BNT impairment imparted no additional risk for subsequent AD diagnosis after delayed recall impairments were included in the model. Although BNT impairment occurred in all severity groups, it was ubiquitous only in moderate to severe dementia. Collectively these results suggest that although BNT impairments become more common as AD progresses, they are neither necessary for the diagnosis of AD nor particularly useful in identifying early AD. (JINS, 2004, 10, 504–512.)

scholarly journals Plasma Brain-Derived Neurotropic Factor Levels Are Associated with Aging and Smoking But Not with Future Dementia in the Rotterdam Study

2021 ◽  
Vol 80 (3) ◽  
pp. 1139-1149
Author(s):  
Sara Galle ◽  
Silvan Licher ◽  
Maarten Milders ◽  
Jan Berend Deijen ◽  
Erik Scherder ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Proportional Hazards ◽  
Long Term Potentiation ◽  
Cox Proportional Hazards ◽  
Activity Level ◽  
Rotterdam Study ◽  
Increased Risk ◽  
Neurotropic Factor

Background: Brain-derived neurotropic factor (BDNF) plays a vital role in neuronal survival and plasticity and facilitates long-term potentiation, essential for memory. Alterations in BDNF signaling have been associated with cognitive impairment, dementia, and Alzheimer’s disease. Although peripheral BDNF levels are reduced in dementia patients, it is unclear whether changes in BDNF levels precede or follow dementia onset. Objective: In the present study, we examined the association between BDNF plasma levels and dementia risk over a follow-up period of up to 16 years. Methods: Plasma BDNF levels were assessed in 758 participants of the Rotterdam Study. Dementia was assessed from baseline (1997–1999) to follow-up until January 2016. Associations of plasma BDNF and incident dementia were assessed with Cox proportional hazards models, adjusted for age and sex. Associations between plasma BDNF and lifestyle and metabolic factors are investigated using linear regression. Results: During a follow up of 3,286 person-years, 131 participants developed dementia, of whom 104 had Alzheimer’s disease. We did not find an association between plasma BDNF and risk of dementia (adjusted hazard ratio 0.99; 95%CI 0.84–1.16). BDNF levels were positively associated with age (B = 0.003, SD = 0.001, p = 0.002), smoking (B = 0.08, SE = 0.01, p = < 0.001), and female sex (B = 0.03, SE = 0.01, p = 0.03), but not with physical activity level (B = –0.01, SE = 0.01, p = 0.06). Conclusion: The findings suggest that peripheral BDNF levels are not associated with an increased risk of dementia.

scholarly journals No increased risk of Alzheimer’s disease among people with immune-mediated inflammatory diseases: findings from a longitudinal cohort study of U.S. older adults

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Michael J. Booth ◽  
Lindsay C. Kobayashi ◽  
Mary R. Janevic ◽  
Daniel Clauw ◽  
John D. Piette
Keyword(s):  
Alzheimer’S Disease ◽  
Older Adults ◽  
Alzheimer's Disease ◽  
Proportional Hazards ◽  
Inflammatory Diseases ◽  
Large Population ◽  
Cox Proportional Hazards ◽  
Medicare Claims ◽  
Immune Mediated ◽  
Increased Risk

Abstract Objective Immune-mediated inflammatory diseases (IMID) are characterized by systemic inflammation affecting the joints and bodily organs. Studies examining the association between individual IMIDs and the risk of Alzheimer’s disease (AD) have yielded inconsistent findings. This study examines AD risk across a group of IMIDs in a large population-based sample of older adults. Methods Data on a national sample of US adults over age 50 was drawn from the Health and Retirement Study (HRS) and linked Medicare claims from 2006 to 2014. IMIDs include rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, ulcerative colitis, and related conditions. We identified IMIDs from 2006 to 2009 Medicare claims using International Classification of Diseases (ICD9-CM) codes. The date of incident AD was derived from Chronic Conditions Warehouse (CCW) identifiers. We examined the risk of AD from 2009 to 2014 using Cox proportional hazards models, both unadjusted and adjusted for age, gender, education, race, and the genetic risk factor APOE-e4. Results One hundred seventy-one (6.02%) of the 2842 total HRS respondents with Medicare coverage and genetic data were classified with IMIDs. Over the subsequent 6 years, 9.36% of IMID patients developed AD compared to 8.57% of controls (unadjusted hazard ratio (HR): 1.09, 95% CI .66–1.81, p = 0.74). Adjusted HR 1.27 (95% CI 0.76–2.12, p = 0.35). Age (HR for 10-year increment 3.56, p < .001), less than high school education (HR 1.70, p = .007), and APOE-e4 (HR 2.61, p < .001 for one or two copies), were also statistically significant predictors of AD. Conclusion HRS respondents with common IMIDs do not have increased risk of Alzheimer’s disease over a 6-year period.

scholarly journals Activity Fractionation Moderates the Relationship of Gait Speed With Alzheimer’s Disease Risk

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 161-162
Author(s):  
Yang An ◽  
Jennifer Schrack ◽  
Pei-Lun Kuo ◽  
Amal Wanigatunga ◽  
Eleanor Simonsick ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Gait Speed ◽  
Proportional Hazards ◽  
Disease Risk ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Models ◽  
Relationship Of ◽  
The Relationship

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.

Abstract P103: Association Of Lipid Variability With Incident Alzheimers Disease And Alzheimers Disease Related Dementias

Circulation ◽  
2021 ◽  
Vol 143 (Suppl_1) ◽  
Author(s):  
Ethan D Moser ◽  
Sheila M Manemann ◽  
Nicholas B Larson ◽  
Jennifer L St Sauver ◽  
Paul Y Takahashi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Risk Factor ◽  
Total Cholesterol ◽  
Proportional Hazards ◽  
Final Analysis ◽  
Cox Proportional Hazards ◽  
Alzheimers Disease ◽  
Increased Risk ◽  
Common Clinical Practice

Background: Prevention strategies for Alzheimer’s disease and Alzheimer’s disease related dementias (AD/ADRDs) are urgently needed for reducing incidence. Intra-patient variability in lipid levels is a potentially modifiable risk factor for incident AD/ADRD. Although regular lipid measurements are a part of common clinical practice and longitudinal data routinely available in electronic health records (EHR), research examining this association between AD/ADRD and lipid variability across multiple lipid types remains scarce. Methods: All residents living in Olmsted County, MN on 1/1/2006 age ≥60 years without an AD/ADRD diagnosis were identified using Centers for Medicare & Medicaid Services diagnostic codes. Persons with ≥3 lipid measurements (total cholesterol or triglycerides) in the 5 years prior to index date were retained. Lipid variability was quantified using variability independent of the mean (VIM). Models were adjusted for traditional risk factors. Associations between lipid variability quintiles and incident AD/ADRD were assessed using Cox proportional hazards regression. Multiple imputation was used for missing covariates. Participants were followed through 2018 for incident AD/ADRD. Results: The final analysis included data on 11,551 participants with total cholesterol and 11,502 participants with triglycerides. Participants had a mean age of 71 (range 60-99) years, and were primarily white (96%). Females (54%) were also slightly more frequent than males. Median follow up was 12.9 years (range: 0-13). Participants in the highest quintile of variability for total cholesterol and triglycerides had a 20% increased risk of incident AD/ADRD. Similar results were found in the subset with complete covariate data. Conclusion: In a large EHR derived cohort, persons in the highest quintile of lipid variation had an increased risk of incident AD/ADRD. Further studies to identify the mechanisms behind this risk factor and replication of these results across a more diverse population are needed.

scholarly journals Continuous and Cyclic Progesterone Differentially Interact with Estradiol in the Regulation of Alzheimer-Like Pathology in Female 3×Transgenic-Alzheimer’s Disease Mice

Endocrinology ◽  
2010 ◽  
Vol 151 (6) ◽  
pp. 2713-2722 ◽  
Author(s):  
Jenna C. Carroll ◽  
Emily R. Rosario ◽  
Angela Villamagna ◽  
Christian J. Pike
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Postmenopausal Women ◽  
Transgenic Mouse Model ◽  
Dependent Behavior ◽  
Potential Efficacy ◽  
Increased Risk ◽  
Neural Interactions ◽  
Β Amyloid ◽  
Insight Into

Depletion of estrogens and progesterone at menopause has been linked to an increased risk for the development of Alzheimer’s disease (AD) in women. A currently controversial literature indicates that although treatment of postmenopausal women with hormone therapy (HT) may reduce the risk of AD, several parameters of HT may limit its potential efficacy and perhaps, even exacerbate AD risk. One such parameter is continuous vs. cyclic delivery of the progestogen component of HT. Recent experimental evidence suggests that continuous progesterone can attenuate neural actions of estradiol (E2). In the present study, we compared the effects of continuous and cyclic progesterone treatment in the presence and absence of E2 in ovariectomized 3×Tg-AD mice, a transgenic mouse model of AD. We found that ovariectomy-induced hormone depletion increases AD-like pathology in female 3×Tg-AD mice, including accumulation of β-amyloid, tau hyperphosphorylation, and impaired hippocampal-dependent behavior. E2 treatment alone prevents the increases in pathology. Continuous progesterone did not affect β-amyloid levels when delivered alone but blocked the Aβ-lowering action of E2. In contrast, cyclic progesterone significantly reduced β-amyloid levels by itself and enhanced rather than inhibited the E2 effects. These results provide new insight into the neural interactions between E2 and progesterone that may prove valuable in optimizing HT regimens in postmenopausal women.

scholarly journals Changes in Metabolic Syndrome Status and Breast Cancer Risk: A Nationwide Cohort Study

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1177
Author(s):  
In Young Choi ◽  
Sohyun Chun ◽  
Dong Wook Shin ◽  
Kyungdo Han ◽  
Keun Hye Jeon ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metabolic Syndrome ◽  
Proportional Hazards ◽  
Screening Program ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Models ◽  
Hazard Ratios ◽  
Increased Risk ◽  
Health Screening Program ◽  
Design And Methods

Objective: To our knowledge, no studies have yet looked at how the risk of developing breast cancer (BC) varies with changes in metabolic syndrome (MetS) status. This study aimed to investigate the association between changes in MetS and subsequent BC occurrence. Research Design and Methods: We enrolled 930,055 postmenopausal women aged 40–74 years who participated in a biennial National Health Screening Program in 2009–2010 and 2011–2012. Participants were categorized into four groups according to change in MetS status during the two-year interval screening: sustained non-MetS, transition to MetS, transition to non-MetS, and sustained MetS. We calculated multivariable-adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for BC incidence using the Cox proportional hazards models. Results: At baseline, MetS was associated with a significantly increased risk of BC (aHR 1.11, 95% CI 1.06–1.17) and so were all of its components. The risk of BC increased as the number of the components increased (aHR 1.46, 95% CI 1.26–1.61 for women with all five components). Compared to the sustained non-MetS group, the aHR (95% CI) for BC was 1.11 (1.04–1.19) in the transition to MetS group, 1.05 (0.96–1.14) in the transition to non-MetS group, and 1.18 (1.12–1.25) in the sustained MetS group. Conclusions: Significantly increased BC risk was observed in the sustained MetS and transition to MetS groups. These findings are clinically meaningful in that efforts to recover from MetS may lead to reduced risk of BC.

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