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01/2020 journal articles

Editorials

GEROSCIENCE AND THE ROLE OF AGING IN THE ETIOLOGY AND MANAGEMENT OF ALZHEIMER’S DISEASE

F. Sierra

J Prev Alz Dis 2020;7(1):2-3

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CITATION:
F. Sierra (2019): Geroscience and the Role of Aging in the Etiology and Management of Alzheimer’s Disease. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2019.49

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SEARCHING FOR THE HOLY GRAIL WILL NEED BIOMARKERS

A. Ramirez

J Prev Alz Dis 2020;7(1):4-6

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CITATION:
A. Ramirez (2020): Searching for the Holy Grail Will Need Biomarkers. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2020.2

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Original Research

THE EUROPEAN PREVENTION OF ALZHEIMER’S DEMENTIA (EPAD) LONGITUDINAL COHORT STUDY: BASELINE DATA RELEASE V500.0

C.W. Ritchie, G. Muniz-Terrera, M. Kivipelto, A. Solomon, B. Tom, J.L. Molinuevo, On Behalf of the EPAD Consortium

J Prev Alz Dis 2020;7(1):8-13

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Background: The European Prevention of Alzheimer’s Dementia (EPAD) Programme is a pan-European project whose objective is to deliver a platform, adaptive, Phase 2 proof of concept (PoC) trial for the secondary prevention of Alzheimer’s dementia. A component of this platform is the Longitudinal Cohort Study (LCS) which acts as a readiness cohort for the PoC Trial as well as generating data for disease modelling work in the preclinical and prodromal phases of Alzheimer’s dementia. Objectives: The first data wave has been collected, quality checked, released and now available for analysis to answer numerous research questions. Here we describe the results from key variables in the EPAD LCS with the objective of using these results to compliment analyses of these data in the future. Design: EPAD LCS is a cohort study whose primary objective is as a readiness cohort for the EPAD PoC Trial. As such recruitment is not capped at any particular number but will continue to facilitate delivery of the EPAD PoC Trial. Research Participants are seen annually (with an additional 6 month visit in the first year). Setting: The EPAD Trial Delivery Network comprises currently 21 centres across Europe. Participants: Research participants are included if they are over 50 years old and do not have a diagnosis of dementia. Measurements: All research participants undergo multiple assessments to fully characterise the biology of Alzheimer’s disease and relate this to risk factors (both fixed and modifiable) and biomarker expression of disease through brain imaging, fluid samples (CSF, blood, urine and saliva), cognitive performance, functional abilities and neuropsychiatric symptomatology. Results: V500.0 represents the first 500 research participants baselined into EPAD LCS. The mean age was 66.4 (SD=6.7) and 47.8% were male. The data was split for presentation into 4 groups: [1] CDR=0 and Amyloid + (preclinical AD), [2] CDR=0 and Amyloid –, [3] CDR=0.5 and Amyloid + (prodromal AD) and [4] CDR=0.5 and Amyloid -. Conclusions: The EPAD LCS is achieving its primary objective of trial readiness and the structured approach to data release as manifest by this first data release of V500.0 will assist researchers to describe and compare their findings as well as in systematic reviews and meta-analyses. It is anticipated given current recruitment rates that V1500.0 data release will take place in Autumn 2019. V500.1 (when the 1 year follow up is completed on the V500.0 (sub)cohort will be in Autumn 2019 also.

CITATION:
C.W. Ritchie ; G. Muniz-Terrera ; M. Kivipelto ; A. Solomon ; B. Tom ; J.L. Molinuevo ; On Behalf of the EPAD Consortium (2019): The European Prevention of Alzheimer’s Dementia (EPAD) Longitudinal Cohort Study: Baseline Data Release V500.0. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2019.46

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ASSOCIATION OF VITAMIN D LEVELS WITH INCIDENT ALLCAUSE DEMENTIA IN LONGITUDINAL OBSERVATIONAL STUDIES: A SYSTEMATIC REVIEW AND META-ANALYSIS

A. Kalra, A.L. Teixeira, B.S. Diniz

J Prev Alz Dis 2020;7(1):14-20

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Background: The role of vitamin D is not only limited to bone health and pathogenesis of chronic diseases. Evidence now suggests that it is also involved in the development of various dementias and Alzheimer’s disease (AD). Objective: To carry out a systematic review and meta-analysis to evaluate the association between vitamin D levels and increased risk of incident all-cause dementia in longitudinal studies. Design: We conducted a systematic review and meta-analysis using the electronic bibliographic databases PubMed and Scopus. Setting: Prospective cohort studies. Participants: Community-dwelling older adults. Measurements: Vitamin D serum concentrations were categorized in three groups: normal levels (>50 nmol/L), insufficient levels (25 - 49.9 nmol/L), and deficient levels (<25 nmol/L). We performed a meta-analysis using the general inverse variance method to calculate the pooled risk of AD and all-cause dementia according to vitamin D levels. Random-effects or fixed-effect model were used to calculate the pooled risk based on the heterogeneity analysis. Results: Five studies were included in the meta-analysis. The pooled risk of all-cause dementia and AD was significantly higher in those with deficient serum vitamin D level compared to those with normal level (1.33, CI95% [1.15, 1.54], and 1.87, CI95% [1.03, 3.41], respectively). Those with insufficient level also had a higher pooled risk of all-cause dementia and AD, but the strength of association was less robust (1.14 CI95% [1.02, 1.27] and 1.25, CI95% [1.04 - 1.51], respectively). Conclusion: We found a gradient effect for the risk of all-cause dementia and AD according to the vitamin D level, with higher risk in those in the deficient levels group and intermediate risk in those with insufficient levels. Our findings were limited by the relatively small number of studies included in the meta-analysis and their geographic restriction.

CITATION:
A. Kalra ; A.L. Teixeira ; B.S. Diniz (2019): Association of Vitamin D Levels with Incident All-Cause Dementia in Longitudinal Observational Studies: A Systematic Review and Meta-analysis. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2019.44

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LONGITUDINAL COMPARISON OF IN CLINIC AND AT HOME ADMINISTRATION OF THE COGSTATE BRIEF BATTERY AND DEMONSTRATED PRACTICE EFFECTS IN THE MAYO CLINIC STUDY OF AGING

N.H. Stricker, E.S. Lundt, E.C. Alden, S.M. Albertson, M.M. Machulda, W.K. Kremers, D.S. Knopman, R.C. Petersen, M.M. Mielke

J Prev Alz Dis 2020;7(1):21-28

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Background: The Cogstate Brief Battery (CBB) is a computerized cognitive assessment that can be completed in clinic or at home. Design/Objective: This retrospective study investigated whether practice effects / performance trajectories of the CBB differ by location of administration. Participants/Setting: Participants included 1439 cognitively unimpaired individuals age 50-75 at baseline participating in the Mayo Clinic Study of Aging (MCSA), a population-based study of cognitive aging. Sixty three percent of participants completed the CBB in clinic only and 37% completed CBB both in clinic and at home. Measurements: The CBB consists of four subtests: Detection, Identification, One Card Learning, and One Back. Linear mixed effects models were used to evaluate performance trajectories in clinic and at home. Results: Results demonstrated significant practice effects between sessions 1 to 2 for most CBB measures. Practice effects continued over subsequent testing sessions, to a lesser degree. Average practice effects/trajectories were similar for each location (home vs. clinic). One Card Learning and One Back accuracy performances were lower at home than in clinic, and this difference was large in magnitude for One Card Learning accuracy. Participants performed faster at home on Detection reaction time, although this difference was small in magnitude. Conclusions: Results suggest the location where the CBB is completed has an important impact on performance, particularly for One Card Learning accuracy, and there are practice effects across repeated sessions that are similar regardless of where testing is completed.

CITATION:
N.H. Stricker ; E.S. Lundt ; E.C. Alden ; S.M. Albertson ; M.M. Machulda ; W.K. Kremers ; D.S. Knopman ; R.C. Petersen ; M.M. Mielke (2019): Longitudinal Comparison of in Clinic and at Home Administration of the Cogstate Brief Battery and Demonstrated Practice Effects in the Mayo Clinic Study of Aging. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2019.35

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Brief Report

MULTIDOMAIN INTERVENTIONS TO PREVENT COGNITIVE IMPAIRMENT, ALZHEIMER’S DISEASE, AND DEMENTIA: FROM FINGER TO WORLD-WIDE FINGERS

A. Rosenberg, F. Mangialasche, T. Ngandu, A. Solomon, M. Kivipelto

J Prev Alz Dis 2020;7(1):29-36

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Alzheimer’s disease (AD) and dementia are a global public health priority, and prevention has been highlighted as a pivotal component in managing the dementia epidemic. Modifiable risk factors of dementia and AD include lifestyle-related factors, vascular and metabolic disorders, and psychosocial factors. Randomized controlled clinical trials (RCTs) are needed to clarify whether modifying such factors can prevent or postpone cognitive impairment and dementia in older adults. Given the complex, multifactorial, and heterogeneous nature of late-onset AD and dementia, interventions targeting several risk factors and mechanisms simultaneously may be required for optimal preventive effects. The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) is the first large, long-term RCT to demonstrate that a multidomain lifestyle-based intervention ameliorating vascular and lifestyle-related risk factors can preserve cognitive functioning and reduce the risk of cognitive decline among older adults at increased risk of dementia. To investigate the multidomain intervention in other populations and diverse cultural and geographical settings, the World-Wide FINGERS (WW-FINGERS) network was recently launched (https://alz.org/wwfingers). Within this network, new FINGER-type trials with shared core methodology, but local culture and context-specific adaptations, will be conducted in several countries. The WW-FINGERS initiative facilitates international collaborations, provides a platform for testing multidomain strategies to prevent cognitive impairment and dementia, and aims at generating high-quality scientific evidence to support public health and clinical decision-making. Furthermore, the WW-FINGERS network can support the implementation of preventive strategies and translation of research findings into practice.

CITATION:
A. Rosenberg ; F. Mangialasche ; T. Ngandu ; A. Solomon ; M. Kivipelto (2019): Multidomain Interventions to Prevent Cognitive Impairment, Alzheimer’s Disease, and Dementia: From FINGER to World-Wide FINGERS. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2019.41

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ASSOCIATIONS OF LATER-LIFE EDUCATION, THE BDNF VAL66MET POLYMORPHISM AND COGNITIVE CHANGE IN OLDER ADULTS

D.D. Ward, M.J. Summers, M.J. Valenzuela, V.K. Srikanth, J.J. Summers, A.E. King, K. Ritchie, A.L. Robinson, J.C. Vickers

J Prev Alz Dis 2020;7(1):37-42

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In 358 participants of the Tasmanian Healthy Brain Project, we quantified the cognitive consequences of engaging in varying loads of university-level education in later life, and investigated whether or not BDNF Val66Met affected outcomes. Assessment of neuropsychological, health, and psychosocial function was undertaken at baseline, 12-month, and 24-month follow-up. Education load was positively associated with change in language processing performance, but this effect did not reach statistical significance (P = 0.064). The BDNF Val66Met polymorphism significantly moderated the extent to which education load was associated with improved language processing (P = 0.026), with education load having a significant positive relationship with cognitive change in BDNF Met carriers but not in BDNF Val homozygotes. In older adults who carry BDNF Met, engaging in university-level education improves language processing performance in a load-dependent manner.

CITATION:
D.D. Ward ; M.J. Summers ; M.J. Valenzuela ; V.K. Srikanth ; J.J. Summers ; A.E. King ; K. Ritchie ; A.L. Robinson ; J.C. Vickers (2019): Associations of Later-Life Education, the BDNF Val66Met Polymorphism and Cognitive Change in Older Adults. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2019.40

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THE PATIENT IN YOUR ALZHEIMER’S DISEASE STUDY MAY BE IN ANOTHER: DUPLICATION AND DECEPTION IN CLINICAL TRIALS OF ALZHEIMER’S DISEASE

T. Shiovitz, B. Steinmiller, C. Steinmetz, S. Perez, R. Oseas

J Prev Alz Dis 2020;7(1):43-46

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Duplicate and deceptive subjects, a significant issue in CNS studies, are not often considered in Alzheimer’s Disease (AD) clinical trials. However, AD patients and their study partners may be motivated to take advantage of different mechanisms of action, increase odds of receiving active treatment, and/or obtain financial compensation, which may lead them to participate in multiple studies. CTSdatabase reviewed memory loss subjects (n=1087) from January 2017 through May 2019 to determine how many attempted to screen at multiple sites. 117 subjects (10.8%) visited more than one site within two years. When these potential AD subjects went to additional sites, it was predominantly for non-memory indications (often MDD or schizophrenia). For those that participated in studies, the rate of duplication approached 4% of screened AD subjects. This data indicates that significant numbers of AD subjects attempt to enroll at multiple sites, which confounds efficacy and safety signals in clinical trials.

CITATION:
T. Shiovitz ; B. Steinmiller ; C. Steinmetz ; S. Perez ; R. Oseas (2020): The Patient in Your Alzheimer’s Disease Study May be in Another: Duplication and Deception in Clinical Trials of Alzheimer’s Disease. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2020.3

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Review Articles

HEALTH LITERACY IN INDIVIDUALS AT RISK FOR ALZHEIMER’S DEMENTIA: A SYSTEMATIC REVIEW

A. Rostamzadeh, J. Stapels, A. Genske, T. Haidl, S. Jünger, M. Seves, C. Woopen, F. Jessen

J Prev Alz Dis 2020;7(1):47-55

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Background: Health literacy (HL) refers to the capacity to access, understand, appraise and apply information for decision-making and acting in health-related matters. In the field of Alzheimer’s disease (AD), expanding technologies of early disease detection, disease course prediction and eventually personalized prevention confront individuals at-risk with increasingly complex information, which demand substantial HL skills. Here we report current findings of HL research in at-risk groups. Methods: Search strings, referring to HL, AD, amyloid and risk, were developed. A systematic review was conducted in PUBMED, Cochrane Library, PsycINFO, and Web of Science to summarize the state of evidence on HL in at-risk individuals for Alzheimer’s dementia. Eligible articles needed to employ a validated tool for HL, mention the concept or one dimension (access, understand, appraise and apply information for decision-making and acting). Results: 26 quantitative and 9 qualitative studies addressing at least one dimension of HL were included. Overall, there is evidence for a wish to gain knowledge about the own brain status and risk of dementia. Psychological distress may occur and the subjective benefit-risk estimation may be modified after risk disclosure. Effects on lifestyle and planning may occur. Overall understanding and appraisal of information related to AD risk seem variable with several impacting factors. In mild cognitive impairment (MCI) basic HL skill seem to be affected by cognitive dysfunction. Conclusions: Systematic assessment of HL in at-risk population for AD is sparse. Findings indicate the paramount importance of adequate communication with persons at risk, being sensitive to individual needs and preferences. Substantial research needs were identified.

CITATION:
A. Rostamzadeh ; J. Stapels ; A. Genske ; T. Haidl ; S. Jünger ; M. Seves ; C. Woopen ; F. Jessen (2019): Health Literacy in Individuals at Risk for Alzheimer’s Dementia: A Systematic Review. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2019.34

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REVISITING THE HALLMARKS OF AGING TO IDENTIFY MARKERS OF BIOLOGICAL AGE

F. Guerville, P. De Souto Barreto, I. Ader, S. Andrieu, L. Casteilla, C. Dray, N. Fazilleau, S. Guyonnet, D. Langin, R. Liblau, A. Parini, P. Valet, N. Vergnolle, Y. Rolland, B. Vellas

J Prev Alz Dis 2020;7(1):56-64

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The Geroscience aims at a better understanding of the biological processes of aging, to prevent and/or delay the onset of chronic diseases and disability as well as to reduce the severity of these adverse clinical outcomes. Geroscience thus open up new perspectives of care to live a healthy aging, that is to say without dependency. To date, life expectancy in healthy aging is not increasing as fast as lifespan. The identification of biomarkers of aging is critical to predict adverse outcomes during aging, to implement interventions to reduce them, and to monitor the response to these interventions. In this narrative review, we gathered information about biomarkers of aging under the perspective of Geroscience. Based on the current literature, for each hallmark of biological aging, we proposed a putative biomarker of healthy aging, chosen for their association with mortality, age-related chronic diseases, frailty and/or functional loss. We also discussed how they could be validated as useful predictive biomarkers.

CITATION:
F. Guerville ; P. De Souto Barreto ; I. Ader ; S. Andrieu ; L. Casteilla ; C. Dray ; N. Fazilleau ; S. Guyonnet ; D. Langin ; R. Liblau ; A. Parini ; P. Valet ; N. Vergnolle ; Y. Rolland ; B. Vellas (2019): Revisiting the Hallmarks of Aging to Identify Markers of Biological Age. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2019.50

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