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SHORT-TERM PRACTICE EFFECTS AND AMYLOID DEPOSITION: PROVIDING INFORMATION ABOVE AND BEYOND BASELINE COGNITION

K. Duff, D.B. Hammers, B.C.A. Dalley, K.R. Suhrie, T.J. Atkinson, K.M. Rasmussen, K.P. Horn, B.E. Beardmore, L.D. Burrell, N.L. Foster, J. M. Hoffman

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Background: Practice effects, which are improvements in cognitive test scores due to repeated exposure to testing materials, may provide information about Alzheimer’s disease pathology, which could be useful for clinical trials enrichment. Objectives: The current study sought to add to the limited literature on short-term practice effects on cognitive tests and their relationship to amyloid deposition on neuroimaging. Participants: Twenty-seven, non-demented older adults (9 cognitively intact, 18 with mild cognitive impairment) received amyloid imaging with 18F-Flutemetamol, and two cognitive testing sessions across one week to determine practice effects. Results: A composite measure of 18F-Flutemetamol uptake correlated significantly with all seven cognitive tests scores on the baseline battery (r’s = -0.61 – 0.59, all p’s<0.05), with higher uptake indicating poorer cognition. Practice effects significantly added to the relationship (above and beyond the baseline associations) with 18F-Flutemetamol uptake on 4 of the 7 cognitive test scores (partial r’s = -0.45 – 0.44, p’s<0.05), with higher uptake indicating poorer practice effects. The odds ratio of being “amyloid positive” was 13.5 times higher in individuals with low practice effects compared to high practice effects. Conclusions: Short-term practice effects over one week may be predictive of progressive dementia and serve as an affordable screening tool to enrich samples for preventative clinical trials in Alzheimer’s disease.

CITATION:
K. Duff ; D.B. Hammers ; B.C.A. Dalley ; K.R. Suhrie ; T.J. Atkinson ; K.M. Rasmussen ; K.P. Horn ; B.E. Beardmore ; L.D. Burrell ; N.L. Foster ; J. M. Hoffman (2017): Short-Term Practice Effects and Amyloid Deposition: Providing Information Above and Beyond Baseline Cognition. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2017.9

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THE ROSAS COHORT: A PROSPECTIVE, LONGITUDINAL STUDY OF BIOMARKERS FOR ALZHEIMER’S DISEASE. STRATEGY, METHODS AND INITIAL RESULTS

A. de Mauléon, M. Soto, V. Kiyasova, J. Delrieu, I. Guignot, S. Galtier, M. Lilamand, C. Cantet, F. Lala, N. Sastre, S. Andrieu, M. Pueyo, P.J. Ousset, B. Vellas

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Objective: The aims of the Research Of biomarkers in Alzheimer’s diseaSe (ROSAS) study were to determine the biofluid and imaging biomarkers permitting an early diagnosis of Alzheimer’s disease and better characterisation of cognitive and behavioural course of the pathology. This paper outlines the overall strategy, methodology of the study, baseline characteristics of the population and first longitudinal results from the ROSAS cohort. Methods: Longitudinal prospective monocentric observational study performed at the Alzheimer’s disease Research centre in Toulouse. A total of 387 patients were studied and analyzed in 3 groups: 184 patients with dementia of Alzheimer’s type, 96 patients with memory disorders without dementia (Mild Cognitive Impairment) and 107 patients without abnormal memory tests (control group), and were followed up during 4 years. Patient’s sociodemographic characteristics, risk factors, medical conditions, previous and current medications, neuropsychological assessment and overall cognitive status were recorded. Blood and urine samples were collected at every year, Magnetic Resonance Imaging were performed at inclusion, after one year of follow-up and at the end of the study. Results: At baseline, three different groups of the cohort differed interestingly in age, level of education, and in percentage of ApoEε4 carriers whereas the history of cardiovascular and endocrine pathologies were similar among the groups. During the follow-up period (3-4 years) 42 mild cognitive impairment patients (43.8%) progressed to dementia, 7 controls progressed into mild cognitive impairment and 1 patient in the control group converted from mild cognitive impairment group to dementia of Alzheimer’s type group. During the first year of follow up, the incidence of progression from mild cognitive impairment to dementia of Alzheimer’s type was 12.7 per 100, during the second year 33.9 per 100 and 46.7 per 100 for the third year. Conclusion: This paper presents the baseline characteristics of the unique French prospective monocenter study in which the natural course of dementia of Alzheimer’s type was evaluated. Future analysis of blood and urine samples collection from the ROSAS study will permit to identify possible biofluid biomarkers predicting the early stages of the dementia of Alzheimer’s type and risk of progression from Mild Cognitive Impairment to Alzheimer’s disease.

CITATION:
A. de Mauléon ; M. Soto ; V. Kiyasova ; J. Delrieu ; I. Guignot ; S. Galtier ; M. Lilamand ; C. Cantet ; F. Lala ; N. Sastre ; S. Andrieu ; M. Pueyo ; P.J. Ousset ; B. Vellas (2017): The ROSAS Cohort: A Prospective, Longitudinal Study of Biomarkers for Alzheimer’s Disease. Strategy, Methods and Initial Results. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2017.8

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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

X. Zhang, F.A. Schmitt, A.M. Caban-Holt, X. Ding, R.J. Kryscio, E. Abner

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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.

CITATION:
X. Zhang ; F.A. Schmitt ; A.M. Caban-Holt ; X. Ding ; R.J. Kryscio ; E. Abner (2017): 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. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2017.7

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CTAD 2016 abstract: EXPEDITION3: A PHASE 3 TRIAL OF SOLANEZUMAB IN MILD DEMENTIA DUE TO ALZHEIMER’S DISEASE

L.S. Honig, A. Hake, K. Sundell, C. Carlson, V. Poole Hoffmann, M. Case, H. Liu-Seifert, R. Dean, R. DeMattos, M. Mintun, R. Khanna, K.J. Selzler, E. Siemers

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Background: Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by amyloid beta (Aβ) plaques, neurofibrilliary tangles, and neuronal loss with clinical symptoms including cognitive and functional impairment. Solanezumab, a humanized monoclonal antibody, was studied to determine if it would slow the progression of AD by increasing clearance of soluble Aβ from the brain. Methods: EXPEDITION3 was a double-blind, placebo-controlled, Phase 3 global study conducted in 11 countries at 210 sites in patients age 55 to 90 years with mild dementia due to AD (mild AD) (Mini–Mental State Examination [MMSE] score of 20 through 26), with confirmed amyloid pathology based on biomarkers (amyloid positive by F18 florbetapir PET or CSF Aβ1-42), with an optional open-label extension. Patients were randomized to 400-mg solanezumab (N=1057) or placebo (N=1072) administered intravenously every 4 weeks. The primary efficacy outcome was change on the 14-item Alzheimer’s Disease Assessment Scale-Cognitive subscale (ADAS-Cog14) from baseline to Week 80. Key functional measures assessed included the Instrumental activities of the Alzheimer’s Disease Cooperatives Study Activities of Daily Living Inventory (ADCS-iADL) and the Functional Activities Questionnaire (FAQ). Additional efficacy measures assessed included the MMSE and the Clinical Dementia Rating scale–Sum of Boxes (CDR-SB). Key safety assessments included adverse event (AE) reporting and magnetic resonance imaging (MRI). Biomarkers included plasma changes in Aβ1-40 and Aβ1-42, CSF changes in total and phosphorylated tau (p-tau), and neuroimaging measures including positron emission tomography (PET) scans using florbetapir F18 and F18 flortaucipir, and volumetric MRI. Results: There was no statistically significant difference between treatment groups for the primary endpoint, ADAS-Cog14 (p=.095); numerically there was 11% less decline in cognition in the solanezumab-treated group compared with placebo. For the key secondary endpoints, treatment effects favoring solanezumab were seen on cognitive and functional measures, including 13% less decline on the MMSE (p=.014), 15% less decline on the CDR-SB (p=.004), and 14% less decline on the ADCS-iADL (p=.019). FAQ did not show statistically significant differences (7% less decline, p=.140). Solanezumab-treated patients showed a statistically significant greater increase in plasma Aβ1-40 and Aβ1-42 compared with placebo-treated patients (p<.001 for each biomarker), confirming peripheral target engagement. Changes between treatment groups for florbetapir PET, CSF total tau and p-tau, and flortaucipir PET did not show significant treatment differences. Whole brain atrophy and ventricular enlargement were not statistically different between treatment groups, as demonstrated by volumetric MRI. Safety findings were comparable across study treatment groups with respect to deaths, serious AEs (SAEs), discontinuations due to an AE and treatment-emergent AEs (TEAEs). There were few statistically significant treatment group differences at the individual Preferred Term level for TEAEs and none for any SAEs. Conclusions: EXPEDITION3, a Phase 3 trial of solanezumab initiated in a mild AD patient population, did not meet the primary objective of decreasing cognitive decline. Several secondary clinical endpoints, including both cognitive and functional measures, directionally favored solanezumab, but the effect sizes were small. Factors possibly relevant to interpretation of the study results include drug target, disease stage studied, and drug dosage delivered. Solanezumab had a favorable safety profile at the dose studied.

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SEX AND AGE DIFFERENCES IN THE ASSOCIATION OF BLOOD PRESSURE AND HYPERTENSION WITH COGNITIVE FUNCTION IN THE ELDERLY: THE RANCHO BERNARDO STUDY

D. Kritz-Silverstein, G.A. Laughlin, L.K. McEvoy, E. Barrett-Connor

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Objectives: This study examines sex and age differences in associations of systolic and diastolic blood pressure (SBP, DBP), pulse pressure and hypertension with cognitive function in a community-dwelling population. Design: Cross-sectional study. Setting: Research clinic visit in 1988-91. Participants: Participants were 693 men and 1022 women aged 50-97 Measurements: Blood pressure was measured and 12 cognitive function tests were administered. Results: Average age was 73.8±9.9 in men and 73.2±9.3 in women; 62.6% of men and 63.4% of women were hypertensive (SBP≥140 mmHg, DBP≥90 mmHg, or antihypertensive medication use). Each 5-unit increment in SBP, DBP, or pulse pressure and categorical hypertension was associated with significantly increased odds of poor verbal fluency performance in men and poor Trails B performance in women, with strongest associations for hypertension (OR=1.97, CI:1.01,3.85 in men; OR=1.51, CI:1.01,2.26 in women). After age stratification, associations remained statistically significant in younger (<80 years ) but not older (≥80 years) participants. Conclusion: Blood pressure as a continuous or categorical variable was associated with poor performance on cognitive function tests, but domains varied by sex and associations were found only in those younger than 80 years. The absent associations in those aged 80 years and older could support the hypothesis that increased blood flow is required to maintain cerebral perfusion with advancing age, or could reflect a survivor effect.

CITATION:
D. Kritz-Silverstein ; G.A. Laughlin ; L.K. McEvoy ; E. Barrett-Connor (2017): Sex and Age Differences in the Association of Blood Pressure and Hypertension with Cognitive Function in the Elderly: The Rancho Bernardo Study. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2017.6

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ETHICAL ISSUES IN THE DEVELOPMENT OF READINESS COHORTS IN ALZHEIMER’S DISEASE RESEARCH

R. Milne, E. Bunnik, K. Tromp, S. Bemelmans, S. Badger, D.Gove, M. Maman, M. Schermer, L. Truyen, C. Brayne, E. Richard

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There is growing interest in the development of novel approaches to secondary prevention trials in Alzheimer’s disease to facilitate screening and recruitment of research participants and to reduce the time and costs associated with clinical trials. Several international research collaborations are setting up research infrastructures that link existing research cohorts, studies or patient registries to establish ‘trial-ready’ or ‘readiness’ cohorts. From these cohorts, individuals are recruited into clinical trial platforms. In setting up such research infrastructures, researchers must make ethically challenging design decisions in at least three areas: re-contacting participants in existing research studies, obtaining informed consent for participation in a readiness cohort, and disclosure of Alzheimer’s disease-related biomarkers. These ethical considerations have been examined by a dedicated workgroup within the European Prevention of Alzheimer’s Dementia (EPAD) project, a trans-European longitudinal cohort and adaptive proof-of-concept clinical trial platform. This paper offers recommendations for the ethical management of re-contact, informed consent and risk disclosure which may be of value to other research collaborations in the process of developing readiness cohorts for prevention trials in Alzheimer’s disease and other disease areas.

CITATION:
R. Milne ; E. Bunnik ; K. Tromp ; S. Bemelmans ; S. Badger ; D. Gove ; M. Maman ; M. Schermer ; L. Truyen ; C. Brayne ; E. Richard (2017): Ethical Issues in the Development of Readiness Cohorts in Alzheimer’s Disease Research. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2017.5

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OBJECTIVE COGNITIVE IMPAIRMENT AND PROGRESSION TO DEMENTIA IN WOMEN: THE PROSPECTIVE EPIDEMIOLOGICAL RISK FACTOR STUDY

J. Skov Neergaard, K. Dragsbæk, C. Christiansen, M. Asser Karsdal, S. Brix, K. Henriksen

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Background: Identification of subjects with a progressive disease phenotype is an urgent need in the pharmaceutical industry where most of the recent clinical trials in Alzheimer’s disease have failed. Objectives: The objective of this study was to identify subgroups of individuals with objective cognitive impairment (OCI), who were most likely to progress to dementia and to identify the risk factors associated with progression. Design: Prospective cohort study. Setting: Population-based. Participants: 5,380 elderly women from Denmark. Measurements: The Short Blessed Test and a category fluency test with animal naming, was used to assess cognitive function, and to classify them into different groups of OCI. Results: OCI was identified in 852 subjects at baseline. The risk of dementia was elevated for OCI subjects as compared to subjects with normal cognition (HR 1.46[1.19-1.79]). The courses of OCI were studied in a sub-cohort who completed the cognitive assessment at both the baseline and the follow-up visit (n = 1,933). Of these subjects 203 had OCI at baseline. The multi-domain subtypes of OCI were associated with progressive OCI. Subjects most likely to progress were older, physically inactive, had a higher level of total cholesterol (>6.5 mmol/L) and had a history of depression as compared to subjects with a non-progressive course of OCI. Conclusions: In this cohort we identified a risk profile associated with progression from OCI in older women. The degree of impairment at baseline was an important predictor of conversion to dementia, additionally several modifiable risk factors were associated with progression.

CITATION:
J. Skov Neergaard ; K. Dragsbæk ; C. Christiansen ; M. Asser Karsdal ; S. Brix ; K. Henriksen (2017): Objective Cognitive Impairment and Progression to Dementia in Women: The Prospective Epidemiological Risk Factor Study. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2017.4

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FROM BRAIN DISEASE TO BRAIN HEALTH: PRIMARY PREVENTION OF ALZHEIMER’S DISEASE AND RELATED DISORDERS IN A HEALTH SYSTEM USING AN ELECTRONIC MEDICAL RECORD-BASED APPROACH

A.M. Fosnacht, S. Patel, C. Yucus, A. Pham, E. Rasmussen, R. Frigerio, S. Walters, D. Maraganore

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Background: Alzheimer’s disease and aging brain disorders are progressive, often fatal neurodegenerative diseases. Successful aging, modern lifestyles and behaviors have combined to result in an expected epidemic. Risks for these diseases include genetic, medical, and lifestyle factors; over 20 modifiable risks have been reported. Objectives: We aim to primarily prevent Alzheimer’s disease and related disorders through electronic medical record (EMR)-based screening, risk assessments, interventions, and surveillance. Design: We identified modifiable risks; developed human, systems and infrastructural resources; developed interventions; and targeted at-risk groups for the intervention. Setting: A Community Based Health System. Participants: In year one (June 2015 to May 2016), 133 at-risk patients received brain health services with the goal of delaying or preventing Alzheimer’s disease and related disorders. Measurements: We created mechanisms to identify patients at high risk of neurodegenerative disease; EMR-based structured clinical documentation support tools to evaluate risk factors and history; evidence-based interventions to modify risk; and the capacity for annual surveillance, pragmatic trials, and practice-based and genomic research using the EMR. Results: This paper describes our Center for Brain Health, our EMR tools, and our first year of healthy but at-risk patients. Conclusion: We are translating research into primary prevention of Alzheimer’s disease and related disorders in our health system and aim to shift the paradigm in Neurology from brain disease to brain health.

CITATION:
A.M. Fosnacht ; S. Patel ; C. Yucus ; A. Pham ; E. Rasmussen ; R. Frigerio ; S. Walters ; D. Maraganore (2017): From Brain Disease to Brain Health: Primary Prevention of Alzheimer’s Disease and Related Disorders in a Health System Using an Electronic Medical Record-Based Approach. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2017.3

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DEPENDENCE LEVELS AS INTERIM CLINICAL MILESTONES ALONG THE CONTINUUM OF ALZHEIMER’S DISEASE: 18-MONTH RESULTS FROM THE GERAS OBSERVATIONAL STUDY

K. Kahle-Wrobleski, J.S. Andrews, M. Belger, W. Ye, S. Gauthier, D.M. Rentz, D. Galasko

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Background: While functional loss forms part of the current diagnostic criteria used to identify dementia due to Alzheimer’s disease, the gradual and progressive nature of the disease makes it difficult to recognize clinically relevant signposts that could be helpful in making treatment and management decisions. Having previously observed a significant relationship between stages of functional dependence (the level of assistance patients require consequent to Alzheimer’s disease deficits, derived from the Alzheimer’s Disease Cooperative Study – Activities of Daily Living Scale) and cognitive severity, we investigated whether measures of functional dependence could be utilized to identify clinical milestones of Alzheimer’s disease progression. OBJECTIVES: To describe the patterns of change in dependence over the course of 18 months in groups stratified according to cognitive Alzheimer’s disease dementia severity (determined using the Mini-Mental State Examination score) and to identify characteristics associated with patients showing worsening dependence (progressors) versus those showing no change or improvement (non-progressors). DESIGN: Analysis of longitudinal data from the GERAS study. SETTING: GERAS is an 18-month prospective, multicenter, naturalistic, observational cohort study reflecting the routine care of patients with Alzheimer’s disease in France, Germany, and the United Kingdom. PARTICIPANTS: 1495 community-living patients, aged ≥55 years, diagnosed with probable Alzheimer’s disease dementia, and their caregivers. MEASUREMENTS: Dependence levels, cognitive function, behavioral symptoms, caregiver burden, and cost were assessed at baseline and at 18 months. RESULTS: Of 971 patients having both baseline and 18-month data, 42% (408) were progressors and 563 (58%) were non-progressors. This general pattern held for all three levels of baseline Alzheimer’s disease dementia severity – mild (Mini-Mental State Examination score 21–26), moderate (15–20) or moderately severe/severe (<15) – with 40–45% of each group identified as progressors and 55–60% as non-progressors. No baseline differences were seen between progressors and non-progressors in cognitive scores or behavioral symptoms, although progressors had significantly shorter times since diagnosis and showed milder functional impairment. Baseline factors predictive of increasing dependence over 18 months included more severe cognitive impairment, living with others, and having multiple caregivers. A higher level of initial dependence was associated with less risk of dependence progression. Total societal costs of care also increased with greater dependence. CONCLUSIONS: In this large cohort, 42% of Alzheimer’s disease dementia patients at all levels of cognitive severity became more dependent within 18 months of observation while 58% did not progress. Dependence levels may be considered as meaningful interim clinical milestones that reflect Alzheimer’s disease-related functional deficits, although a time frame that extends beyond 18 months may be necessary to observe changes if used in clinical trials or other longitudinal studies. Recognition of predictors of greater dependence offers opportunities for intervention.

CITATION:
K. Kahle-Wrobleski ; J.S. Andrews ; M. Belger ; W. Ye ; S. Gauthier ; D.M. Rentz ; D. Galasko (2017): Dependence Levels as Interim Clinical Milestones Along the Continuum of Alzheimer’s Disease: 18-Month Results from the GERAS Observational Study. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2017.2

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FACEHBI: A PROSPECTIVE STUDY OF RISK FACTORS, BIOMARKERS AND COGNITION IN A COHORT OF INDIVIDUALS WITH SUBJECTIVE COGNITIVE DECLINE. STUDY RATIONALE AND RESEARCH PROTOCOLS

O. Rodriguez-Gomez, A. Sanabria, A. Perez-Cordon, D. Sanchez-Ruiz, C. Abdelnour, S. Valero, I. Hernandez, M. Rosende-Roca, A. Mauleon, L. Vargas, M. Alegret, A. Espinosa, G. Ortega, M. Guitart, A. Gailhajanet, O. Sotolongo-Grau, S. Moreno-Grau, S. Ruiz, M. Tarragona, J. Serra, E. Martin, E. Peleja, F. Lomeña, F. Campos, A. Vivas, M.Gomez-Chiari, M.A. Tejero, J. Giménez, P. Pesini, M. Sarasa, G.Martinez, A. Ruiz, L. Tarraga, M.Boada

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Background: Long-term longitudinal studies with multimodal biomarkers are needed to delve into the knowledge of preclinical AD. Subjective cognitive decline has been proposed as a risk factor for the development of cognitive impairment. Thus, including individuals with SCD in observational studies may be a cost-effective strategy to increase the prevalence of preclinical AD in the sample. Objectives: To describe the rationale, research protocols and baseline characteristics of participants in the Fundació ACE Healthy Brain Initiative (FACEHBI). Design: FACEHBI is a clinical trial (EudraCT: 2014-000798-38) embedded within a long-term observational study of individuals with SCD. Setting: Participants have been recruited at the memory clinic of Fundació ACE (Barcelona) from two different sources: patients referred by a general practitioner and individuals from an Open House Initiative. Participants: 200 individuals diagnosed with SCD with a strictly normal performance in a comprehensive neuropsychological battery. Measurements: Individuals will undergo an extensive neuropsychological protocol, risk factor assessment and a set of multimodal biomarkers including florbetaben PET, structural and functional MRI, diffusion tensor imaging, determination of amyloid species in plasma and neurophthalmologic assessment with optical coherence tomography. Results: Two hundred individuals have been recruited in 15 months. Mean age was 65.9 years; mean MMSE was 29.2 with a mean of 14.8 years of education. Conclusions: FACEHBI is a long-term study of cognition, biomarkers and lifestyle that has been designed upon an innovative symptom-based approach using SCD as target population. It will shed light on the pathophysiology of preclinical AD and the role of SCD as a risk marker for the development of cognitive impairment.

CITATION:
O. Rodriguez-Gomez ; A. Sanabria ; A. Perez-Cordon ; D. Sanchez-Ruiz ; C. Abdelnour ; S. Valero ; I. Hernandez ; M. Rosende-Roca ; A. Mauleon ; L. Vargas ; M. Alegret ; A. Espinosa ; G. Ortega ; M. Guitart ; A. Gailhajanet ; O. Sotolongo-Grau ; S. Moreno-Grau ; S. Ruiz ; M. Tarragona ; J. Serra ; E. Martin ; E. Peleja ; F. Lomeña ; F. Campos ; A. Vivas ; M.Gomez-Chiari ; M.A. Tejero ; J. Giménez ; P. Pesini ; M. Sarasa ; G.Martinez ; A. Ruiz ; L. Tarraga ; M. Boada (2016): FACEHBI: A Prospective Study of Risk Factors, Biomarkers and Cognition in a Cohort of Individuals with Subjective Cognitive Decline. Study Rationale and Research Protocols. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2016.122

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ALBUMIN, HEMOGLOBIN, AND THE TRAJECTORY OF COGNITIVE FUNCTION IN COMMUNITY-DWELLING OLDER JAPANESE: A 13-YEAR LONGITUDINAL STUDY

H. Murayama, S. Shinkai, M. Nishi, Y. Taniguchi, H. Amano, S. Seino, Y. Yokoyama, H. Yoshida, Y. Fujiwara, H. Ito

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Background: Cognitive function can substantially decline over a long period, and understanding the trajectory of cognitive function is important. However, little is known about the linkage between nutritional biomarkers and long-term cognitive change. Objectives: We analyzed 13-year longitudinal data for older Japanese to examine the associations of serum albumin and hemoglobin levels with the trajectory of cognitive function. Design: Longitudinal study. Setting: Community-based. Participants: A total of 1,744 community-dwelling adults aged 65 years or older who participated in annual health examinations in Kusatsu town, Gunma Prefecture, Japan, from 2002–2014. Measurements: Cognitive function was assessed annually by the Mini-Mental State Examination (MMSE). Albumin and hemoglobin levels at baseline (the year when a respondent first participated in the health examination) were divided into quartiles. Hierarchical linear modeling was used to analyze intrapersonal and interpersonal differences in cognitive function. Results: Participants’ MMSE scores decreased at an accelerated rate over the 13-year period. Participants with the lowest baseline albumin level (below the first quartile line) showed a greater accelerated decline in MMSE scores over time, compared with those with the highest level (above the third quartile line). Moreover, MMSE scores in participants with a lower hemoglobin level and lower MMSE score at baseline tended to decline faster over time at an accelerated rate. Conclusions: These findings yield new insights about the complex and diverse roles of these nutritional biomarkers on the trajectory of cognitive function in old age.

CITATION:
H. Murayama ; S. Shinkai ; M. Nishi ; Y. Taniguchi ; H. Amano ; S. Seino ; Y. Yokoyama ; H. Yoshida ; Y. Fujiwara ; H. Ito (2016): Albumin, Hemoglobin, and the Trajectory of Cognitive Function in Community-Dwelling Older Japanese: A 13-Year Longitudinal Study. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2016.113

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JPAD Volume 4, N°01 - March 2017

 

Original Research

COMPUTERIZED COGNITIVE TESTING FOR USE IN CLINICAL TRIALS: A COMPARISON OF THE NIH TOOLBOX AND COGSTATE C3 BATTERIES

R.F. Buckley, K.P. Sparks, K.V. Papp, M. Dekhtyar, C. Martin, S. Burnham, R.A. Sperling, D.M. Rentz

J Prev Alz Dis 2017;1:3-11

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Background: As prevention trials for Alzheimer’s disease move into asymptomatic populations, identifying older individuals who manifest the earliest cognitive signs of Alzheimer’s disease is critical. Computerized cognitive testing has the potential to replace current gold standard paper and pencil measures and may be a more efficient means of assessing cognition. However, more empirical evidence about the comparability of novel computerized batteries to paper and pencil measures is required. Objectives: To determine whether two computerized IPad batteries, the NIH Toolbox Cognition Battery and Cogstate-C3, similarly predict subtle cognitive impairment identified using the Preclinical Alzheimer Cognitive Composite (PACC). Design, Setting, Participants: A pilot sample of 50 clinically normal older adults (Mage=68.5 years±7.6, 45% non-Caucasian) completed the PACC assessment, and the NIH Toolbox and Cogstate-C3 at research centers of Massachusetts General and Brigham and Women’s Hospitals. Participants made 3-4 in-clinic visits, receiving the PACC first, then the NIH Toolbox, and finally the Cogstate-C3. Measurements: Performance on the PACC was dichotomized by typical performance (>= 0.5SD), versus subtle cognitive impairment (<0.5SD). Composites for each computerized battery were created using principle components analysis, and compared with the PACC using non-parametric Spearman correlations. Logistic regression analyses were used to determine which composite was best able to classify subtle cognitive impairment from typical performance. Results: The NIH Toolbox formed one composite and exhibited the strongest within-battery alignment, while the Cogstate-C3 formed two distinct composites (Learning-Memory and Processing Speed-Attention). The NIH Toolbox and C3 Learning-Memory composites exhibited positive correlations with the PACC (ρ=0.49, p<0.001; ρ=0.58, p<0.001, respectively), but not the C3 Processing Speed-Attention composite, ρ=-0.18, p=0.22. The C3 Learning-Memory was the only composite that classified subtle cognitive impairment, and demonstrated the greatest sensitivity (62%) and specificity (81%) for that subtle cognitive impairment. Conclusions: Preliminary findings suggest that the NIH Toolbox has the advantage of showing the strongest overall clustering and alignment with standardized paper-and-pencil tasks. By contrast, Learning-Memory tasks within the Cogstate-C3 battery have the greatest potential to identify cross-sectional, subtle cognitive impairment as defined by the PACC.

CITATION:
R.F. Buckley ; K.P. Sparks ; K.V. Papp ; M. Dekhtyar ; C. Martin ; S. Burnham ; R.A. Sperling ; D.M. Rentz (2017): Computerized Cognitive Testing for Use in Clinical Trials: A Comparison of the NIH Toolbox and Cogstate C3 Batteries. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2017.1

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SHORT-TERM IMPACT OF A COMBINED NUTRACEUTICAL ON COGNITIVE FUNCTION, PERCEIVED STRESS AND DEPRESSION IN YOUNG ELDERLY WITH COGNITIVE IMPAIRMENT: A PILOT, DOUBLE-BLIND, RANDOMIZED CLINICAL TRIAL

A.F. Cicero, M. Bove, A. Colletti, M. Rizzo, F. Fogacci, M. Giovannini, C. Borghi

J Prev Alz Dis 2017;1:12-15

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Background: The prevalence of senile dementia is increasing worldwide, especially in the developed countries. Nevertheless, drug therapy isn’t often enough to treat this condition. Researchers are evaluating the possible impact of a preventive approach, based on an improvement of lifestyle and the intake of micronutrients. Moreover, there is an increasing interest for combined nutraceuticals that can act as memory and learning enhancers, with a significant and beneficial potential on the cognitive disorders. Objective: To evaluate the effects of a rational assemblage of nutraceuticals on cognitive functions in a sample of 30 elderly subjects. Design: Double bind, cross-over designed trial versus placebo Setting: outpatient clinical practice Participants: 30 elderly subjects with basal Mini-Mental State Examination score between 20 and 27 and self-perceived cognitive decline. Intervention: Treatment with a combination of nutraceuticals based on Bacopa monnieri, L-theanine, Crocus sativus, copper, folate and vitamins of B and D group. After2 months of treatment or placebo. Measurements: Patients were evaluated with Mini-Mental State Examination (MMSE), Perceived Stress Questionnaire (PSQ) and Index and Self-Rating Depression Scale (SRDS). Results: MMSE and PSQ Index significantly improved in the active treatment arm, both versus baseline and versus the parallel arm. Both groups experienced a significant improving in the SRDS scores. Conclusions: We obtained a good and significant improvement of the cognitive functions tested with the MMSE, PSQ-Index and SRDS score, after 2 months of combined therapy of nutraceuticals. Further confirmation will be needed to verify these observations on the middle and long term in a larger number of subjects.

CITATION:
A.F. Cicero ; M. Bove ; A. Colletti ; M. Rizzo ; F. Fogacci ; M. Giovannini ; C. Borghi (2016): Short-Term Impact of a Combined Nutraceutical on Cognitive Function, Perceived Stress and Depression in Young Elderly with Cognitive Impairment: A Pilot, Double-Blind, Randomized Clinical Trial . The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2016.110

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GINKGO BILOBA EXTRACT CONSUMPTION AND LONG-TERM OCCURRENCE OF DEATH AND DEMENTIA

J.F. Dartigues, L. Grasset, C. Helmer, C. Féart, L. Letenneur, H. Jacqmin-Gadda, P. Joly, H. Amieva

J Prev Alz Dis 2017;1:16-20

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Objectives: To study the benefit of Ginkgo Biloba Extract (GBe) consumption on the long term risk of dementia and death in elderly people. Design: The Paquid study is a population-based cohort with regular follow-up screenings up to twenty-two years and systematic detection of incident cases of dementia. Statistical analysis was conducted with an illness-death model dealing with interval censoring of dementia and competing risk of death. Setting: The sample was randomly selected from electoral rolls in two administrative areas of southwestern France in 1988-1989. Participants: 3,777 subjects aged 65 years or older at baseline who were living at home Measurement: Participants were visited at home by a trained psychologist at baseline in 1988/1989, and then again approximately every two years. Drug consumption for the treatment of cognitive or neurosensory impairment was collected at baseline. Participants were classified as GBe consumers, other drug (OD) consumers and untreated controls (UC) for this motive. Results: After adjustment for sociodemographic factors and cognitive measures at baseline the risk for dementia was not significantly different in GBe consumers and UC (Hazard Ratio (HR)=1.21, 95% Confidence Interval (95% CI)=0.95-1.55, p=0.42) and it was of the same magnitude but significantly increased in the OD group versus UC (HR=1.25, 95% CI=1.06-1.46, p=0.004). With the same adjustment, the risk of dying in non-demented subjects was reduced in GBe consumers versus UC (HR=0.67, 95% CI=0.49-0.93, p=0.02) while it was the same as the reference group in OD consumers. The mean lifetimes without dementia was of 11.2 years in the UC group (95% CI=10.9-11.5), 11.1 years in the GBe group (10.2-11.9) and 9.1 years for the OD group (8.7-9.6). Conclusion: GBe consumers have a lower risk of dying before dementia and a longer lifetime without dementia than participants taking other drugs for the same indication.

CITATION:
J.F. Dartigues ; L. Grasset ; C. Helmer ; C. Féart ; L. Letenneur ; H. Jacqmin-Gadda ; P. Joly ; H. Amieva (2016): Ginkgo Biloba Extract Consumption and Long-term Occurrence of Death and Dementia. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2016.105

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STIMULUS-LOCKED LATERALIZED READINESS POTENTIAL AND PERFORMANCE: USEFUL MARKERS FOR DIFFERENTIATING BETWEEN AMNESTIC SUBTYPES OF MILD COGNITIVE IMPAIRMENT

S. Cid-Fernández, M. Lindín, F. Díaz

J Prev Alz Dis 2017;1:21-28

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BACKGROUND: The findings of previous studies, in which event-related potentials (ERPs) related to stimulus evaluation were measured, do not fully explain the behavioral decline observed in amnestic mild cognitive impairment (aMCI; prodromal stage of Alzheimer’s Disease). OBJECTIVES: Motor ERPs were evaluated in this study with the aim of discovering complementary explanations and identifying aMCI biomarkers. DESIGN: Cross-sectional study. SETTING: Santiago de Compostela, Galicia, Spain. PARTICIPANTS: Nineteen healthy control (52-81 years old), 21 single-domain aMCI (sdaMCI; 51-87 years old) and 12 multi-domain aMCI (mdaMCI, 62-85 years old) adults. MEASUREMENTS: Reaction times (RTs), percentage of hits, and stimulus-locked and response-locked lateralized readiness potentials (sLRP and rLRP, indexes of response selection and preparation) were evaluated. RESULTS: mdaMCI participants showed longer RTs than control adults and less hits than control and sdaMCI participants. In addition, the mdaMCI group showed lower sLRP amplitudes than the control participants, and the sdaMCI group showed longer sLRP peak latencies. CONCLUSIONS: Control and sdaMCI groups did not differ in relation to RTs or hits, although sLRP peak latencies (sensitivity and specificity >.73) were longer in the sdaMCI group, which may be a sign of compensatory mechanisms or early indication of a decline in motor control. RTs were longer and sLRP amplitudes were smaller in the mdaMCI than in the Control group, and mdaMCI scored fewer hits than control and sdaMCI participants, indicating behavioral and neurocognitive deficits. The combination of hits and RTs discriminated mdaMCI from control adults (sensitivity and specificity >.82); and the combination of sLRP peak latency and hits discriminated mdaMCI from sdaMCI adults (sensitivity=1.00, specificity=.88).

CITATION:
S. Cid-Fernández ; M. Lindín ; F. Díaz (2016): Stimulus-Locked Lateralized Readiness Potential and Performance: Useful Markers for Differentiating between Amnestic Subtypes of Mild Cognitive Impairment. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2016.88

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ASSESSING THE RELATIONSHIP BETWEEN VITAMIN D STATUS AND IMPAIRMENTS IN COGNITIVE AND PHYSICAL PERFORMANCE IN OLDER ADULTS USING A DUAL TASK PHYSICAL PERFORMANCE TEST

J. Lopez, A. Campa, J.E. Lewis, F.G. Huffman, J.P. Liuzzi, T. Li, A.H. Martinez, S.M. Ferris, A. Rasul, A. Farooqi, A.M. Lopez Medrano, S.E. Atlas, E. Tiozzo, J. Konefal, J.M. Woolger

J Prev Alz Dis 2017;1:29-36

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Background: Vitamin D deficiency has been associated with an increased risk of falls in older adults. Several studies have demonstrated an association between vitamin D deficiency and gait and cognitive impairments, which are two risk factors for falls in the elderly. There is lack of research about the role of vitamin D in cognitive function in the context of mobility. Objective: The purpose of this study was to evaluate the association between vitamin D status with the age-related changes in mobility through higher order cognitive function using a dual task physical performance test. Design: Cross-sectional Setting: Community-dwelling older adult population located in Miami, Fl. Participants: Healthy participants over the age of 55 (n=97) who participated in the parent interventional study. Measurements: Participants completed assessments that included serum levels of vitamin D, surveys, and dual task physical performance tests. Spearman’s correlations, independent t-tests, repeated measures ANOVAs and multiple logistic regressions were used to examine the relationship between vitamin D insufficiency (25-hydroxyvitamin D <30 ng/ml) and sufficiency (≥30 ng/ml) and dual task physical performance variables. The significance level was set at α=0.05. Results: There were no significant associations between vitamin D insufficiency and gait velocity during either task. Using Spearman correlations, slower single (P=0.011) and dual task counting rates (P=0.006) were significantly associated with vitamin D insufficiency. Independent t-tests showed dual and single task counting rates were significantly lower in the vitamin D insufficient group compared to the sufficient group (P=0.018 and P=0.028, respectively). The results for the ANOVAs indicated that velocities and counting rates were not significantly different by vitamin D status (Wilk’s Lambda =0.999; F (1, 95) =.11, P=.740) (Wilk’s Lambda =.999, F(1,95)=.13, P=.718). Vitamin D status was not significantly associated with dual task physical performance (defined as the difference in dual and single task) in gait velocity (OR=1.00, 95% CI: 0.98; 1.02, P=0.772) and counting rate (OR=1.684, 95% CI: 0.15; 19.57, P=0.677), when controlling for confounders. Conclusions: Since counting backward is a mental tracking task, which is a component of executive function, our results suggest a relationship between vitamin D insufficiency and executive dysfunction. Executive dysfunction has been previously associated with fall risks in the elderly, and it could be a possible mediator between vitamin D and falls. Our data suggest that cognition may play a significant role in vitamin D’s influence on falls, while motor function may play a lesser role.

CITATION:
J. Lopez ; A. Campa ; J.E. Lewis ; F.G. Huffman ; J.P. Liuzzi ; T. Li ; A.H. Martinez ; S.M. Ferris ; A. Rasul ; A. Farooqi ; A.M. Lopez Medrano ; S.E. Atlas ; E. Tiozzo ; J. Konefal ; J.M. Woolger (2016): Assessing the Relationship between Vitamin D Status and Impairments in Cognitive and Physical Performance in Older Adults Using a Dual Task Physical Performance Test . The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2016.114

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MODEST OVERWEIGHT AND HEALTHY DIETARY HABITS REDUCE RISK OF DEMENTIA: A NATIONWIDE SURVEY IN TAIWAN

C.-Y. Lee, Y. Sun, H.-J. Lee, T.-F. Chen, P.-N. Wang, K.-N. Lin, L.-Y. Tang, C.-C.Lin, M.-J. Chiu

J Prev Alz Dis 2017;1:37-43

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Background: Evidence of the associations of dietary habits and body mass index with dementia is inconsistent and limited in East Asian countries. Objective: We aim to explore the associations of dietary habits and body mass index with the odds of dementia. Design: Cross-sectional observational study. Setting: A nationwide, population-based, door-to-door, in-person survey. Participants: Selected by computerized random sampling from all 19 counties in Taiwan. Measurement: Diagnosis of dementia using the criteria recommended by the National Institute on Aging-Alzheimer’s Association. Lifestyle factors, dietary habits and demographic data were compared between normal subjects and participants with dementia. Results: A total of 10432 residents were assessed, among whom 2049 were classified as having a mild cognitive impairment (MCI), 929 were diagnosed with dementia, and 7035 were without dementia or MCI. After adjustment for age, gender, education, body mass index (BMI), dietary habits, habitual exercises and co-morbidities, including hypertension, diabetes and cerebrovascular diseases, we found inverse associations of dementia with the consumption of fish (OR 0.62, 95% CI 0.41-0.94), vegetables (OR 0.35, 95% CI 0.13-0.95), coffee (OR 0.59, 95% CI 0.35-0.97), green tea (OR 0.51, 95% CI 0.34-0.75) and other types of tea (OR 0.41, 95% CI 0.28-0.60). There was no association between dementia and fruit consumption. Compared with people who had a normal BMI (18 < BMI <= 24), older overweight people (24 < BMI <=30) had a reduced risk of dementia with an adjusted OR of 0.77 (95% CI 0.61-0.96). Conclusions: Our study provides preliminary evidence that suggests that the consumption of fish, vegetables, tea, and coffee has potential benefits against dementia in East Asian population. Being modestly overweight (nadir risk at BMI = 25) in late life was associated with decreased odds of dementia. The benefit of fruits may be offset by their high sugar content.

CITATION:
C.-Y. Lee ; Y. Sun ; H.-J. Lee ; T.-F. Chen ; P.-N. Wang ; K.-N. Lin ; L.-Y. Tang ; C.-C.Lin ; M.-J. Chiu (2016): Modest Overweight and Healthy Dietary Habits Reduce Risk of Dementia: A Nationwide Survey in Taiwan. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2016.123

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COGNITIVE PERFORMANCE DOES NOT LIMIT PHYSICAL ACTIVITY PARTICIPATION IN THE LIFESTYLE INTERVENTIONS AND INDEPENDENCE FOR ELDERS PILOT STUDY (LIFE-P)

K.F. Reid, M.P. Walkup, J.A. Katula, K.M. Sink, S. Anton, R. Axtell, D.R. Kerwin, A.C. King, A.F. Kramer, M.E. Miller, V. Myers, C. Rosano, S.A. Studenski, O.L. Lopez, J. Verghese, R.A. Fielding, J. Williamson

J Prev Alz Dis 2017;1:44-50

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Objectives: We examined whether multiple domains of baseline cognitive performance were associated with prospective physical activity (PA) adherence in the Lifestyle Interventions and Independence for Elders Pilot study (LIFE-P). Design, Setting, Participants: The LIFE-P study was a single-blind, multicenter, randomized controlled trial of a PA intervention compared to a successful aging educational intervention in sedentary, mobility-limited older adults. Intervention: A 12-month structured, moderate-intensity, multi-modal PA program that included walking, resistance training, and flexibility exercises. For the first 2 months (adoption), 3 center-based exercise sessions (40–60 min) / week were conducted. During the next 4 months (transition), center-based sessions were conducted 2 times / week. The subsequent maintenance phase consisted of optional once-to-twice-per-week center-based sessions and home-based PA. Measurements: Tests of executive and global cognitive functioning, working memory and psychomotor speed were administered at baseline. Median test scores were used to dichotomize participants into low or high cognitive performance groups. Results: 52 mobility-limited older adults (age: 76.9 ±5 yrs) were randomized to the PA arm of LIFE-P. Compared to participants with high cognitive performance, participants with low performance had similar PA adherence rates (all P ≥ 0.34). Furthermore, weak and non-significant univariate relationships were elicited between all measures of cognition and overall PA adherence levels (r values ranged: -0.20 to 0.12, P ≥ 0.12). Conclusion: These data suggest that cognitive performance does not limit long-term PA adherence in mobility-limited older adults. Additional studies in larger cohorts are warranted to verify these findings.

CITATION:
K.F. Reid ; M.P. Walkup ; J.A. Katula ; K.M. Sink ; S. Anton ; R. Axtell ; D.R. Kerwin ; A.C. King ; A.F. Kramer ; M.E. Miller ; V. Myers ; C. Rosano ; S.A. Studenski ; O.L. Lopez ; J. Verghese ; R.A. Fielding ; J. Williamson (2016): Cognitive Performance Does not Limit Physical Activity Participation in the Lifestyle Interventions and Independence for Elders Pilot Study (LIFE-P). The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2016.107

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Review Articles

A KETO-MEDIET APPROACH WITH COCONUT SUBSTITUTION AND EXERCISE MAY DELAY THE ONSET OF ALZHEIMER’S DISEASE AMONG MIDDLE-AGED

B.C. Perng, M. Chen, J.C. Perng, P. Jambazian

J Prev Alz Dis 2017;1:51-57

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Background: Coconut oil has been widely used to improve health because there is much information available by word of mouth, in books, and on the internet. However, researchers still continue to search for the best diets to improve the quality of life, especially for people with cognitive decline. Objectives: The aim of this review is to develop a novel dietary approach, the Keto-Mediet, which may help prevent the onset of Alzheimer’s disease. Methods: Evidence gained through literature review from 1982 to 2015 on gene-by-diet interaction and lipid and glucose metabolism in the brains of Alzheimer’s patients is converted into the new Keto-Mediet approach. Design: The Keto-Mediet approach combines the benefits of a Ketogenic diet and a Mediterranean diet into a pyramidal model that is rich in various types of vitamins and substitutes coconuts for saturated animal fats. Limited glucose intake is intended to delay brain degeneration. A revised adult food pyramid was created to illustrate the principles of the Keto-Mediet approach. Conclusion: The Keto-Mediet approach represents and interprets food groups according to the revised adult food pyramid. This approach also encourages adherence to this healthy diet and lifestyle changes including exercise for people whose age ranges from 40 to 75 years. Those who comply with this approach will significantly enhance their knowledge and adopt a healthier lifestyle, as compared to those whose modern eating patterns are typically less healthy. Therefore, the Keto-Mediet approach can be applied in hopes of preventing and decreasing Alzheimer’s disease in different ethnicities and cultural groups.

CITATION:
B.C. Perng ; M. Chen ; J.C. Perng ; P. Jambazian (2016): A Keto-Mediet Approach with Coconut Substitution and Exercise May Delay the Onset of Alzheimer’s Disease among Middle-Aged. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2016.104

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ANTIOXIDANTS IN THE DIET AND COGNITIVE FUNCTION: WHICH ROLE FOR THE MEDITERRANEAN LIFE-STYLE?

C. Vassalle, L. Sabatino, A. Pingitore, K. Chatzianagnostou, F. Mastorci, R. Ceravolo

J Prev Alz Dis 2017;1:58-64

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This review aims to focus on main antioxidants- abundantly contained in the diet- as well as of the whole Mediterranean diet and life-style and their relationship with cognitive function, especially critical in two phases of life, in children until adolescence and oldness. The role of emerging biochemical and molecular biomarkers as opportunity to estimate more accurately nutritional assumption and requirement, in terms of cognitive preservation and disease risk, will be also discussed. The cluster of factors within the Mediterranean pattern -which include not only nutritional, but also physical, social, and stimulating aspects- is still largely understudied as a whole, but it is proposed as attractive research area and tool for public health planning of prevention and intervention.

CITATION:
C. Vassalle ; L. Sabatino ; A. Pingitore ; K. Chatzianagnostou ; F. Mastorci ; R. Ceravolo (2016): Antioxidants in the Diet and Cognitive Function: Which Role for the Mediterranean Life-style?. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2016.109

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