04/2015 journal articles
Editorials
LESSONS TO BE LEARNED ABOUT CLINICAL TRIALS IN PRECLINICAL AD FROM ONGOING LONGITUDINAL STUDIES
M.S. Albert
J Prev Alz Dis 2015;2(4):214-215
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CITATION:
M.S. Albert (2015): Lessons to Be Learned about Clinical Trials in Preclinical AD from Ongoing Longitudinal Studies. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2015.83
DRUG DEVELOPMENT IN AD: POINT OF VIEW FROM THE INDUSTRY
E. Siemers
J Prev Alz Dis 2015;2(4):216-218
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CITATION:
E. Siemers (2015): Drug Development in AD: Point of View from the Industry. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2015.80
Original Research
IMPACT OF DIETARY FACTORS AND INFLAMMATION ON COGNITION AMONG OLDER ADULTS
E.P. Handing, B.J. Small, S.L. Reynolds, N.B. Kumar
J Prev Alz Dis 2015;2(4):220-226
Show summaryHide summaryOBJECTIVE: This study examined the influence of age, nutrition (as measured through food diaries and serum/plasma biomarkers) and inflammatory markers on cognitive performance in adults 60 years of age and older.
DESIGN: A cross-sectional population based study, data from the National Health and Nutrition Examination Survey (NHANES; 2001-2002 wave).
PARTICIPANTS: This study included 1,048 adults who had valid dietary data, blood biomarkers, were 60 years or older, completed the cognitive test, and had complete demographic information.
METHOD: A series of regression models were used to examine the relationship between cognitive function as measured by the Digit Symbol Substitution Task (DSST), dietary factors/biomarkers and inflammation. Mediation analyses were then utilized to examine whether individual nutrients accounted for the relationships between age and DSST performance.
RESULTS: Dietary fat intake, serum vitamin E, serum folate, serum iron, plasma homocysteine, and serum vitamin D were significantly associated with better DSST performance. Elevated fibrinogen and C-reactive protein, were significantly associated with poorer cognitive function, but did not remain statistically significant after controlling for age, gender, education, ethnicity, income, and total calorie intake. Serum vitamin D and plasma homocysteine accounted for a portion of age-related variance in DSST. Specifically, higher levels of vitamin D were related to better DSST performance, while higher homocysteine resulted in poorer cognitive performance.
CONCLUSION: Diet and nutrition are important modifiable factors that can influence health outcomes and may be beneficial to remediate age-related declines in cognition. Adequate nutrition may provide a primary preventive approach to healthy aging and maintenance of cognitive functioning in older adults.
CITATION:
E.P. Handing ; B.J. Small ; S.L. Reynolds ; N.B. Kumar (2015): Impact of Dietary Factors and Inflammation on Cognition among Older Adults. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2015.50
A COMBINED MEASURE OF COGNITION AND FUNCTION FOR CLINICAL TRIALS: THE INTEGRATED ALZHEIMER’S DISEASE RATING SCALE (IADRS)
A.M. Wessels, E.R. Siemers, P. Yu, S.W. Andersen, K.C. Holdridge, J.R. Sims, K. Sundell, Y. Stern, D.M. Rentz, B. Dubois, R.W. Jones, J. Cummings, P.S. Aisen
J Prev Alz Dis 2015;2(4):227-241
Show summaryHide summaryIt is generally recognized that more sensitive instruments for the earliest stages of Alzheimer’s disease (AD) are needed. The integrated Alzheimer’s Disease Rating Scale (iADRS) combines scores from 2 widely accepted measures, the Alzheimer’s Disease Assessment Scale-Cognitive subscale (ADAS-Cog) and the Alzheimer’s Disease Cooperative Study – instrumental Activities of Daily Living (ADCS-iADL). Disease progression and treatment differences as measured by the iADRS were analyzed using data from solanezumab EXPEDITION, EXPEDITION2, and EXPEDITION-EXT Studies; semagacestat IDENTITY Study; and donepezil ADCS – mild cognitive impairment (ADCS-MCI) Study. Psychometric properties of the iADRS were established through principal component analysis (PCA) and estimation of contributions of subscores and individual item scores to the iADRS total score. The iADRS performed better than most composites and scales in detecting disease progression and comparably or better than individual scales in detecting treatment differences. PCA demonstrated the iADRS can be divided into two principal components primarily representing cognitive items and instrumental ADLs. Dynamic ranges of the subscales were similar across all studies, reflecting approximately equal contributions from both subscales to the iADRS total score. In item analyses, every item contributed to the total score, with varying strength of contributions by item and across data sets. The iADRS demonstrated acceptable psychometric properties and was effective in capturing disease progression from MCI through moderate AD and treatment effects across the early disease spectrum. These findings suggest the iADRS can be used in studies of mixed populations, ensuring sensitivity to treatment effects as subjects progress during studies of putative disease-modifying agents.
CITATION:
A.M. Wessels ; E.R. Siemers ; P. Yu ; S.W. Andersen ; K.C. Holdridge ; J.R. Sims ; K. Sundell ; Y. Stern ; D.M. Rentz ; B. Dubois ; R.W. Jones ; J. Cummings ; P.S. Aisen (2015): A Combined Measure of Cognition and Function for Clinical Trials: The Integrated Alzheimer’s Disease Rating Scale (iADRS) . The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2015.82
THE HARVARD AUTOMATED PHONE TASK: NEW PERFORMANCE-BASED ACTIVITIES OF DAILY LIVING TESTS FOR EARLY ALZHEIMER’S DISEASE
G.A. Marshall, M. Dekhtyar, J.M. Bruno, K. Jethwani, R.E. Amariglio, K.A. Johnson, R.A. Sperling, D.M. Rentz
J Prev Alz Dis 2015;2(4):242-253
Show summaryHide summaryBackground: Impairment in activities of daily living is a major burden for Alzheimer’s disease dementia patients and caregivers. Multiple subjective scales and a few performance-based instruments have been validated and proven to be reliable in measuring instrumental activities of daily living in Alzheimer’s disease dementia but less so in amnestic mild cognitive impairment and preclinical Alzheimer’s disease.
Objective: To validate the Harvard Automated Phone Task, a new performance-based activities of daily living test for early Alzheimer’s disease, which assesses high level tasks that challenge seniors in daily life.
Design: In a cross-sectional study, the Harvard Automated Phone Task was associated with demographics and cognitive measures through univariate and multivariate analyses; ability to discriminate across diagnostic groups was assessed; test-retest reliability with the same and alternate versions was assessed in a subset of participants; and the relationship with regional cortical thickness was assessed in a subset of participants.
Setting: Academic clinical research center.
Participants: One hundred and eighty two participants were recruited from the community (127 clinically normal elderly and 45 young normal participants) and memory disorders clinics at Brigham and Women’s Hospital and Massachusetts General Hospital (10 participants with mild cognitive impairment).
Measurements: As part of the Harvard Automated Phone Task, participants navigated an interactive voice response system to refill a prescription (APT-Script), select a new primary care physician (APT-PCP), and make a bank account transfer and payment (APT-Bank). The 3 tasks were scored based on time, errors, and repetitions from which composite z-scores were derived, as well as a separate report of correct completion of the task.
Results: We found that the Harvard Automated Phone Task discriminated well between diagnostic groups (APT-Script: p=0.002; APT-PCP: p<0.001; APT-Bank: p=0.02), had an incremental level of difficulty, and had excellent test-retest reliability (Cronbach’s α values of 0.81 to 0.87). Within the clinically normal elderly, there were significant associations in multivariate models between performance on the Harvard Automated Phone Task and executive function (APT-PCP: p<0.001), processing speed (APT-Script: p=0.005), and regional cortical atrophy (APT-PCP: p=0.001; no significant association with APT-Script) independent of hearing acuity, motor speed, age, race, education, and premorbid intelligence.
Conclusions: Our initial experience with the Harvard Automated Phone Task, which consists of ecologically valid, easily-administered measures of daily activities, suggests that these tasks could be useful for screening and tracking the earliest functional alterations in preclinical and early prodromal AD.
CITATION:
G.A. Marshall ; M. Dekhtyar ; J.M. Bruno ; K. Jethwani ; R.E. Amariglio ; K.A. Johnson ; R.A. Sperling ; D.M. Rentz (2015): The Harvard Automated Phone Task: New Performance-Based Activities of Daily Living Tests for Early Alzheimer’s Disease. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2015.72
Review Articles
THE ALZHEIMER’S PREVENTION CLINIC AT WEILL CORNELL MEDICAL COLLEGE / NEW YORK - PRESBYTERIAN HOSPITAL: RISK STRATIFICATION AND PERSONALIZED EARLY INTERVENTION
A. Seifan, R. Isaacson
J Prev Alz Dis 2015;2(4):254-266
Show summaryHide summaryIn July 2013, Weill Cornell Medical College founded the first Alzheimer’s Prevention Clinic (APC) in the United States, providing direct clinical care to family members of patients with Alzheimer’s disease (AD) as part of the Weill Cornell Memory Disorders Program. At the APC, patients seeking to lower their AD risk undergo a comprehensive assessment, receive a personalized plan based on rapidly evolving scientific evidence, and are followed over time using validated as well as emerging clinical and research technologies. The APC approach applies the principles of pharmacogenomics, nutrigenomics and clinical precision medicine, to tailor individualized therapies for patients. Longitudinal measures currently assessed in the clinic include anthropometrics, cognition, blood biomarkers (i.e., lipid, inflammatory, metabolic, nutritional) and genetics, as well as validated, self-reported measures that enable patients to track several aspects of health-related quality of life. Patients are educated on the fundamental concepts of AD prevention via an interactive online course hosted on Alzheimer’s Universe (www.AlzU.org), which also contains several activities including validated computer-based cognitive testing. The primary goal of the APC is to employ preventative measures that lower modifiable AD risk, possibly leading to a delay in onset of future symptoms. Our secondary goal is to establish a cohort of at-risk individuals who will be primed to participate in future AD prevention trials as disease-modifying agents emerge for testing at earlier stages of the AD process. The clinical services are intended to lower concern for future disease by giving patients a greater sense of control over their brain health.
CITATION:
A. Seifan ; R. Isaacson (2015): The Alzheimer’s Prevention Clinic at Weill Cornell Medical College / New York - Presbyterian Hospital: Risk Stratification and Personalized Early Intervention. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2015.81
Clinical Trials and Aging: 8th Conference Clinical Trials on Alzheimer’s Disease, November 5-7, 2015, Barcelona, Spain
CTAD: SYMPOSIA, ORAL COMMUNICATIONS, POSTERS
Abstracts
J Prev Alz Dis 2015;2(4):269-396
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