02/2022 journal articles
WHERE DO WE GO FROM HERE?
J Prev Alz Dis 2022;2(9):188-189Show summaryHide summary
R.C. Petersen (2022): Where Do We Go from Here?. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2022.35
THE ‘ADUCANUMAB STORY’: WILL THE LAST CHAPTER SPELL THE END OF THE ‘AMYLOID HYPOTHESIS’ OR MARK A NEW BEGINNING?
J Prev Alz Dis 2022;2(9):190-192Show summaryHide summary
Z.S. Khachaturian ; (2022): The ‘Aducanumab Story’: Will the Last Chapter Spell the End of the ‘Amyloid Hypothesis’ or Mark a New Beginning?. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2022.36
ADUCANUMAB TRIALS EMERGE BUT DON’T ENGAGE
J Prev Alz Dis 2022;2(9):193-196Show summaryHide summary
L.S. Schneider ; (2022): Aducanumab Trials EMERGE But Don’t ENGAGE. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2022.37
TWO RANDOMIZED PHASE 3 STUDIES OF ADUCANUMAB IN EARLY ALZHEIMER’S DISEASE
S. Budd Haeberlein, P.S. Aisen, F. Barkhof, S. Chalkias, T. Chen, S. Cohen, G. Dent, O. Hansson, K. Harrison, C. von Hehn, T. Iwatsubo, C. Mallinckrodt, C.J. Mummery, K.K. Muralidharan, I. Nestorov, L. Nisenbaum, R. Rajagovindan, L. Skordos, Y. Tian, C.H. van Dyck, B. Vellas, S. Wu, Y. Zhu, A. Sandrock
J Prev Alz Dis 2022;2(9):197-210Show summaryHide summary
BACKGROUND: Alzheimer’s disease is a progressive, irreversible, and fatal disease for which accumulation of amyloid beta is thought to play a key role in pathogenesis. Aducanumab is a human monoclonal antibody directed against aggregated soluble and insoluble forms of amyloid beta.
OBJECTIVES: We evaluated the efficacy and safety of aducanumab in early Alzheimer’s disease.
DESIGN: EMERGE and ENGAGE were two randomized, double-blind, placebo-controlled, global, phase 3 studies of aducanumab in patients with early Alzheimer’s disease.
SETTING: These studies involved 348 sites in 20 countries.
PARTICIPANTS: Participants included 1638 (EMERGE) and 1647 (ENGAGE) patients (aged 50–85 years, confirmed amyloid pathology) who met clinical criteria for mild cognitive impairment due to Alzheimer's disease or mild Alzheimer's disease dementia, of which 1812 (55.2%) completed the study.
INTERVENTION: Participants were randomly assigned 1:1:1 to receive aducanumab low dose (3 or 6 mg/kg target dose), high dose (10 mg/kg target dose), or placebo via IV infusion once every 4 weeks over 76 weeks.
MEASUREMENTS: The primary outcome measure was change from baseline to week 78 on the Clinical Dementia Rating Sum of Boxes (CDR-SB), an integrated scale that assesses both function and cognition. Other measures included safety assessments; secondary and tertiary clinical outcomes that assessed cognition, function, and behavior; and biomarker endpoints.
RESULTS: EMERGE and ENGAGE were halted based on futility analysis of data pooled from the first approximately 50% of enrolled patients; subsequent efficacy analyses included data from a larger data set collected up to futility declaration and followed prespecified statistical analyses. The primary endpoint was met in EMERGE (difference of −0.39 for high-dose aducanumab vs placebo [95% CI, −0.69 to −0.09; P=.012; 22% decrease]) but not in ENGAGE (difference of 0.03, [95% CI, −0.26 to 0.33; P=.833; 2% increase]). Results of biomarker substudies confirmed target engagement and dose-dependent reduction in markers of Alzheimer's disease pathophysiology. The most common adverse event was amyloid-related imaging abnormalities-edema.
CONCLUSIONS: Data from EMERGE demonstrated a statistically significant change across all four primary and secondary clinical endpoints. ENGAGE did not meet its primary or secondary endpoints. A dose- and time-dependent reduction in pathophysiological markers of Alzheimer’s disease was observed in both trials.
S. Budd Haeberlein ; P.S. Aisen ; F. Barkhof ; S. Chalkias ; T. Chen ; S. Cohen ; G. Dent ; O. Hansson ; K. Harrison ; C. von Hehn ; T. Iwatsubo ; C. Mallinckrodt ; C.J. Mummery ; K.K. Muralidharan ; I. Nestorov ; L. Nisenbaum ; R. Rajagovindan ; L. Skordos ; Y. Tian ; C.H. van Dyck ; B. Vellas ; S. Wu ; Y. Zhu ; A. Sandrock (2022): Two Randomized Phase 3 Studies of Aducanumab in Early Alzheimer’s Disease. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2022.30
DETECTION AND MANAGEMENT OF AMYLOID-RELATED IMAGING ABNORMALITIES IN PATIENTS WITH ALZHEIMER’S DISEASE TREATED WITH ANTI-AMYLOID BETA THERAPY
J. Barakos, D. Purcell, J. Suhy, S. Chalkias, P. Burkett, C. Marsica Grassi, C. Castrillo-Viguera, I. Rubino, E. Vijverberg
J Prev Alz Dis 2022;2(9):211-220Show summaryHide summary
Amyloid-related imaging abnormalities (ARIA) are adverse events reported in Alzheimer’s disease trials of anti-amyloid beta (Aβ) therapies. This review summarizes the existing literature on ARIA, including bapineuzumab, gantenerumab, donanemab, lecanemab, and aducanumab studies, with regard to potential risk factors, detection, and management. The pathophysiology of ARIA is unclear, but it may be related to binding of antibodies to accumulated Aβ in both the cerebral parenchyma and vasculature, resulting in loss of vessel wall integrity and increased leakage into surrounding tissues. Radiographically, ARIA-E is identified as vasogenic edema in the brain parenchyma or sulcal effusions in the leptomeninges/sulci, while ARIA-H is hemosiderin deposits presenting as microhemorrhages or superficial siderosis. ARIA tends to be transient and asymptomatic in most cases, typically occurring early in the course of treatment, with the risk decreasing later in treatment. Limited data are available on continued dosing following radiographic findings of ARIA; hence, in the event of ARIA, treatment should be continued with caution and regular monitoring. Clinical trials have implemented management approaches such as temporary suspension of treatment until symptoms or radiographic signs of ARIA have resolved or permanent discontinuation of treatment. ARIA largely resolves without concomitant treatment, and there are no systematic data on potential treatments for ARIA. Given the availability of an anti-Aβ therapy, ARIA monitoring will now be implemented in routine clinical practice. The simple magnetic resonance imaging sequences used in clinical trials are likely sufficient for effective detection of cases. Increased awareness and education of ARIA among clinicians and radiologists is vital.
J. Barakos ; D. Purcell ; J. Suhy ; S. Chalkias ; P. Burkett ; C. Marsica Grassi ; C. Castrillo-Viguera ; I. Rubino ; E. Vijverberg ; (2022): Detection and Management of Amyloid-Related Imaging Abnormalities in Patients with Alzheimer’s Disease Treated with Anti-Amyloid Beta Therapy. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2022.21
ADUCANUMAB: APPROPRIATE USE RECOMMENDATIONS UPDATE
J. Cummings, G.D. Rabinovici, A. Atri, P. Aisen, L.G. Apostolova, S. Hendrix, M. Sabbagh, D. Selkoe, M. Weiner, S. Salloway
J Prev Alz Dis 2022;2(9):221-230Show summaryHide summary
Aducanumab (Aduhelm) is approved in the United States for the treatment of patients with mild cognitive impairment due to Alzheimer's disease or mild AD dementia. Aducanumab Appropriate Use Recommendations (AURs) have been published and have helped guide best practices for use of aducanumab. As real-world use has occurred and more information has accrued, the AURs require refinement. We update the AURs to better inform appropriate patient selection and improve shared decision-making, safety monitoring, and risk mitigation in treated patients. Based on evolving experience we emphasize the importance of detecting past medical conditions that may predispose to amyloid related imaging abnormalities (ARIA) or may increase the likelihood of ARIA complications including autoimmune or inflammatory conditions, seizures, or disorders associated with extensive white matter pathology. The apolipoprotein E ε4 (APOE4) genotype is strongly associated with ARIA and exhibits a gene dose effect. We recommend that clinicians perform APOE genotyping to better inform patient care decisions, discussions regarding risk, and clinician vigilance concerning ARIA. As most ARIA occurs during the titration period of aducanumab, we suggest performing MRI before the 5th, 7th, 9th, and 12th infusions to improve detection. Uncommonly, ARIA may be recurrent or serious; we suggest additional parameters for treatment discontinuation taking these observations into account. It is important to continue to learn from the real-world use of aducanumab and the AURs will continue to evolve as new information becomes available. This AUR update does not address efficacy, price, or insurance coverage and is provided to assist clinicians to establish best practices for use of aducanumab in the treatment of patients with mild cognitive impairment and mild Alzheimer’s dementia.
J. Cummings ; G.D. Rabinovici ; A. Atri ; P. Aisen ; L.G. Apostolova ; S. Hendrix ; M. Sabbagh ; D. Selkoe ; M. Weiner ; S. Salloway (2022): Aducanumab: Appropriate Use Recommendations Update. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2022.34
THERAPEUTIC TARGETS FOR ALZHEIMER’S DISEASE: AMYLOID VS. NON-AMYLOID. WHERE DOES CONSENSUS LIE TODAY? AN CTAD TASK FORCE REPORT
S. Gauthier, A. Boxer, D. Knopman, J. Sims, R. Doody, P. Aisen, T. Iwatsubo, R. Bateman, B. Vellas
J Prev Alz Dis 2022;2(9):231-235Show summaryHide summary
There was consensus that both amyloid and tau pathologies should be targeted in Alzheimer’s disease, as well as additional pathophysiological mechanisms such as neuroinflammation. The selection of one or both of these targets may depend upon a personalized approach that takes into account the genetic and acquired factors that cause AD in any given person as well as their stage of disease as reflected in a biomarker profile. The validation of this therapeutic approach will be made possible by new methodologies for subdividing into predominant pathology, by efficient methods for identifying people in the earliest stages of disease, and by combination studies.
S. Gauthier ; A. Boxer ; D. Knopman ; J. Sims ; R. Doody ; P. Aisen ; T. Iwatsubo ; R. Bateman ; B. Vellas ; (2022): Therapeutic Targets for Alzheimer’s Disease: Amyloid Vs. Non-Amyloid. Where Does Consensus Lie Today? An CTAD Task Force Report. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2022.29
DIGITAL THERAPEUTICS FOR MCI AND ALZHEIMER’S DISEASE: A REGULATORY PERSPECTIVE - HIGHLIGHTS FROM THE CLINICAL TRIALS ON ALZHEIMER’S DISEASE CONFERENCE (CTAD)
J. Shuren, P.M. Doraiswamy
J Prev Alz Dis 2022;2(9):236-240Show summaryHide summary
J. Shuren ; P.M. Doraiswamy ; (2022): Digital Therapeutics for MCI and Alzheimer’s disease: A Regulatory Perspective - Highlights From The Clinical Trials on Alzheimer’s Disease conference (CTAD). The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2022.28
PUBLIC POLICY SHOULD FOSTER ALZHEIMER’S TREATMENT AVAILABILITY: COMMENT ON THE DRAFT US MEDICARE DECISION TO LIMIT PAYMENT FOR ADUCANUMAB (ADUHELMTM) TO PATIENTS PARTICIPATING IN CLINICAL TRIALS
J Prev Alz Dis 2022;2(9):241-246Show summaryHide summary
J. Cummings (2022): Public Policy Should Foster Alzheimer’s Treatment Availability: Comment on the Draft US Medicare Decision to Limit Payment for Aducanumab (AduhelmTM) to Patients Participating in Clinical Trials. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2022.25
A POLYMORPHISM CLUSTER AT THE 2Q12 LOCUS MAY PREDICT RESPONSE TO PIROMELATINE IN PATIENTS WITH MILD ALZHEIMER\'S DISEASE
L.S. Schneider, M. Laudon, T. Nir, J. Caceres, G. Ianniciello, M. Capulli, N. Zisapel
J Prev Alz Dis 2022;2(9):255-261Show summaryHide summary
Background: Piromelatine is a novel melatonin MT1/2/3 and serotonin 5-HT-1A/1D receptors agonist developed for mild Alzheimer’s disease (AD). In a randomized, placebo-controlled, dose-ranging study (ReCognition) of piromelatine (5, 20, and 50 mg daily for 6 months) in participants with mild dementia due to AD (n=371, age 60-85 years), no statistically significant differences were found between the piromelatine and placebo-treated groups on the primary (i.e., computerized neuropsychological test battery (cNTB)) and secondary outcomes (ADCS-CGIC, ADCS-MCI-ADL, ADAS-cog14, NPI, and Pittsburgh Sleep Quality Index (PSQI)) nor were there safety concerns (https://clinicaltrials.gov/ct2/show/NCT02615002).
Objectives: This study was aimed at identifying genetic markers predicting piromelatine treatment response using a genome-wide association approach (GWAS).
Design: Variant genotyping of a combined whole genome and whole exome sequencing was performed using DNA extracted from lymphocytes from consenting participants. The general case-control allelic test was performed on piromelatine-treated participants, taking “responders” (i.e., >0.125 change from baseline in the cNTB) as cases and “non responders” as controls, using a Cochran-Armitage trend test.
Setting: 58 outpatient clinics in the US.
Participants: 371 participants were randomized in the trial; 107 provided informed consent for genotyping.
Results: The GWAS sample did not differ from the full study cohort in demographics, baseline characteristics, or response to piromelatine. Six single-nucleotide polymorphisms (SNPs) in chromosome 2q12 (2:107,510,000-107,540,000) were associated with response (p-value < 1x10 -4 each). Post hoc analyses suggested that the carriers of the 2q12 polymorphism cluster (27% of the GWAS sample) improved significantly on the cNTB on piromelatine as compared to placebo but significantly worsened on the ADAS-Cog14 and PSQI. By contrast, “non-carriers” improved significantly with piromelatine compared to placebo on the ADAS-Cog14 ( 2.91 (N=23) with piromelatine 20 mg vs 1.65 (N=19) with placebo (p=0.03)) and PSQI.
Conclusions: The 2q12 (2:107,510,000-107,540,000) 5-6 SNPs cluster may predict efficacy of piromelatine for mild AD. These findings warrant further investigation in a larger, prospective early-stage AD clinical trial for patients who are non-carriers of the 2q12 polymorphism cluster.
L.S. Schneider ; M. Laudon ; T. Nir ; J. Caceres ; G. Ianniciello ; M. Capulli ; N. Zisapel ; (2021): A Polymorphism Cluster at the 2q12 locus May Predict Response to Piromelatine in Patients with Mild Alzheimer's Disease. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2021.61
SENSITIVITY OF THE PRECLINICAL ALZHEIMER’S COGNITIVE COMPOSITE (PACC), PACC5, AND REPEATABLE BATTERY FOR NEUROPSYCHOLOGICAL STATUS (RBANS) TO AMYLOID STATUS IN PRECLINICAL ALZHEIMER’S DISEASE -ATABECESTAT PHASE 2B/3 EARLY CLINICAL TRIAL
K.V. Papp, H. Rofael, A.E. Veroff, M.C. Donohue, S. Wang, C. Randolph, E. Grober, H.R. Brashear, G. Novak, K. Ernstrom, R. Raman, P.S. Aisen, R. Sperling, G. Romano, D. Henley
J Prev Alz Dis 2022;2(9):255-261Show summaryHide summary
Background: Cognitive composites commonly serve as primary outcomes in Alzheimer’s disease (AD) secondary prevention trials.
Objective: To evaluate the association between amyloid (Aβ) burden level (+/-) and performance on three separate composite endpoints: Preclinical Alzheimer’s Cognitive Composite (PACC), PACC+Semantic Fluency (PACC5), and Repeatable Battery for Neuropsychological Status (RBANS).
Design: Screening data from the randomized, double-blind, placebo-controlled, phase 2b/3 atabecestat EARLY study in preclinical AD participants were used in this analysis.
Setting: The EARLY study was conducted at 143 centers across 14 countries.
Participants: 3,569 cognitively unimpaired older adults (Clinical Dementia Rating of 0; aged 60-85 years) screened for inclusion in the EARLY study with Aβ status and at least PACC or RBANS at screening were included. Participants were categorized as those with non-pathological Aβ levels (Aβ-, n=2,824) and those with pathological Aβ levels (Aβ+, n=745) based on florbetapir uptake or levels of cerebrospinal fluid
Measurements: Analysis of Covariance models controlling for age, sex, and education were used to examine the difference in PACC, PACC5, and RBANS between Aβ groups. Nonparametric bootstrap was used to compare sensitivity of composites to differentiate between Aβ status.
Results: Of 3,569 participants, 2,116 were women (59%); 3,006 were Caucasian (84%); mean (SD) age was 68.98 (5.28) years. Aβ+ participants performed worse versus Aβ- participants on all cognitive composites though the magnitude of the Aβ effect was generally small. The Aβ+/- effect size for the PACC (Cohen’s d=-0.15) was significantly greater than the RBANS (d=-0.097) while the PACC5 effect size (d=-0.139) was numerically larger than the RBANS. When examining subscores from the composites, memory tests (i.e., Free and Cued Selective Reminding Test, Figure Recall) and speed of processing (i.e., Digit-Symbol/Coding on the PACC/RBANS) exhibited the largest Aβ+/- effect sizes.
Conclusions: Cross-sectional relationships between Aβ and cognition among clinically unimpaired older adults are detectable on multi-domain cognitive composites but are relatively small in magnitude. The Aβ+/- group effect was statistically larger for PACC and marginally larger for PACC5 versus RBANS. However, interpretation of composite sensitivity to Aβ status cross-sectionally cannot be generalized to sensitivity to change over time.
K.V. Papp ; H. Rofael ; A.E. Veroff ; M.C. Donohue ; S. Wang ; C. Randolph ; E. Grober ; H.R. Brashear ; G. Novak ; K. Ernstrom ; R. Raman ; P.S. Aisen ; R. Sperling ; G. Romano ; D. Henley ; (2022): Sensitivity of the Preclinical Alzheimer’s Cognitive Composite (PACC), PACC5, and Repeatable Battery for Neuropsychological Status (RBANS) to Amyloid Status in Preclinical Alzheimer’s Disease -Atabecestat Phase 2b/3 EARLY Clinical Trial. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2022.17
UNSUPERVISED PERFORMANCE OF THE COGSTATE BRIEF BATTERY IN THE BRAIN HEALTH REGISTRY: IMPLICATIONS FOR DETECTING COGNITIVE DECLINE
T. Banh, C. Jin, J. Neuhaus, R.S. Mackin, P. Maruff, N. Stricker, M.W. Weiner, R.L. Nosheny
J Prev Alz Dis 2022;2(9):262-268Show summaryHide summary
Introduction: The feasibility and validity of unsupervised, longitudinal brief computerized cognitive batteries is unknown.
Methods: Participants aged 56-90 (N = 19476) from the Brain Health Registry (BHR) completed the CogState Brief Battery (CBB) at 6-month intervals over a period of 5 years. We used linear mixed-effects models to assess whether cross-sectional and longitudinal performance on CBB within BHR was associated with demographic and cognitive characteristics. We also defined a group of CBB decliners based on subject-specific slopes and estimated associations between decliner status and participant characteristics.
Results: We found weak associations between longitudinal change in CBB and participant characteristics. Cross-sectional CBB scores were significantly associated with participant characteristics such as age, gender, ethnicity, self-reported disease status, and memory concern. CBB decliners were more likely to self-report mild cognitive impairment (MCI) and memory concerns.
Discussion: Cross-sectional, remote CBB shows evidence of construct validity, but our results suggest that longitudinal assessment may not provide additional value for identifying those at risk for and with cognitive impairment.
T. Banh ; C. Jin ; J. Neuhaus ; R.S. Mackin ; P. Maruff ; N. Stricker ; M.W. Weiner ; R.L. Nosheny (2021): Unsupervised Performance of the CogState Brief Battery in the Brain Health Registry: Implications for Detecting Cognitive Decline. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2021.68
VALIDITY OF ONLINE VERSUS IN-CLINIC SELF-REPORTED EVERYDAY COGNITION SCALE
T. Howell, J. Neuhaus, M.M. Glymour, M.W. Weiner, R.L Nosheny
J Prev Alz Dis 2022;2(9):269-276Show summaryHide summary
BACKGROUND: Online cognitive assessments are alternatives to in-clinic assessments.
Objectives: We evaluated the relationship between online and in-clinic self-reported Everyday Cognition Scale (ECog).
Methods: In 94 Alzheimer’s Disease Neuroimaging Initiative and Brain Health Registry (ADNI-BHR) participants, we estimated associations between online and in-clinic Everyday Cognition using Bland-Altman plots and regression. In 472 ADNI participants, we estimated reliability of in-clinic Everyday Cognition completed six months apart using Bland-Altman plots and regression.
Results: Online Everyday Cognition associations: Mean difference was 0.11 (95% limits of agreement: -0.41 to 0.64). In-clinic Everyday Cognition score increased by 0.81 for each online Everyday Cognition score unit increase (R2=0.60). In-clinic Everyday Cognition reliability: Mean difference was 0.01 (95% limits of agreement: -0.61 to 0.62). In-clinic Everyday Cognition score at enrollment increased by 0.79 for each in-clinic Everyday Cognition score unit increase at six months (R2=0.61).
Conclusion: Online Everyday Cognition closely corresponded with in-clinic Everyday Cognition, supporting validity of using online cognitive assessments to more efficiently facilitate Alzheimer’s disease research.
T. Howell ; J. Neuhaus ; M.M. Glymour ; M.W. Weiner ; R.L Nosheny (2022): Validity of Online Versus In-Clinic Self-Reported Everyday Cognition Scale. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2022.19
ALZHEIMER\'S DISEASE PREVENTION HEALTH COACHING
A. Rhodes, J. Inker, J. Richardson, F. Zanjani
J Prev Alz Dis 2022;2(9):277-285Show summaryHide summary
Background: Widespread lifestyle risk reduction at the community level is considered effective in decreasing Alzheimer's disease (AD). To address the limited use of risk deduction in AD, this study aimed to explore the feasibility of community-level implementation. Diverse older adults (60+) living in Richmond, VA, with incomes below $12,000/year and managing diabetic/cardiovascular symptoms were offered weekly lifestyle telephone-health coaching for 12-weeks in 2019-2020 (Phase 1). The health coaching sessions were framed to provide AD lifestyle risk reduction education, goal setting, and support: motivations and self-efficacy. The study sample (n=40, mean age 68 years (range: 60-76 years)) was 90% African American/Black (n=36), 100% Non-Hispanic, and 45% males (n=18). Twenty-five participants (60%) reported experiencing some/often memory problems in the last 12-months. Thirty-nine (95%) of subjects successfully participated in coaching sessions; on average, 11 (91.9%) sessions per subject were completed. Participants provided positive anecdotal feedback and stated the need for continued health coaching. Consequently, n=30 (75%) of the original sample consented to continued health coaching during the 2020-2021 COVID-19 pandemic (Phase 2). All study subjects were examined at baseline (Time 1), 3-month (Time 2), covid-baseline (Time 3), and 3-months postcovid-baseline (Time 4). Repeated Measures ANOVAs were done to examine Time and Time*Memory Status effects.
RESULTS: There was a total risk reduction at Phase 1 (F=9.26; p=.004; effect size=.19). At Phase 2, alcohol use decreased (p=.05), quadratic time effects were observed in physical activity (p=.01-.02), and cubic time effects were observed in depression (p=.02). Overall, total risk reduction in Phase 2 was observed at F=5.05; p=.03 effect size=.16. Pre/post-test analyses indicated improvement in Memory Problem Time Interaction (p=.007), AD knowledge (p=.01-.03), and Tired Days (p=.04) across Phase 1. There was also improvement in Social Isolation Time Interaction (p=.03); Tobacco Addiction (p=.001); Poor Mental Health Days (p=.05), and Worried Days Time Interaction (p=.02-.01) across Phase 2. Between subject Memory Status effects, indicating poorer baseline levels for individuals reporting memory problems had greater improvement seen in memory complaints (p=.001), poor mental health days (.02), and tired days (.003-.01).
CONCLUSIONS: This preliminary work creates the impetus for future large-scale lifestyle AD risk reduction investigations to mitigate and improve modifiable AD risk among low-income, diverse older adults, including individuals reporting memory problems. Our findings surrounding participant engagement and positive trends in AD risk reduction support the hypothesis that telephone-based health coaching is a practical and feasible AD risk reduction intervention.
A. Rhodes ; J. Inker ; J. Richardson ; F. Zanjani ; (2022): Alzheimer's Disease Prevention Health Coaching. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2022.33
ANXIETY AND DEPRESSIVE SYMPTOMS AND CORTICAL AMYLOID-Β BURDEN IN COGNITIVELY UNIMPAIRED OLDER ADULTS
C.K. Lewis, O.M. Bernstein, J.D. Grill, D.L. Gillen, D.L. Sultzer
J Prev Alz Dis 2022;2(9):286-296Show summaryHide summary
Background: There is evidence of relationships between behavioral symptoms and increased risk for Alzheimer’s Disease and/or Alzheimer’s Disease biomarkers. However, the nature of this relationship is currently unknown.
Objectives: To evaluate the relationship between anxiety and depressive symptoms and amyloid-β deposition in cognitively unimpaired older adults, and to assess mediating effects of either objective or subjective cognitive skills.
Design: Cross-sectional analysis of screening data from participants enrolled in the Anti-Amyloid Treatment in Asymptomatic Alzheimer Disease (A4) Study (ClinicalTrials.gov Identifier: NCT02008357)
Setting: Data analysis
Participants: 4492 cognitively unimpaired adults, age 65-85, enrolled in the Anti-Amyloid Treatment in Asymptomatic Alzheimer Disease (A4) Study
Measurements: We used linear regression to estimate the associations between amyloid-β standard uptake value ratio (SUVR) and Geriatric Depression Scale (GDS) and State Trait Anxiety Inventory (STAI) scores while adjusting for potential confounding factors as well as for Cognitive Function Index (CFI) or Preclinical Alzheimer’s Cognitive Composite (PACC) scores as possible mediational variables.
Results: 4399 subjects with complete covariates were included (mean age: 71.3, 59% female), GDS ranged 0-13 (mean: 1.0), and STAI ranged 6-24 (mean: 9.9). Amyloid-β SUVR was modestly associated with STAI; mean STAI score was estimated to be 0.275 points higher (95% CI: 0.038, 0.526; p-value = 0.023) for each 0.5-point increase in cortical amyloid-β SUVR. Subjective cognitive decline (CFI) attenuated the relationship between SUVR and STAI, while objective cognitive function (PACC) did not. No statistically significant relationship between SUVR and GDS was observed (p = 0.326).
Conclusions: In cognitively unimpaired adults with low levels of depression and anxiety, cortical amyloid-β deposition is associated with anxiety but not depressive symptoms. Attenuation of this relationship by subjective cognitive difficulties suggests that anxiety may be partly due to such a perception resulting from cortical amyloid-β deposition.
C.K. Lewis ; O.M. Bernstein ; J.D. Grill ; D.L. Gillen ; D.L. Sultzer (2022): Anxiety and Depressive Symptoms and Cortical Amyloid-β Burden in Cognitively Unimpaired Older Adults. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2022.13
DUAL TASK PERFORMANCE IS ASSOCIATED WITH AMYLOIDOSIS IN COGNITIVELY HEALTHY ADULTS
J.K. Longhurst, J.L. Cummings, S.E. John, B. Poston, J.V. Rider, A.M. Salazar, V.R. Mishra, A. Ritter, J.Z. Caldwell, J.B. Miller, J.W. Kinney, M.R. Landers
J Prev Alz Dis 2022;2(9):297-305Show summaryHide summary
Background: Preclinical Alzheimer’s disease (AD) provides an opportunity for the study and implementation of interventions and strategies aimed at delaying, mitigating, and preventing AD. While this preclinical state is an ideal target, it is difficult to identify efficiently and cost-effectively. Recent findings have suggested that cognitive-motor dual task paradigms may provide additional inference.
OBJECTIVES: Investigate the relationship between dual task performance and amyloidosis, suggestive of preclinical Alzheimer’s disease and whether dual task performance provides additional information beyond a cognitive composite, to help in the identification of amyloidosis.
SETTING: Outpatient specialty brain health clinical research institution in the United States.
PARTICIPANTS: 52 cognitively healthy adults.
MEASUREMENTS: The data included demographics, amyloid standardized uptake value ratio obtained via florbetapir-PET, neuropsychological testing, apolipoprotien E genotype, and dual task performance measures. Data were analyzed via hierarchal multiple linear regression or logistic regression, controlling for age, education, and apolipoprotien E genotype. Receiver operating characteristic curves were plotted, and sensitivity and specificity calculated via 2x2 contingency tables.
RESULTS: There was a moderate relationship (rs>.30) between motor and cognitive dual task effects and amyloid standardized uptake value ratio (ps<.042). A strong relationship (r=.58) was found between combined dual task effect, a measure of automaticity derived from dual task performance, and amyloid standardized uptake value ratio (p<.001). Additionally, combined dual task effect showed promise in its unique contributions to amyloid standardized uptake value ratio, accounting for 7.8% of amyloid standardized uptake value ratio variance beyond cognitive composite scores (p=.018). Additionally, when incorporated into the cognitive composite, combined dual task effect resulted in improved diagnostic accuracy for determining elevated amyloid standardized uptake value ratio, and increased the sensitivity and specificity of the cognitive composite.
CONCLUSSION: Dual task performance using the combined dual task effect, a measure of automaticity, was a moderate predictor of cerebral amyloidosis, which suggests that it has utility in the screening and diagnosis of individuals for preclinical AD. Additionally, when combined with the cognitive composite, the combined dual task effect improves diagnostic accuracy. Further research is warranted.
J.K. Longhurst ; J.L. Cummings ; S.E. John ; B. Poston ; J.V. Rider ; A.M. Salazar ; V.R. Mishra ; A. Ritter ; J.Z. Caldwell ; J.B. Miller ; J.W. Kinney ; M.R. Landers ; (2022): Dual Task Performance Is Associated with Amyloidosis in Cognitively Healthy Adults. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2022.1
DISEASE BURDEN AND ATTRIBUTABLE RISK FACTORS OF ALZHEIMER’S DISEASE AND DEMENTIA IN CHINA FROM 1990 TO 2019
R. Li, J. Qi, Y. Yang, Y. Wu, P. Yin, M. Zhou, Z. Qian, M.H. LeBaig, S.E. McMillin, H. Guo, H. Lin
J Prev Alz Dis 2022;2(9):306-314Show summaryHide summary
Background: Updated information on the burden of Alzheimer’s disease and other forms of dementia are of great importance for evidence-based health care planning. However, such an estimate has been lacking in Chinese populations at both national and provincial levels.
Objective: To estimate the temporal trends and the attributable burdens of selected risk factors of Alzheimer’s disease and other forms of dementia in China.
Design, Setting, and Participants: This is an observational description of the Global Burden of Diseases Study 2019 (GBD 2019). Data on incidence, mortality, prevalence, disability-adjusted life years (DALYs), years lived with disability (YLDs), and years of life lost (YLLs) of Alzheimer’s disease and other forms of dementia were derived from the GBD 2019 study at both national and provincial levels in China.
Measurements: Six indicators were used: incidence, mortality, prevalence, DALYs, YLLs, and YLDs. Absolute numbers in detail by age, sex, region, and age-standardized rates (with 95% uncertainty intervals) were calculated.
Results: There were notable increasing trends in the number of deaths (247·9%), incidence (264·8%), prevalence (296·5%), DALYs (228·1%), YLDs (308·7%) and YLLs (201·7%) from 1990 to 2019, respectively. The corresponding age-standardized rates increased by 6·2%, 19·3%, 33·6%, 10·7%, 33·4% and 3·1%. Smoking, high body mass index, high fasting plasma glucose levels, and metabolic risks were the four leading risk factors. Higher burden was observed among females versus males and in the more developed regions.
Conclusions: The disease burden in China were increasing substantially. Regional differences of the disease burden are accompanied by discrepancies of economic level and geographical location, as well as different levels of exposure to risk factors. Targeted prevention and control strategies are urgently needed to reduce the disease burden.
R. Li ; J. Qi ; Y. Yang ; Y. Wu ; P. Yin ; M. Zhou ; Z. Qian ; M.H. LeBaige ; S.E. McMillin ; H. Guo ; H. Lin (2021): Disease Burden and Attributable Risk Factors of Alzheimer’s Disease and Dementia in China from 1990 to 2019. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2021.69
THE ASSOCIATION OF HEART/VASCULAR AGING WITH MILD COGNITIVE IMPAIRMENT IN A RURAL MULTIETHNIC COHORT: THE PROJECT FRONTIER STUDY
D. Appiah, G. Ashworth, A. Boles, N. Nair
J Prev Alz Dis 2022;2(9):315-322Show summaryHide summary
BACKGROUND: Cardiovascular disease (CVD) and Alzheimer’s disease and related dementias (ADRD) disproportionately affect rural communities. Identifying strategies to effectively communicate CVD risk to prevent these conditions remains a high priority.
OBJECTIVE: We assessed the relation between predicted heart/vascular age (PHA), an easily communicated metric of CVD risk, and mild cognitive impairment (MCI), an early manifestation of ADRD.
DESIGN, SETTING, PARTICIPANTS: Data were from 967 rural West Texas residents aged ≥40 years without CVD at baseline (2009-2012) enrolled in Project FRONTIER, an ongoing, multi-ethnic cohort study on cognitive aging.
MEASUREMENTS: MCI was diagnosed using the standardized consensus review criteria. PHA was calculated using the Framingham CVD risk equation. High excess PHA (HEPHA) was defined as the difference between PHA and chronological age >5 years. Logistic regression models were used to calculate odds ratios (OR) and 95% confidence intervals (CI).
RESULTS: At baseline, the mean age of participants (70% women and 64% Hispanics) was 55 years. Almost 13% had MCI and 65% had HEPHA. After adjusting for socio-demographic and health factors, HEPHA was positively associated with MCI (OR=2.98; 95%CI: 1.72-5.15). Among participants without MCI at baseline who returned for follow-up exam after three years (n=238), a three-year negative change in PHA was seemingly associated with reduced odds for MCI (OR=0.98; 95%CI: 0.96-1.01).
CONCLUSIONS: In this study, PHA was positively associated with MCI, with improvement in CVD risk profile seemingly related to reduced odds for MCI. PHA may provide a low-cost means of communicating CVD risk in rural settings to prevent both CVD and ADRD.
D. Appiah ; G. Ashworth ; A. Boles ; N. Nair ; (2022): The Association of Heart/Vascular Aging with Mild Cognitive Impairment in a Rural Multiethnic Cohort: The Project FRONTIER Study. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2022.15
THE ASSOCIATION BETWEEN SUGAR-SWEETENED BEVERAGES AND COGNITIVE FUNCTION IN MIDDLE-AGED AND OLDER PEOPLE: A META-ANALYSIS
Q. Sun, Y. Yang, X. Wang, R. Yang, X. Li
J Prev Alz Dis 2022;2(9):323-330Show summaryHide summary
Objective: To explore the association between the intake of sugar-sweetened beverages and cognitive dysfunction in middle-aged and older adults, so as to provide an evidence-based basis for the early prevention of cognitive dysfunction.
Methods: A comprehensive search of relevant literature was conducted in PubMed, EMBase, Cochrane, ScienceDirect, and Web of Science from the inception until January 2021. Odds ratios (OR), hazard ratios (HR) and 95% confidence intervals (CI) were calculated using a random-effects, generic inverse variance method. Meta-analysis of the included studies was performed using Review Manager 5.4.
Results: A total of 10 studies on the association between sugary beverages and cognitive dysfunction in middle-aged and older adults were included, of which 3 were cross-sectional studies and the rest were cohort studies. Eight of the ten studies had results suggestive of a negative association. However, Meta-analysis results showed that the association between the intake of sugar-sweetened beverages and the risk of cognitive impairment was not statistically significant (OR=1.59, 95% CI: 0.93-2.74, P=0.08); but from two studies, the hazard ratios of all-cause dementia in middle-aged and older people consuming sugar-sweetened beverages was 2.77 (95%CI: 2.24-3.43, P<0.00001); the hazard ratios of Alzheimer’s disease in middle-aged and older people consuming sugar-sweetened beverages was 2.63 (95%CI: 1.70-4.05, P<0.0001).
Conclusion: There is insufficient evidence to state conclusively that sugar-sweetened beverages intake causes cognitive dysfunction in middle-aged and older adults.
Q. Sun ; Y. Yang ; X. Wang ; R. Yang ; X. Li (2021): The Association between Sugar-Sweetened Beverages and Cognitive Function in Middle-Aged and Older People: A Meta-Analysis. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2021.71
PLASMA MMP-9 LEVELS AS THE FUTURE RISK OF CONVERSION TO DEMENTIA IN APOE4-POSITIVE MCI PATIENTS: INVESTIGATION BASED ON THE ALZHEIMER’S DISEASE NEUROIMAGING INITIATIVE DATABASE
K. Abe, Y. Chiba, K. Ide, A. Yoshimi, T. Asami, A. Suda, T. Odawara, A. Hishimoto
J Prev Alz Dis 2022;2(9):331-337Show summaryHide summary
Background: Matrix metalloproteinase 9 (MMP-9) has been reported to be correlated with declines in hippocampal volume and cognitive function in ApoE4-positive MCI patients.
Objectives: The present study was aimed to investigate the effects of plasma matrix MMP-9 on the conversion risk between mild cognitive impairment (MCI) patients with and without ApoE4.
Design and setting: Retrospective observational study using the data extracted from the Alzheimer’s Disease Neuroimaging Initiative database.
Participants: We included 211 ApoE4-positive MCI subjects (ApoE4+ MCI) and 184 ApoE4-negative MCI subjects (ApoE4- MCI).
Measurements: We obtained demographic and data including plasma MMP-9 levels at baseline and longitudinal changes in Clinical Dementia Rating (CDR) up to 15 years. We compared conversion rates between ApoE4+ MCI and ApoE4- MCI by the Log-rank test and calculated the hazard ratio (HR) for covariates including age, sex, educational attainment, drinking and smoking histories, medications, and plasma MMP-9 levels using a multiple Cox regression analysis of ApoE4+ MCI and ApoE4- MCI.
Results: No significant differences were observed in baseline plasma MMP-9 levels between ApoE4+ MCI and ApoE4- MCI. High plasma MMP-9 levels increased the conversion risk significantly more than low plasma MMP-9 levels (HR, 2.46 [95% CI, 1.31-4.48]) and middle plasma MMP-9 levels (HR, 1.67 [95% CI, 1.04-2.65]) in ApoE4+ MCI, but not in ApoE4- MCI.
Conclusion: Plasma MMP-9 would be the risk of the future conversion to dementia in ApoE4+ MCI.
K. Abe ; Y. Chiba ; K. Ide ; A. Yoshimi ; T. Asami ; A. Suda ; T. Odawara ; A. Hishimoto (2022): Plasma MMP-9 Levels as the Future Risk of Conversion to Dementia in ApoE4-Positive MCI Patients: Investigation Based on the Alzheimer’s Disease Neuroimaging Initiative Database. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2022.19
EVALUATION OF MEMANTINE IN AAV-AD RAT: A MODEL OF LATEONSET ALZHEIMER’S DISEASE PREDEMENTIA
B. Souchet, M. Audrain, S. Alves, R. Fol, S. Tada, N.S Orefice, B. Potier, P. Dutar, J.-M. Billard, N. Cartier, J. Braudeau
J Prev Alz Dis 2022;2(9):338-347Show summaryHide summary
Background: Though our understanding of Alzheimer’s disease (AD) remains elusive, it is well known that the disease starts long before the first signs of dementia. This is supported by the large number of symptomatic drug failures in clinical trials and the increased trend to enroll patients at predementia stages with either mild or no cognitive symptoms. However, the design of pre-clinical studies does not follow this attitude, in particular regarding the choice of animal models, often irrelevant to mimic predementia Late Onset Alzheimer’s Disease (LOAD).
OBJECTIVES: We aimed to pharmacologically validate the AAV-AD rat model to evaluate preventive treatment of AD.
METHODS: We evaluated an N-methyl-D-aspartate receptor antagonist, named memantine, in AAV-AD rats, an age-dependent amyloid rat model which closely mimics Alzheimer’s pathology including asymptomatic and prodromal stages. Memantine was used at a clinically relevant dose (20 mg daily oral administration) from 4 (asymptomatic phase) to 10 (mild cognitive impairment phase) months of age.
RESULTS: A 6-month treatment with memantine promoted a non-amyloidogenic cleavage of APP followed by a decrease in soluble Aβ42. Consequently, both long-term potentiation and cognitive impairments were prevented. By contrast, the levels of hyperphosphorylated endogenous tau remained unchanged, indicating that a long-term memantine treatment is ineffective to restrain the APP processing-induced tauopathy.
CONCLUSIONS: Together, our data confirm that relevant models to LOAD, such as the AAV-AD rat, can provide a framework for a better understanding of the disease and accurate assessment of preventive treatments.
B. Souchet ; M. Audrain ; S. Alves ; R. Fol ; S. Tada ; N.S Orefice ; B. Potier ; P. Dutar ; J.-M. Billard ; N. Cartier ; J. Braudeau ; (2021): Evaluation of Memantine in AAV-AD Rat: A Model of Late-Onset Alzheimer’s Disease Predementia. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2021.67
THE SCOTTISH BRAIN HEALTH SERVICE MODEL: RATIONALE AND SCIENTIFIC BASIS FOR A NATIONAL CARE PATHWAY OF BRAIN HEALTH SERVICES IN SCOTLAND
C.W. Ritchie, J.M.J. Waymont, C. Pennington, K. Draper, A. Borthwick, N. Fullerton, M. Chantler, M.E. Porteous, S.O. Danso, A. Green, L. McWhirter, G. Muniz Terrera, S. Simpson, G. Thompson, D. Trépel, T.J. Quinn, A. Kilgour
J Prev Alz Dis 2022;2(9):348-358Show summaryHide summary
In order to address the oft-cited societal, economic, and health and social care impacts of neurodegenerative diseases, such as Alzheimer’s disease, we must move decisively from reactive to proactive clinical practice and to embed evidence-based brain health education throughout society. Most disease processes can be at least partially prevented, slowed, or reversed. We have long neglected to intervene in neurodegenerative disease processes, largely due to a misconception that their predominant symptom – cognitive decline – is a normal, age-related process, but also due to a lack of multi-disciplinary collaboration. We now understand that there are modifiable risk factors for neurodegenerative diseases, that successful management of common comorbidities (such as diabetes and hypertension) can reduce the incidence of neurodegenerative disease, and that disease processes begin (and, crucially, can be detected, reduced, and delayed, prevented, or treated) decades earlier in life than had previously been appreciated. Brain Health Scotland, established by Scottish Government and working in partnership with Alzheimer Scotland, propose far-reaching public health and clinical practice approaches to reduce neurodegenerative disease incidence. Focusing here on Brain Health Scotland’s clinical offerings, we present the Scottish Model for Brain Health Services. To our knowledge, the Scottish Model for Brain Health, built on foundations of personalised risk profiling, targeted risk reduction and prevention, early disease detection, equity of access, and harnessing comprehensive data to assist in clinical decision-making, marks the first example of a nationwide approach to overhauling clinical, societal, and political approaches to the prevention, assessment, and treatment of neurodegenerative disease.
C.W. Ritchie ; J.M.J. Waymont ; C. Pennington ; K. Draper ; A. Borthwick ; N. Fullerton ; M. Chantler ; M.E. Porteous ; S.O. Danso ; A. Green ; L. McWhirter ; G. Muniz Terrera ; S. Simpson ; G. Thompson ; D. Trépel ; T.J. Quinn ; A. Kilgour ; (2021): The Scottish Brain Health Service Model: Rationale and Scientific Basis for a National Care Pathway of Brain Health Services in Scotland. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2021.63
THE EFFECTS OF DUAL-TASK TRAINING ON COGNITIVE AND PHYSICAL FUNCTIONS IN OLDER ADULTS WITH COGNITIVE IMPAIRMENT; A SYSTEMATIC REVIEW AND META-ANALYSIS
N. Ali, H. Tian, L. Thabane, J. Ma, H. Wu, Q. Zhong, Y. Gao, C. Sun, Y. Zhu, T. Wang
J Prev Alz Dis 2022;2(9):359-370Show summaryHide summary
Background and objective: Individuals with Alzheimer disease and dementia experience cognitive decline and reduction in physical capabilities. Engaging in cognitive challenges and physical exercises is effective in reducing age-related cognitive and physical decline. It is believed that physical activity in the context of cognitive challenges might enhance the process of neurogenesis in the adult brain, but how effective are such interventions? Is there enough evidence to support that dual-task training is more effective than cognitive or physical training alone? To what extent can such training improve cognitive and physical functions in patients at various stages of cognitive decline?
Methodology: This systematic review with meta-analysis summarizes the emerging evidence of dual-task training for enhancing cognitive and physical functions in older individuals with cognitive impairment, dementia or Alzheimer’s disease. A systematic search was carried out in MEDLINE, PubMed, EMBASE, and Cochrane Library with the following search terms: randomized control trials, dual-task training, SCD, MCI, dementia, and Alzheimer’s disease.
Results: A total of 21 studies with 2,221 participants were identified. The results of dual-task tanning intervention are summarized as change in global cognitive function; SMD = 0.24, (P= 0.002), memory; SMD = 0.28, (P = 0.000), executive function; SMD = 0.35, (P = 0.000), attention; SMD = −0.19, (P = 0.1), gait speed; SMD = 0.26, (P = 0.007), dual-task cost; SMD 0.56, (P = 0.000), and balance; SMD 0.36, (P = 0.004).
Conclusion: Primary analysis showed a small-to-medium positive effect of dual-task training interventions on cognitive functions and medium-to-large positive effect on gait functions and balance.
N. Ali ; H. Tian ; L. Thabane ; J. Ma ; H. Wu ; Q. Zhong ; Y. Gao ; C. Sun ; Y. Zhu ; T. Wang (2022): The Effects of Dual-Task Training on Cognitive and Physical Functions in Older Adults with Cognitive Impairment; A Systematic Review and Meta-Analysis. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2022.16
IDENTIFYING DEMENTIA RISK IN OLDER VETERANS USING A MAILING SURVEY
A. Shah, O. Ysea-Hill, A. Torres-Morales, C.J. Gomez, A. Castellanos, J.G. Ruiz
J Prev Alz Dis 2022;2(9):371-375Show summaryHide summary
Evidence suggests that dementia can be prevented. Patients with frailty may be particularly at risk for cognitive impairment (CI). The aim of this study was to determine dementia risk in older Veterans and whether the risk varies according to frailty status. We also evaluated the feasibility of mailed dementia risk screening. Participants were mailed a questionnaire and the Self-Administered Gerocognitive Examination (SAGE). High dementia risk was defined as having mild cognitive impairment (MCI) on SAGE or a CAIDE score ≥6. Out of 5,432 mailed surveys, we obtained a response rate of 19.75%. Most responders completed the questionnaire items. We identified a total of 689 (75.9%) subjects to be at high risk for dementia. Individuals with frailty were at a greater risk for dementia when compared to robust individuals OR:1.921 (95%CI:1.259-2.930), p=.002. The mailed screening represents a convenient, alternative and scalable approach to screen for dementia risk.
A. Shah ; O. Ysea-Hill ; A. Torres-Morales ; C.J. Gomez ; A. Castellanos ; J.G. Ruiz ; (2022): Identifying Dementia Risk in Older Veterans Using A Mailing Survey. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2022.14
STUDY PROTOCOL OF A COMPREHENSIVE ACTIVITY PROMOTION
H. Shimada, S. Lee, K. Harada, S. Bae, K. Makino, I. Chiba, O. Katayama, H. Arai
J Prev Alz Dis 2022;2(9):376-384Show summaryHide summary
BACKGROUND: Several technical devices are available to monitor and promote changes in behavior toward higher activity. In particular, smartphones are becoming the primary platform for recognizing human activity. However, the effects of behavior change techniques that promote physical, cognitive, and social activities on incident dementia in older adults remain unknown.
Objectives: This randomized controlled trial aims to examine the effects of behavior change techniques on the prevention of dementia among community-dwelling older adults using a smartphone as a behavior change tool.
Design: A randomized controlled trial.
Setting: Community in Japan.
Participants: The study cohort comprises 3,498 individuals, aged ≥60 years, randomized into two groups: the smartphone group (n = 1,749) and the control group (n = 1,749).
Intervention. The smartphone group will be asked to use smartphone applications for at least 30 minutes daily to self-manage and improve their physical, cognitive, and social activities. The smartphone group will perform 60-minute group walking sessions using application-linked Nordic walking poles with cognitive stimulation twice a week during the intervention period. The walking poles are a dual-task exercise tool that works with a smartphone to perform cognitive tasks while walking, and the poles are equipped with switches to answer questions for simple calculation and memory tasks. The smartphone and control groups will receive lectures about general health that will be provided during the baseline and follow-up assessments.
Measurements: Incident dementia will be detected using cognitive tests (at baseline, after 15 months, and after 30 months) and by preparing diagnostic monthly reports based on data from the Japanese Health Insurance System. Participants without dementia at baseline who will be diagnosed with dementia over the 30-month follow-up period will be considered to have incident dementia.
Conclusions: This study has the potential to provide the first evidence of the effectiveness of information communication technology and Internet of Things in incident dementia. If our trial results show a delayed dementia onset for self-determination interventions, the study protocol will provide a cost-effective and safe method for maintaining healthy cognitive aging.
H. Shimada ; S. Lee ; K. Harada ; S. Bae ; K. Makino ; I. Chiba ; O. Katayama ; H. Arai ; (2022): Study Protocol of a Comprehensive Activity Promotion. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2022.12