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JPAD Volume 8, N°03 - 2021

 

NEW HOPE FOR ALZHEIMER’S DISEASE

B. Vellas, P. Aisen

J Prev Alz Dis 2021;3(8):238-239

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CITATION:
B. Vellas ; P. Aisen ; (2021): New Hope for Alzheimer’s Disease. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2021.26

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INTRANASAL INSULIN REDUCES WHITE MATTER HYPERINTENSITY PROGRESSION IN ASSOCIATION WITH IMPROVEMENTS IN COGNITION AND CSF BIOMARKER PROFILES IN MILD COGNITIVE IMPAIRMENT AND ALZHEIMER’S DISEASE

D. Kellar, S.N. Lockhart, P. Aisen, R. Raman, R.A. Rissman, J. Brewer, S. Craft

J Prev Alz Dis 2021;3(8):240-248

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Background: Intranasally administered insulin has shown promise in both rodent and human studies in Alzheimer’s disease; however, both effects and mechanisms require elucidation. Objective: We assessed the effects of intranasally administered insulin on white matter health and its association with cognition and cerebral spinal fluid biomarker profiles in adults with mild cognitive impairment or Alzheimer’s disease in secondary analyses from a prior phase 2 clinical trial (NCT01767909). Design: A randomized (1:1) double-blind clinical trial. Setting: Twelve sites across the United States. Participants: Adults with mild cognitive impairment or Alzheimer’s disease. Intervention: Participants received either twice daily placebo or insulin (20 IU Humulin R U-100 b.i.d.) intranasally for 12 months. Seventy-eight participants were screened, of whom 49 (32 men) were enrolled. Measurements: Changes from baseline in global and regional white matter hyperintensity volume and gray matter volume were analyzed and related to changes in cerebral spinal fluid biomarkers, Alzheimer’s Disease Assessment Scale-Cognition, Clinical Disease Rating-Sum of Boxes, Alzheimer’s Disease Cooperative Study–Activities of Daily Living Scale, and a memory composite. Results: The insulin-treated group demonstrated significantly reduced changes in white matter hyperintensity volume in deep and frontal regions after 12 months, with a similar trend for global volume. White matter hyperintensity volume progression correlated with worsened Alzheimer’s disease cerebral spinal fluid biomarker profile and cognitive function; however, patterns of correlations differed by treatment group. Conclusion: Intranasal insulin treatment for 12 months reduced white matter hyperintensity volume progression and supports insulin’s potential as a therapeutic option for Alzheimer’s disease.

CITATION:
D. Kellar ; S.N. Lockhart ; P. Aisen ; R. Raman ; R.A. Rissman ; J. Brewer ; S. Craft (2021): Intranasal Insulin Reduces White Matter Hyperintensity Progression in Association with Improvements in Cognition and CSF Biomarker Profiles in Mild Cognitive Impairment and Alzheimer’s Disease. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2021.14

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EFFECTS OF FOLIC ACID AND VITAMIN B12 SUPPLEMENTATION ON COGNITIVE IMPAIRMENT AND INFLAMMATION IN PATIENTS WITH ALZHEIMER’S DISEASE: A RANDOMIZED, SINGLE-BLINDED, PLACEBO-CONTROLLED TRIAL

H. Chen, S. Liu, B. Ge, D. Zhou, M. Li, W. Li, F. Ma, Z. Liu, Y. Ji, G. Huang

J Prev Alz Dis 2021;3(8):249-256

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Objectives: To evaluate the combined action of folic acid and vitamin B12 supplementation on cognitive performance and inflammation in patients with Alzheimer’s disease (AD). Design: This was a randomized, single-blind, placebo-controlled trial. Participants: Patients (n=120) diagnosed clinically as probable AD and in stable condition from Tianjin Key Laboratory of Cerebrovascular and Neurodegenerative Diseases. Measurements: Individuals were randomly divided into the intervention group (n=60, folic acid 1.2 mg/d + vitamin B12 50 μg/d) and the placebo group (n=60). Cognitive performance, blood folate, vitamin B12, one carbon cycle metabolite, and inflammatory cytokine levels were measured at baseline and after 6 months. The data were analyzed using linear mixed models for repeated measures. Results: A total of 101 participants (51 in the intervention group and 50 in the placebo group) completed the trial. Folic acid plus vitamin B12 supplementation had a beneficial effect on the MoCA total scores (P=0.029), naming scores (P=0.013), orientation scores (P=0.004), and ADAS-Cog domain score of attention (P=0.008), as compared to those of the control subjects. Moreover, supplementation significantly increased plasma SAM (P<0.001) and SAM/SAH (P<0.001), and significantly decreased the levels of serum Hcy (P<0.001), plasma SAH (P<0.001), and serum TNFα (P<0.001) compared to in the control subjects. Conclusions: Folic acid and vitamin B12 supplementation showed a positive therapeutic effect in AD patients who were not on a folic acid-fortified diet. The findings of this study help to delineate nutrient intervention as far as public health management for the prevention of dementia is concerned.

CITATION:
H. Chen ; S. Liu ; B. Ge ; D. Zhou ; M. Li ; W. Li ; F. Ma ; Z. Liu ; Y. Ji3 ; G. Huang (2021): Effects of Folic Acid and Vitamin B12 Supplementation on Cognitive Impairment and Inflammation in Patients with Alzheimer’s Disease: A Randomized, Single-Blinded, Placebo-Controlled Trial. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2021.22

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ITEM-LEVEL INVESTIGATION OF PARTICIPANT AND STUDY PARTNER REPORT ON THE COGNITIVE FUNCTION INDEX FROM THE A4 STUDY SCREENING DATA

R.E. Amariglio, S.A.M. Sikkes, G.A. Marshall, R.F. Buckley, J.R. Gatchel, K.A. Johnson, D.M. Rentz, M.C. Donohue, R. Raman, C.-K. Sun, R. Yaari , K.C. Holdridge, J.R. Sims, J.D. Grill, P.S. Aisen, R.A. Sperling

J Prev Alz Dis 2021;3(8):257-262

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Background: Greater subjective cognitive changes on the Cognitive Function Index (CFI) was previously found to be associated with elevated amyloid (Aß) status in participants screening for the A4 Study, reported by study partners and the participants themselves. While the total score on the CFI related to amyloid for both sources respectively, potential differences in the specific types of cognitive changes reported by either participants or their study partners was not investigated. Objectives: To determine the specific types of subjective cognitive changes endorsed by participants and their study partners that are associated with amyloid status in individuals screening for an AD prevention trial. Design, Setting, Participants: Four thousand four hundred and eighty-six cognitively unimpaired (CDR=0; MMSE 25-30) participants (ages 65-85) screening for the A4 Study completed florbetapir (Aß) Positron Emission Tomography (PET) imaging. Participants were classified as elevated amyloid (Aß+; n=1323) or non-elevated amyloid (Aß-; n=3163). Measurements: Prior to amyloid PET imaging, subjective report of changes in cognitive functioning were measured using the CFI (15 item questionnaire; Yes/Maybe/No response options) and administered separately to both participants and their study partners (i.e., a family member or friend in regular contact with the participant). The impact of demographic factors on CFI report was investigated. For each item of the CFI, the relationship between Aß and CFI response was investigated using an ordinal mixed effects model for participant and study partner report. Results: Independent of Aß status, participants were more likely to report ‘Yes’ or ‘Maybe’ compared to the study partners for nearly all CFI items. Older age (r= 0.06, p<0.001) and lower education (r=-0.08, p<0.001) of the participant were associated with higher CFI. Highest coincident odds ratios related to Aß+ for both respondents included items assessing whether ‘a substantial decline in memory’ had occurred in the last year (ORsp= 1.35 [95% CI 1.11, 1.63]; ORp= 1.55 [95% CI 1.34, 1.79]) and whether the participant had ‘seen a doctor about memory’ (ORsp= 1.56 [95% CI 1.25, 1.95]; ORp =1.71 [95% CI 1.37, 2.12]). For two items, associations were significant for only study partner report; whether the participant ‘Repeats questions’ (ORsp = 1.30 [95% CI 1.07, 1.57]) and has ‘trouble following the news’ (ORsp= 1.46[95% CI 1.12, 1.91]). One question was significant only for participant report; ‘trouble driving’ (ORp= 1.25 [95% CI 1.04, 1.49]). Conclusions: Elevated Aβ is associated with greater reporting of subjective cognitive changes as measured by the CFI in this cognitively unimpaired population. While participants were more likely than study partners to endorse change on most CFI items, unique CFI items were associated with elevated Aß for participants and their study partners, supporting the value of both sources of information in clinical trials.

CITATION:
R.E. Amariglio ; S.A.M. Sikkes ; G.A. Marshall ; R.F. Buckley ; J.R. Gatchel ; K.A. Johnson ; D.M. Rentz ; M.C. Donohue ; R. Raman ; C.-K. Sun ; R. Yaari ; K.C. Holdridge ; J.R. Sims ; J.D. Grill ; P.S. Aisen ; R.A. Sperling (2021): Item-Level Investigation of Participant and Study Partner Report on the Cognitive Function Index from the A4 Study Screening Data. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2021.8

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ENVIRONMENTAL DISTRACTIONS DURING UNSUPERVISED REMOTE DIGITAL COGNITIVE ASSESSMENT

E.N. Madero, J. Anderson, N.T. Bott, A. Hall, D. Newton, N. Fuseya, J.E. Harrison, J.R. Myers, J.M. Glenn

J Prev Alz Dis 2021;3(8):263-266

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The current demand for cognitive assessment cannot be met with traditional in-person methods, warranting the need for remote unsupervised options. However, lack of visibility into testing conditions and effort levels limit the utility of existing remote options. This retrospective study analyzed the frequency of and factors associated with environmental distractions during a brief digital assessment taken at home by 1,442 adults aged 23-84. Automated scoring algorithms flagged low data capture. Frequency of environmental distractions were manually counted on a per-frame and per-trial basis. A total of 7.4% of test administrations included distractions. Distractions were more frequent in men (41:350) than women (65:1,092) and the average age of distracted participants (51.7) was lower than undistracted participants (57.8). These results underscore the challenges associated with unsupervised cognitive assessment. Data collection methods that enable review of testing conditions are needed to confirm quality, usability, and actionability.

CITATION:
E.N. Madero ; J. Anderson ; N.T. Bott ; A. Hall ; D. Newton ; N. Fuseya ; J.E. Harrison ; J.R. Myers ; J.M. Glenn (2021): Environmental Distractions during Unsupervised Remote Digital Cognitive Assessment . The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2021.9

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CURRENT STATE OF SELF-ADMINISTERED BRIEF COMPUTERIZED COGNITIVE ASSESSMENTS FOR DETECTION OF COGNITIVE DISORDERS IN OLDER ADULTS: A SYSTEMATIC REVIEW

E. Tsoy, S. Zygouris, K.L. Possin

J Prev Alz Dis 2021;3(8):267-276

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Early diagnosis of cognitive disorders in older adults is a major healthcare priority with benefits to patients, families, and health systems. Rapid advances in digital technology offer potential for developing innovative diagnostic pathways to support early diagnosis. Brief self-administered computerized cognitive tools in particular hold promise for clinical implementation by minimizing demands on staff time. In this study, we conducted a systematic review of self-administered computerized cognitive assessment measures designed for the detection of cognitive impairment in older adults. Studies were identified via a systematic search of published peer-reviewed literature across major scientific databases. All studies reporting on psychometric validation of brief (≤30 minutes) self-administered computerized measures for detection of MCI and all-cause dementia in older adults were included. Seventeen studies reporting on 10 cognitive tools met inclusion criteria and were subjected to systematic review. There was substantial variability in characteristics of validation samples and reliability and validity estimates. Only 2 measures evaluated feasibility and usability in the intended clinical settings. Similar to past reviews, we found variability across measures with regard to psychometric rigor and potential for widescale applicability in clinical settings. Despite the promise that self-administered cognitive tests hold for clinical implementation, important gaps in scientific rigor in development, validation, and feasibility studies of these measures remain. Developments in technology and biomarker studies provide potential avenues for future directions on the use of digital technology in clinical care.

CITATION:
E. Tsoy ; S. Zygouris ; K.L. Possin (2021): Current State of Self-Administered Brief Computerized Cognitive Assessments for Detection of Cognitive Disorders in Older Adults: A Systematic Review. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2021.11

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ASSOCIATION OF SUBJECTIVE COGNITIVE DECLINE WITH RISK OF COGNITIVE IMPAIRMENT AND DEMENTIA: A SYSTEMATIC REVIEW AND META-ANALYSIS OF PROSPECTIVE LONGITUDINAL STUDIES

X.-T. Wang, Z.-T. Wang, H.-Y. Hu, Y. Qu, M. Wang, X.-N. Shen, W. Xu, Q. Dong, L. Tan, J.-T. Yu

J Prev Alz Dis 2021;3(8):277-285

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Background: Subjective cognitive decline (SCD) as an early pathological manifestation of brain aging has become more prevalent among older adults. Objectives: We aimed to investigate the associations of subjective cognitive decline (SCD) with the combined risk of cognitive impairment and dementia. Design: We performed a systematic review and meta-analysis via searching Embase, PubMed and Cochrane electronic databases from January 1 st 1970 to June 4th, 2020. Setting: Prospective cohort studies Participants: Healthy individuals were recruited from community, clinics and population. Measurements: Healthy individuals with SCD were classified into exposure groups, while those without were considered as the reference group. Adjusted relative risks (RR) were estimated in a random-effects model. Both primary and subgroup analyses were conducted. Results: Of 28,895 identified studies, 21 studies containing 22 cohorts were eligible for inclusion in the meta-analysis. SCD increased the risk of subsequent cognitive disorders (RR=2.12, 95% confidence intervals [CI] =1.75-2.58, I2=87%, P<0.01). To be specific, SCD conferred a 2.29-fold excess risk for cognitive impairment (RR=2.29, 95% CI=1.66-3.17, I2=83%, P<0.01) and a 2.16-fold excess risk for dementia (RR=2.16, 95% CI=1.63-2.86, I2=81%, P<0.01). In subgroup analyses, participants with SCD in the subgroup of 65-75 years old, long-education (>15 years) subgroup and subgroup of clinics showed a higher risk of developing objective cognitive disorders. Conclusions: SCD is associated with an increased combined risk of cognitive impairment and incident dementia and should be considered a risk factor for objective cognitive disorders.

CITATION:
X.-T. Wang ; Z.-T. Wang ; H.-Y. Hu ; Y. Qu ; M. Wang ; X.-N. Shen ; W. Xu ; Q. Dong ; L. Tan ; J.-T. Yu (2021): Association of Subjective Cognitive Decline with Risk of Cognitive Impairment and Dementia: A Systematic Review and Meta-Analysis of Prospective Longitudinal Studies. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2021.27

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THE INSTITUTE ON METHODS AND PROTOCOLS FOR ADVANCEMENT OF CLINICAL TRIALS IN ADRD (IMPACT-AD): A NOVEL CLINICAL TRIALS TRAINING PROGRAM

T. Berkness, M.C. Carrillo, R. Sperling, R. Petersen, P. Aisen, C. Flournoy, H. Snyder, R. Raman, J.D. Grill

J Prev Alz Dis 2021;3(8):286-291

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Background: Alzheimer’s Disease and Related Dementias (ADRD) clinical trials require multidisciplinary expertise in medicine, biostatistics, trial design, biomarkers, ethics, and informatics. Objectives: To provide focused interactive training in ADRD clinical trials to a diverse cadre of investigators. Design: The Institute on Methods and Protocols for Advancement of Clinical Trials in ADRD (IMPACT-AD) is a novel multidisciplinary clinical trial training program funded by the National Institute on Aging and the Alzheimer’s Association with two educational tracks. The Professionals track includes individuals who fill a broad variety of roles including clinicians, study coordinators, psychometricians, and other study professionals who wish to further their knowledge and advance their careers in ADRD trials. The Fellowship track includes current and future principal investigators and focuses on the design, conduct and analysis of ADRD clinical trials. Setting: The 2020 inaugural iteration of IMPACT-AD was held via Zoom. Participants: Thirty-five trainees (15 Fellowship track; 20 Professionals track) were selected from 104 applications (34% acceptance rate). Most (n=25, 71%) identified as female. Fifteen (43%) were of a non-white race; six (18%) were of Hispanic ethnicity; eight (23%) indicated they were the first person in their family to attend college. Measurements: Participants completed daily evaluations as well as pre- and post-course assessments of learning. Results: Across topic areas, >90% of trainees evaluated their change in knowledge based on the lectures as “very much” or “somewhat increased.” The mean proportion correct responses in pre- and post-course assessments increased from 55% to 75% for the Professionals track and from 54% to 78% for the Fellowship track. Conclusions: IMPACT-AD successfully launched a new training opportunity amid a global pandemic that preliminarily achieved the goals of attracting a diverse cohort and providing meaningful training. The course is funded through 2025.

CITATION:
T. Berkness ; M.C. Carrillo ; R. Sperling ; R. Petersen ; P. Aisen ; C. Flournoy ; H. Snyder ; R. Raman ; J.D. Grill (2021): The Institute on Methods and Protocols for Advancement of Clinical Trials in ADRD (IMPACT-AD): A Novel Clinical Trials Training Program. The Journal of Prevention of Alzheimer's Disease (JPAD). http://dx.doi.org/10.14283/jpad.2021.12

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MAIL AND TELEPHONE OUTREACH FROM ELECTRONIC HEALTH RECORDS FOR RESEARCH PARTICIPATION ON COGNITIVE HEALTH AND AGING

K. Pun, C.W. Zhu, M.T. Kinsella, M. Sewell, H. Grossman, J. Neugroschl, C. Li, A. Ardolino, N. Velasco, M. Sano

J Prev Alz Dis 2021;3(8):292-298

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Objectives: This report describes the efficacy and utility of recruiting older individuals by mail to participate in research on cognitive health and aging using Electronic Health Records (EHR). Methods: Individuals age 65 or older identified by EHR in the Mount Sinai Health System as likely to have Mild Cognitive Impairment (MCI) were sent a general recruitment letter (N=12,951). A comparison group of individuals with comparable age and matched for gender also received the letter (N=3,001). Results: Of the 15,952 individuals who received the mailing, 953 (6.0%) responded. 215 (1.3%) declined further contact. Overall rate of expression of interest was 4.6%. Of the 738 individuals who responded positively to further contact, 321 indicated preference for further contact by telephone. Follow-up of these individuals yielded 30 enrollments (0.2% of 15,952). No differences in response rate were noted between MCI and comparison groups, but the comparison group yielded higher enrollment. 6 individuals who were not the intended recipients of mailing but nevertheless contacted our study were also enrolled. Conclusions: Mailings to individuals identified through a trusted source, such as a medical center from which they have received clinical care, may be a viable means of reaching individuals within this age group as this effort yielded a low rejection rate. However, EHR information did not enhance study enrollment. Implications for improving recruitment are discussed.

CITATION:
K. Pun ; C.W. Zhu ; M.T. Kinsella ; M. Sewell ; H. Grossman ; J. Neugroschl ; C. Li ; A. Ardolino ; N. Velasco ; M. Sano (2021): Mail and Telephone Outreach from Electronic Health Records for Research Participation on Cognitive Health and Aging. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2021.18

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QUANTIFYING RECRUITMENT SOURCE AND PARTICIPANT COMMUNICATION PREFERENCES FOR ALZHEIMER’S DISEASE PREVENTION RESEARCH

D. Julbe-Delgado, J.L. O’Brien, R. Abdulkarim, E.M. Hudak, H. Maeda, J.D. Edwards

J Prev Alz Dis 2021;3(8):299-305

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Background: Evidence on effective engagement of diverse participants in AD prevention research is lacking. Objectives: To quantify recruitment source in relation to race, ethnicity, and retention. Design: Prospective cohort study. Setting: University lab. Participants: Participants included older adults (N=1170) who identified as White (86%), Black (8%), and Hispanic/Latino ethnicity (6%). Measurements: The Cognitive Aging Lab Marketing Questionnaire assessed recruitment source, social media use, and research opportunity communication preferences. Results: Effective recruitment methods and communication preferences vary by race and ethnicity. The most common referral sources were postcards for racial minorities, friend/family referrals for Hispanic/Latinos, and the newspaper for Whites. Whereas Whites preferred email communications, Hispanic/Latinos preferred texts. Conclusions: Recruiting diverse samples in AD prevention research is clinically relevant given high AD-risk of minorities and that health disparities are propagated by their under-representation in research. Our questionnaire and these results may be applied to facilitate effective research engagement.

CITATION:
D. Julbe-Delgado ; J.L. O’Brien ; R. Abdulkarim ; E.M. Hudak ; H. Maeda ; J.D. Edwards (2021): Quantifying Recruitment Source and Participant Communication Preferences for Alzheimer’s Disease Prevention Research. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2021.20

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PLATFORM TRIALS TO EXPEDITE DRUG DEVELOPMENT IN ALZHEIMER’S DISEASE: A REPORT FROM THE EU/US CTAD TASK FORCE

P.S. Aisen, R.J. Bateman, M. Carrillo, R. Doody, K. Johnson, J.R. Sims, R. Sperling, B. Vellas, and the EU/US CTAD Task Force

J Prev Alz Dis 2021;3(8):306-312

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A diverse range of platforms has been established to increase the efficiency and speed of clinical trials for Alzheimer’s disease (AD). These platforms enable parallel assessment of multiple therapeutics, treatment regimens, or participant groups; use uniform protocols and outcome measures; and may allow treatment arms to be added or dropped based on interim analyses of outcomes. The EU/US CTAD Task Force discussed the lessons learned from the Dominantly Inherited Alzheimer’s Network Trials Unit (DIAN-TU) platform trial and the challenges addressed by other platform trials that have launched or are in the planning stages. The landscape of clinical trial platforms in the AD space includes those testing experimental therapies such as DIAN-TU, platforms designed to test multidomain interventions, and those designed to streamline trial recruitment by building trial-ready cohorts. The heterogeneity of the AD patient population, AD drugs, treatment regimens, and analytical methods complicates the design and execution of platform trials, yet Task Force members concluded that platform trials are essential to advance the search for effective AD treatments, including combination therapies.

CITATION:
P.S. Aisen ; R.J. Bateman ; M. Carrillo ; R. Doody ; K. Johnson ; J.R. Sims ; R. Sperling ; B. Vellas ; and the EU/US CTAD Task Force ; (2021): Platform Trials to Expedite Drug Development in Alzheimer’s Disease: A Report from the EU/US CTAD Task Force. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2021.21

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THE EPIDEMIOLOGY OF ALZHEIMER’S DISEASE MODIFIABLE RISK FACTORS AND PREVENTION

X.-X. Zhang, Y. Tian, Z.-T. Wang, Y.-H. Ma, L. Tan, J.-T. Yu

J Prev Alz Dis 2021;3(8):313-321

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Mild Alzheimer’s disease is the leading cause of dementia, accounting for 50-70% of cases. Alzheimer’s disease is an irreversible neurodegenerative disease, which affects daily life activities and social functioning. As life expectancy increases and demographic ageing occurs, the global prevalence of Alzheimer’s disease is expected to continue to rise especially in developing countries, leading to a costly burden of disease. Alzheimer’s disease is a complex and multifactorial disorder that is determined by the interaction of genetic susceptibility and environmental factors across the life course. Epidemiological studies have identified potential modifiable risk and protective factors for Alzheimer’s disease prevention. Moreover, Alzheimer’s disease is considered to start decades earlier before clinical symptoms occur, thus interventions targeting several risk factors in non-demented elderly people even middle-aged population might prevent or delay Alzheimer’s disease onset. Here, we provide an overview of current epidemiological advances related to Alzheimer’s disease modifiable risk factors, highlighting the concept of early prevention.

CITATION:
X.-X. Zhang ; Y. Tian ; Z.-T. Wang ; Y.-H. Ma ; L. Tan ; J.-T. Yu (2021): The Epidemiology of Alzheimer’s Disease Modifiable Risk Factors and Prevention. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2021.15

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DETERMINANTS OF POST-OPERATIVE COGNITIVE DECLINE IN ELDERLY PEOPLE

J. Cartailler, C. Loyer, E. Vanderlynden, R. Nizard, C. Rabuel, L. Coblentz Baumann, C. Hourregue, J. Dumurgier, C. Paquet

J Prev Alz Dis 2021;3(8):322-328

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Background: Surgery and anesthesia can result in temporary or permanent deterioration of the cognitive functions, for which causes remain unclear. Objectives: In this pilot study, we analyzed the determinants of cognitive decline following a non-emergency elective prosthesis implantation surgery for hip or knee. Design: Prospective single-center study investigating psychomotor response time and changes in MoCA scores between the day before (D-1) and 2 days after (D+2) following surgery at the Lariboisière Hospital (Paris, France). Participants: 60 patients (71.9±7.1-year-old, 72% women) were included. Measurements: Collected data consisted in sociodemographic data, treatments, comorbidities and the type of anesthesia (local, general or both). Furthermore, we evaluated pain and well-being before as well as after the surgery using point scales. Results: Post-operative (D+2) MoCA scores were significantly lower than pre-operative ones (D-1) with a median difference of 2 pts [IQR]=4pts, (p<0.001), we found no significant difference between locoregional and general anesthesia. Pre-operative benzodiazepine or anticholinergic treatments were also associated to a drop in MoCA scores (p=0.006). Finally, the use of ketamine during anesthesia (p=0.043) and the well-being (p=0.006) evaluated before intervention, were both linked to a reduced cognitive impact. Conclusion: In this pilot study, we observed a post-operative short-term cognitive decline following a lower limb surgery. We also identified pre and perioperative independent factors linked to cognitive decline following surgery. In a next stage, a larger cohort should be used to confirm the impact of these factors on cognitive decline.

CITATION:
J. Cartailler ; C. Loyer ; E. Vanderlynden ; R. Nizard ; C. Rabuel ; L. Coblentz Baumann ; C. Hourregue ; J. Dumurgier ; C. Paquet (2021): Determinants of Post-Operative Cognitive Decline in Elderly People. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2021.13

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ELEVATED BLOOD HOMOCYSTEINE AND RISK OF ALZHEIMER’S DEMENTIA: AN UPDATED SYSTEMATIC REVIEW AND META-ANALYSIS BASED ON PROSPECTIVE STUDIES

M. Zuin, C. Cervellati, G. Brombo, A. Trentini, L. Roncon, G. Zuliani

J Prev Alz Dis 2021;3(8):329-334

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Objective: To investigate whether high serum homocysteine (Hcy) levels is associated with the risk of developing Alzheimer’s disease (AD) by performing a meta-analysis based on updated published data. Methods: We conducted a comprehensive research using Medline (Pubmed), Scopus, Web of Science and EMBASE databases to identify all prospective studies published any time to July 7, 2020 evaluating the association between elevated Hcy levels and AD risk. Results: From an initial screening of 269 published papers, 9 prospective investigations conducted on a total of 7474 subjects with mean follow-up of 9.5 years (range: 3.7-10) were included in the meta-analysis. Eight seventy-five of these subjects converted to AD. Hcy was significantly higher in these individuals (HRadjusted:1.48, 95% CI:1.23-1.76, I2=65.6%, p<0.0001) compared with who did not convert to AD. There was a significant publication bias (Egger’s test, t=6.39, p=0.0003) and this was overcome by the trim and fill method, which allowed to calculate a bias-corrected imputed risk estimate of HRadjusted:1.20, 95% CI:1.01-1.44, Q value=41.92. Conclusions: The present meta-analysis found that having higher Hcy increases the risk of AD in the elderly and this finding is consistent with the widely suggested role of this non-proteinogenic α-amino acid in AD neurodegeneration.

CITATION:
M. Zuin ; C. Cervellati ; G. Brombo ; A. Trentini ; L. Roncon ; G. Zuliani (2021): Elevated Blood Homocysteine and Risk of Alzheimer’s Dementia: An Updated Systematic Review and Meta-Analysis Based on Prospective Studies. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2021.7

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DEVELOPMENT, VALIDATION AND FIELD EVALUATION OF THE SINGAPORE LONGITUDINAL AGEING STUDY (SLAS) RISK INDEX FOR PREDICTION OF MILD COGNITIVE IMPAIRMENT AND DEMENTIA

T.P. Ng, T.S. Lee, W.S. Lim, M.S. Chong, P. Yap, C.Y. Cheong, K.B. Yap, I. Rawtaer, T.M. Liew, Q. Gao, X. Gwee, M.P.E. Ng, S.O. Nicholas, S.L. Wee

J Prev Alz Dis 2021;3(8):335-344

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Background: Mild cognitive impairment (MCI) is a critical pre-dementia target for preventive interventions. There are few brief screening tools based on self-reported personal lifestyle and health-related information for predicting MCI that have been validated for their generalizability and utility in primary care and community settings. Objective: To develop and validate a MCI risk prediction index, and evaluate its field application in a pilot community intervention trial project. Design: Two independent population-based cohorts in the Singapore Longitudinal Ageing Study (SLAS). We used SLAS1 as a development cohort to construct the risk assessment instrument, and SLA2 as a validation cohort to verify its generalizability. Setting: community-based screening and lifestyle intervention Participants: (1) SLAS1 cognitively normal (CN) aged ≥55 years with average 3 years (N=1601); (2) SLAS2 cohort (N=3051) with average 4 years of follow up. (3) 437 participants in a pilot community intervention project. Measurements: The risk index indicators included age, female sex, years of schooling, hearing loss, depression, life satisfaction, number of cardio-metabolic risk factors (wide waist circumference, pre-diabetes or diabetes, hypertension, dyslipidemia). Weighted summed scores predicted probabilities of MCI or dementia. A self-administered questionnaire field version of the risk index was deployed in the pilot community project and evaluated using pre-intervention baseline cognitive function of participants. Results: Risk scores were associated with increasing probabilities of progression to MCI-or-dementia in the development cohort (AUC=0.73) and with increased prevalence and incidence of MCI-or-dementia in the validation cohort (AUC=0.74). The field questionnaire risk index identified high risk individuals with strong correlation with RBANS cognitive scores in the community program (p<0.001). Conclusions: The SLAS risk index is accurate and replicable in predicting MCI, and is applicable in community interventions for dementia prevention.

CITATION:
T.P. Ng ; T.S. Lee ; W.S. Lim ; M.S. Chong ; P. Yap ; C.Y. Cheong ; K.B. Yap ; I. Rawtaer ; T.M. Liew ; Q. Gao ; X. Gwee ; M.P.E. Ng ; S.O. Nicholas ; S.L. Wee (2021): Development, Validation and Field Evaluation of the Singapore Longitudinal Ageing Study (SLAS) Risk Index for Prediction of Mild Cognitive Impairment and Dementia. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2021.19

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CHILDHOOD SECONDHAND SMOKE EXPOSURE AND RISK OF DEMENTIA, ALZHEIMER’S DISEASE AND STROKE IN ADULTHOOD: A PROSPECTIVE COHORT STUDY

S. Zhou, K. Wang

J Prev Alz Dis 2021;3(8):345-350

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Background: This study aimed to investigate the associations between secondhand smoke exposure and dementia, Alzheimer’s disease (AD) and stroke. Methods: This prospective study analyzed Framingham Offspring (FHS-OS) cohort participants with parents in the original Framingham Heart Study (FHS) cohort with known smoking status during offspring childhood. Surveillance for incident events, including dementia and stroke, among offspring participants exposed to parental smoking up to the age of 18 years commenced at examination 9 through 2014 and continued for approximately 30 years. Results: At baseline, a total of 1683 (56.2%) subjects were not exposed to any secondhand smoke, whereas 670 (22.4%) subjects were exposed to 0-1 packs (20 cigarettes)/day, and 640 (21.4%) were exposed to over 1 pack/day. On follow-up (median: 31 years), 2993 patients developed dementia, including 103 with AD dementia and 315 with stroke. After adjusting for a wide range of established risk factors, participants with the highest exposure to secondhand smoke exhibited increased risks of all dementia, AD dementia and stroke compared with individuals with no exposure [HR 2.86 (2.00-4.09) for dementia; HR 3.13 (1.80-5.42) for AD dementia; HR 1.89 (1.37-2.61) for stroke]. The results remained comparable in the subgroup for individuals with median exposure to secondhand smoke. Conclusion: Exposure to secondhand smoke may be associated with increased risks of dementia, AD dementia and stroke.

CITATION:
S. Zhou ; K. Wang ; (2021): Childhood Secondhand Smoke Exposure and Risk of Dementia, Alzheimer’s Disease and Stroke in Adulthood: A Prospective Cohort Study. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2021.10

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DETERMINANTS OF MEDICAL DIRECT COSTS OF CARE AMONG PATIENTS OF A MEMORY CENTER

V. Dauphinot, A. Garnier-Crussard, C. Moutet, F. Delphin-Combe, H.-M. Späth, P. Krolak-Salmon

J Prev Alz Dis 2021;3(8):351-361

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Background: Alzheimer’s disease and related diseases (ADRD) are a major cause of health-related cost increase. Objectives: This study aimed to estimate the real medical direct costs of care of patients followed at a memory center, and to investigate potential associations between patients’ characteristics and costs. Design: Cross-sectional analyses conducted on matched data between clinical data of a cohort of patients and the claims database of the French Primary Health Insurance Fund. Setting: Memory center in France Participants: Patients attending a memory center with subjective cognitive complaint Measurements: Medical or nonmedical direct costs (transportation) reimbursed by the French health insurance during the one year after the first memory visit, and socio-demographic, clinical, cognitive, functional, and behavioral characteristics were analyzed. Results: Among 2,746 patients (mean ± SD age 79.9 ± 8 years, 42.4% of patients with dementia), the total direct cost was on average € 9,885 per patient during the year after the first memory visit: € 7,897 for patients with subjective cognitive complaint, € 9,600 for patients with MCI, and € 11,505 for patients with dementia. A higher functional and cognitive impairment, greater behavioral disorders, and a higher caregiver burden were independently associated with a higher total direct cost. A one-point decrease in the Instrumental Activities of Daily Living score was associated with a € 1,211 cost increase. The cost was higher in patients with Parkinson’s disease, and Lewy body disease compared to patients with AD. Diabetes mellitus, anxiety disorders and number of drugs were also significantly associated with greater costs. Conclusions: Higher real medical direct costs were independently associated with cognitive, functional, and behavioral impairment, diabetes mellitus, anxiety disorders, number of drugs, etiologies as well as caregiver burden in patients attending a memory center. The identification of factors associated to higher direct costs of care offers additional direct targets to evaluate how interventions conducted in patients with NCD impact direct costs of care.

CITATION:
V. Dauphinot ; A. Garnier-Crussard ; C. Moutet ; F. Delphin-Combe ; H.-M. Späth ; P. Krolak-Salmon (2021): Determinants of Medical Direct Costs of Care among Patients of a Memory Center. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2021.16

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MAJOR COST DRIVERS IN ASSESSING THE ECONOMIC BURDEN OF ALZHEIMER’S DISEASE: A STRUCTURED, RAPID REVIEW

M. Kosaner Kließ, R. Martins, M.P. Connolly1

J Prev Alz Dis 2021;3(8):362-370

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Background: Alzheimer’s Disease is the most common cause of dementia, affecting memory, thinking and behavior. Symptoms eventually grow severe enough to interfere with daily tasks. AD is predicted to increase healthcare spending and costs associated with formal and informal caregiving. The aim of this study was to identify and quantify the contribution of the different cost components associated with AD. Methods: A structured literature review was conducted to identify studies reporting the economic burden of Alzheimer`s Disease beyond the healthcare setting. The search was conducted in Medline, Embase and EconLit and limited to studies published in the last 10 years. For each identified cost component, frequency weighted mean costs were calculated across countries to estimate the percentage contribution of each component by care setting and disease severity. Results obtained by each costing approach were also compared. Results: For community-dwelling adults, the percentage of healthcare, social care and indirect costs to total costs were 13.9%, 17.4% and 68.7%, respectively. The percentage of costs varied by disease severity with 26.0% and 10.4% of costs spent on healthcare for mild and severe disease, respectively. The proportion of total spending on indirect costs changed from 60.7% to 72.5% as disease progressed. For those in residential care, the contribution of each cost component was similar between moderate and severe disease. Social care accounted on average for 85.9% of total costs. Conclusion: The contribution of healthcare costs to the overall burden was not negligible; but was generally exceeded by social and informal care costs.

CITATION:
M. Kosaner Kließ ; R. Martins ; M.P. Connolly (2021): Major Cost Drivers in Assessing the Economic Burden of Alzheimer’s Disease: A Structured, Rapid Review. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2021.17

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DIAGNOSIS OF EARLY ALZHEIMER’S DISEASE: CLINICAL PRACTICE IN 2021

A.P. Porsteinsson, R.S. Isaacson, S. Knox, M.N. Sabbagh, I. Rubino

J Prev Alz Dis 2021;3(8):371-386

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Alzheimer’s disease is a progressive, irreversible neurodegenerative disease impacting cognition, function, and behavior. Alzheimer’s disease progresses along a continuum from preclinical disease, to mild cognitive and/or behavioral impairment and then Alzheimer’s disease dementia. Recently, clinicians have been encouraged to diagnose Alzheimer’s earlier, before patients have progressed to Alzheimer’s disease dementia. The early and accurate detection of Alzheimer’s disease-associated symptoms and underlying disease pathology by clinicians is fundamental for the screening, diagnosis, and subsequent management of Alzheimer’s disease patients. It also enables patients and their caregivers to plan for the future and make appropriate lifestyle changes that could help maintain their quality of life for longer. Unfortunately, detecting early-stage Alzheimer’s disease in clinical practice can be challenging and is hindered by several barriers including constraints on clinicians’ time, difficulty accurately diagnosing Alzheimer’s pathology, and that patients and healthcare providers often dismiss symptoms as part of the normal aging process. As the prevalence of this disease continues to grow, the current model for Alzheimer’s disease diagnosis and patient management will need to evolve to integrate care across clinical disciplines and the disease continuum, beginning with primary care. This review summarizes the importance of establishing an early diagnosis of Alzheimer’s disease, related practical ‘how-to’ guidance and considerations, and tools that can be used by healthcare providers throughout the diagnostic journey.

CITATION:
A.P. Porsteinsson ; R.S. Isaacson ; S. Knox ; M.N. Sabbagh ; I. Rubino ; (2021): Diagnosis of Early Alzheimer’s Disease: Clinical Practice in 2021. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2021.23

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CAN VIRTUAL SCIENTIFIC CONFERENCES FACILITATE TWOWAY LEARNING BETWEEN DEMENTIA RESEARCHERS AND PARTICIPANTS?

S. Walter, B. Wheaton, C. Huling Hummel, J. Tyrone, J. Ziolkowski, E. Shaffer, N.T. Aggarwal

J Prev Alz Dis 2021;3(8):387-388

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CITATION:
S. Walter ; B. Wheaton ; C. Huling Hummel ; J. Tyrone ; J. Ziolkowski ; E. Shaffer ; N.T. Aggarwal (2021): Can Virtual Scientific Conferences Facilitate Two-Way Learning between Dementia Researchers and Participants?. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2021.24

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