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Results in Journal The Journal of Prevention of Alzheimer's Disease: 559

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, S. Andrieu, M. Pahor, C. Cantet, , P.J. Ousset, T. Voisin, B. Fougère, S. Gillette, I. Carrié, et al.
The Journal of Prevention of Alzheimer's Disease, pp 1-9; https://doi.org/10.14283/jpad.2016.94

Abstract:
Objectives: An international group proposed the existence of “cognitive frailty”, a condition defined by simultaneous presence of physical frailty and cognitive impairment in the absence of dementia. The objective was to compare the neuropsychological profiles in subgroups of elders differentiated across their physical frailty (Fried phenotype) and cognitive status (Clinical Dementia Rating score) to characterize the “cognitive frailty” entity. Method: We studied baseline characteristics of 1,617 subjects enrolled in Multidomain Alzheimer Disease Preventive Trial (MAPT). Included subjects were aged 70 years or older and presented at least 1 of the 3 following clinical criteria: (1) Memory complaint spontaneously reported to a general practitioner, (2) limitation in one instrumental activity of daily living, (3) slow gait speed. Subjects with dementia were not included in the trial. Results: “Cognitive frailty individuals” significantly differed from “individuals with cognitive impairment and without physical frailty”, scoring worse at executive, and attention tests. They presented subcortico-frontal cognitive pattern different of Alzheimer Disease. Cognitive performance of subjects with 3 criteria or more of the frailty phenotype are cognitively more impaired than subjects with only one. Discusion: The characterization of “cognitive frailty” must be done in frail subjects to set up specific preventive clinical trials for this population.
, G.A. Laughlin, D. Kritz-Silverstein, E. Barrett-Connor, L.K. McEvoy
The Journal of Prevention of Alzheimer's Disease, pp 1-9; https://doi.org/10.14283/jpad.2016.89

Abstract:
Background: Evidence suggests that moderate alcohol consumption may protect against cognitive decline and dementia. However, uncertainty remains over the patterns of drinking that are most beneficial. Objective: To examine associations between amount and frequency of alcohol consumption with multiple domains of cognitive function in a well-characterized cohort of older community-dwelling adults in southern California. Design: Observational, cross-sectional cohort study. Setting: A research visit between 1988-1992 in Rancho Bernardo, California. Participants: 1624 participants of the Rancho Bernardo Study (mean age ± SD = 73.2 ± 9.3 years). Measurements: Participants completed a neuropsychological test battery, self-administered questionnaires on alcohol consumption and lifestyle, and a clinical health evaluation. We classified participants according to average amount of alcohol intake into never, former, moderate, heavy and excessive drinkers, and according to frequency of alcohol intake, into non-drinkers, rare, infrequent, frequent and daily drinkers. We examined the association between alcohol intake and cognitive function, controlling for age, sex, education, exercise, smoking, waist-hip ratio, hypertension and self-assessed health. Results: Amount and frequency of alcohol intake were significantly associated with cognitive function, even after controlling for potentially related health and lifestyle variables. Global and executive function showed positive linear associations with amount and frequency of alcohol intake, whereas visual memory showed an inverted U-shaped association with alcohol intake, with better performance for moderate and infrequent drinkers than for non-drinkers, excessive drinkers or daily drinkers. Conclusions: In several cognitive domains, moderate, regular alcohol intake was associated with better cognitive function relative to not drinking or drinking less frequently. This suggests that beneficial cognitive effects of alcohol intake may be achieved with low levels of drinking that are unlikely to be associated with adverse effects in an aging population.
, M. Chandler Greenaway, N. Duncan, J.A. Fields, A.V. Cuc, C. Hoffman Snyder, S. Hanna, A. Lunde, G.E. Smith
The Journal of Prevention of Alzheimer's Disease, pp 1-8; https://doi.org/10.14283/jpad.2014.27

Abstract:
BACKGROUND: A major potential barrier for studying behavioral interventions for patients with Mild Cognitive Impairment (MCI) is the willingness and ability of people to enroll in and adhere to behavioral interventions, especially when the intervention involves dyads of patients with MCI and support partners. Details regarding recruitment strategies and processes (such as number of dyads screened) are often missing from reports of behavioral trials. In addition, reports do not detail the reasons a potentially eligible candidate opts out of participation in a research study. OBJECTIVES: To describe the challenges and successes of enrollment and retention in a behavioral trial for persons with MCI and their care partners, and to better understand barriers to participation from the patient’s point of view. DESIGN: Multi-site, randomized trial. SETTING: Major medical centers. PARTICIPANTS: Our accrual target for the study was 60 participants. Potential candidates were patients presenting to memory evaluation clinics whose resulting clinical diagnosis was MCI. A total of 200 consecutive potential candidates were approached about participating in the study across the three sites. INTERVENTION: Detailed recruitment and retention data of a randomized trial comparing two behavioral interventions (memory notebook training versus computer training) provided in two separate training time frames (10 days versus 6 weeks). MEASUREMENTS: Structured interview with those declining to participate in the trial. RESULTS: Overall recruitment 37% with a range of 13%-72% across sites. Overall retention 86% with a range of 74%-94% across sites. CONCLUSIONS: The primary barriers to enrollment from the patient’s perspective were distance to the treatment center and competing comprehensive behavioral programming. However, retention data suggest that those dyads who enroll in behavioral programs are highly committed.
, Sandrine Andrieu, Deborah Blacker, Aaron J Carman, Allan M Green, Francine Grodstein, Victor W Henderson, Bryan D. James, Rachel F Lane, Joseph Lau, et al.
The Journal of Prevention of Alzheimer's Disease, Volume 1, pp 117-123

Abstract:
Worldwide, over 35 million people suffer from Alzheimer’s disease and related dementias. This number is expected to triple over the next 40 years. How can we improve the evidence supporting strategies to reduce the rate of dementia in future generations? The risk of dementia is likely influenced by modifiable factors such as exercise, cognitive activity, and the clinical management of diabetes and hypertension. However, the quality of evidence is limited and it remains unclear whether specific interventions to reduce these modifiable risk factors can, in turn, reduce the risk of dementia. Although randomized controlled trials are the gold-standard for causality, the majority of evidence for long-term dementia prevention derives from, and will likely continue to derive from, observational studies. Although observational research has some unavoidable limitations, its utility for dementia prevention might be improved by, for example, better distinction between confirmatory and exploratory research, higher reporting standards, investment in effectiveness research enabled by increased data-pooling, and standardized exposure and outcome measures. Informed decision-making by the general public on low-risk health choices that could have broad potential benefits could be enabled by internet-based tools and decision-aids to communicate the evidence, its quality, and the estimated magnitude of effect.
, I. Carrie, S. Gillette-Guyonnet, J. Touchon, T. Dantoine, J.F. Dartigues, M.N. Cuffi, S. Bordes, Y. Gasnier, P. Robert, et al.
The Journal of Prevention of Alzheimer's Disease, Volume 1, pp 13-22

Abstract:
The Multidomain Alzheimer Preventive Trial (MAPT study) was designed to assess the efficacy of isolated supplementation with omega-3 fatty acid, an isolated multidomain intervention (consisting of nutritional counseling, physical exercise, cognitive stimulation) or a combination of the two interventions on the change of cognitive functions in frail subjects aged 70 years and older for a period of 3 years. Ancillary neuroimaging studies were additionally implemented to evaluate the impact of interventions on cerebral metabolism (FDG PET scans) and atrophy rate (MRIs), as well as brain amyloïd deposit (AV45 PET scans). 1680 subjects (mean age: 75.3 years; female: 64.8 %), enrolled by 13 memory clinics, were randomized into one of the following four groups: omega-3 supplementation alone, multidomain intervention alone, omega-3 plus multidomain intervention, or placebo. Participants underwent cognitive, functional and biological assessments at M6, M12, M24 and M36 visits. The primary endpoint is a change of memory function at 3 years, as assessed by the Free and Cued Selective Reminding test. All participants will be followed for 2 additional years after the 3-years intervention (MAPT PLUS extension study). 1/Omega-3 supplementation: two soft capsules daily as a single dose, containing a total of 400 mg docosahexaenoic acid (DHA), i.e., 800 mg docosahexaenoic acid per day, for 3 years. 2/ Multidomain intervention: collective training sessions conducted in small groups (6–8 participants) in twelve 120-minute sessions over the first 2 months (two sessions a week for the first month, and one session a week the second month) then a 60-minute session per month in the following three areas: nutrition, physical activity, and cognition until the end of the 3 years. In addition to the collective sessions, individualized preventive outpatient visits exploring possible risk factors for cognitive decline are performed at baseline, M12 and M24. For cognition, the mean MMSE at baseline was 28.1 (± 1.6). About 58% and 42% of participants had a CDR score equal to 0 and 0.5, respectively. Regarding mobility status, 200 (11.9%) had a 4-m gait speed lower or equal to 0.8 m/s. According to the Fried criteria, 673 (42.1%) participants were considered pre frail, and 51 (3.2%) frail. The red blood cell DHA content was 26.1 ± 8.1 µg/g. Five hundred and three participants underwent baseline MRI. AV45 PET scans were performed in 271 individuals and preliminary results showed that 38.0% had a cortical SUVR > 1.17, which gave an indication of significant brain amyloïd deposit. DISCUSSION: The MAPT trial is presently the first largest and longest multidomain preventive trial relevant to cognitive decline in older adults with subjective memory complaints. The multidomain intervention designed for the MAPT trial is likely to be easily implemented within the general population.
, J. Murray, W.H. Tsui, Y. Li, M. Davies, S. Williams, E. Pirraglia, N. Spector, R.S. Osorio, L. Glodzik, et al.
The Journal of Prevention of Alzheimer's Disease, Volume 1, pp 23-32

Abstract:
Epidemiological evidence linking diet, one of the most important modifiable environmental factors, and risk of Alzheimer's disease (AD) is rapidly increasing. Several studies have shown that higher adherence to a Mediterranean diet (MeDi) is associated with reduced risk of AD. This study examines the associations between high vs. lower adherence to a MeDi and structural MRI-based brain atrophy in key regions for AD in cognitively normal (NL) individuals with and without risk factors for AD. Cross-sectional study. Manhattan (broader area). Fifty-two NL individuals (age 54+12 y, 70% women) with complete dietary information and cross-sectional, 3D T1-weighted MRI scans were examined. Subjects were dichotomized into those showing higher vs. lower adherences to the MeDi using published protocols. Estimates of cortical thickness for entorhinal cortex (EC), inferior parietal lobe, middle temporal gyrus, orbitofrontal cortex (OFC) and posterior cingulate cortex (PCC) were obtained by use of automated segmentation tools (FreeSurfer). Multivariate general linear models and linear regressions assessed the associations of MeDi with MRI measures. Of the 52 participants, 20 (39%) showed higher MeDi adherence (MeDi+) and 32 (61%) showed lower adherence (MeDi-). Groups were comparable for clinical, neuropsychological measures, presence of a family history of AD (FH), and frequency of Apolipoprotein E (APOE) ε4 genotype. With and without controlling for age and total intracranial volume, MeDi+ subjects showed greater thickness of AD-vulnerable ROIs as compared to MeDi- subjects (Wilk's Lambda p=0.026). Group differences were most pronounced in OFC (p=0.001), EC (p=0.03) and PCC (p=0.04) of the left hemisphere. Adjusting for gender, education, FH, APOE status, BMI, insulin resistance scores and presence of hypertension did not attenuate the relationship. NL individuals showing lower adherence to the MeDi had cortical thinning in the same brain regions as clinical AD patients compared to those showing higher adherence. These data indicate that the MeDi may have a protective effect against tissue loss, and suggest that dietary interventions may play a role in the prevention of AD.
M. Berres, W.A Kukull, A.R. Miserez, A.U. Monsch, S.E Monsell,
The Journal of Prevention of Alzheimer's Disease, Volume 1, pp 99-109

Abstract:
The PGSA (Placebo Group Simulation Approach) aims at avoiding problems of sample representativeness and ethical issues typical of placebo-controlled secondary prevention trials with MCI patients. The PGSA uses mathematical modeling to forecast the distribution of quantified outcomes of MCI patient groups based on their own baseline data established at the outset of clinical trials. These forecasted distributions are then compared with the distribution of actual outcomes observed on candidate treatments, thus substituting for a concomitant placebo group. Here we investigate whether a PGSA algorithm that was developed from the MCI population of ADNI 1*, can reliably simulate the distribution of composite neuropsychological outcomes from a larger, independently selected MCI subject sample. Data available from the National Alzheimer’s Coordinating Center (NACC) were used. We included 1523 patients with single or multiple domain amnestic mild cognitive impairment (aMCI) and at least two follow-ups after baseline. In order to strengthen the analysis and to verify whether there was a drift over time in the neuropsychological outcomes, the NACC subject sample was split into 3 subsamples of similar size. The previously described PGSA algorithm for the trajectory of a composite neuropsychological test battery (NTB) score was adapted to the test battery used in NACC. Nine demographic, clinical, biological and neuropsychological candidate predictors were included in a mixed model; this model and its error terms were used to simulate trajectories of the adapted NTB. The distributions of empirically observed and simulated data after 1, 2 and 3 years were very similar, with some over-estimation of decline in all 3 subgroups. The by far most important predictor of the NTB trajectories is the baseline NTB score. Other significant predictors are the MMSE baseline score and the interactions of time with ApoE4 and FAQ (functional abilities). These are essentially the same predictors as determined for the original NTB score. An algorithm comprising a small number of baseline variables, notably cognitive performance at baseline, forecasts the group trajectory of cognitive decline in subsequent years with high accuracy. The current analysis of 3 independent subgroups of aMCI patients from the NACC database supports the validity of the PGSA longitudinal algorithm for a NTB. Use of the PGSA in long-term secondary AD prevention trials deserves consideration.
, W.J. Jagust
The Journal of Prevention of Alzheimer's Disease, pp 1-7; https://doi.org/10.14283/jpad.2015.47

Abstract:
Vascular risk factors (e.g. hypertension, dyslipidemia and diabetes) are well known risk factors for Alzheimer’ disease. These vascular risk factors lead to vascular brain injuries, which also increase the likelihood of dementia. The advent of amyloid PET imaging has helped establish that vascular risk factors also lead to Alzheimer’s disease via pathways that are independent from vascular brain injuries, at least, when vascular brain injuries are measured as white matter lesions and infarcts. While vascular brain injuries (white matter lesions and infarcts) do not seem to influence amyloid pathology, some evidence from amyloid imaging suggests that increased vascular risk is related to increased amyloid burden. Furthermore, while vascular brain injuries and amyloid have an additive and independent impact on brain integrity, vascular risk factors might potentiate the impact of amyloid on cortical thickness on brain regions vulnerable to Alzheimer’s disease. New research should further explore and confirm, or refute, possible interactions between amyloid and vascular risk factors on brain integrity and cognition. Neuroimaging tools used to assess vascular brain integrity should also be expanded. Measuring cortical blood flow or damage to the capillary system might, for instance, give insight about how vascular risk factors can be associated to amyloid burden and impact. These findings also stress the need for monitoring vascular risk factors in midlife as a strategy for Alzheimer’s disease prevention.
The Journal of Prevention of Alzheimer's Disease, pp 1-6; https://doi.org/10.14283/jpad.2015.37

Abstract:
BACKGROUND: Subjective memory complaints reflect patient-identified deficits in memory and have been linked to increased risk of future dementia in nondemented (including cognitively intact) older adults. OBJECTIVES: To assess the risk of incident dementia during follow-up for participants in the Prevention of Alzheimer’s Disease with Vitamin E and Selenium (PREADVISE) study who reported memory complaints at baseline. DESIGN: Double-blind, placebo controlled 2x2 randomized controlled trial that transformed into an observational cohort following discontinuation of supplementation in the SELECT parent trial. SETTING: PREADVISE participants were assessed at 130 local clinical study sites in the United States, Canada, and Puerto Rico during the controlled trial phase and were later followed by telephone from a centralized location during the observational phase. PARTICIPANTS: PREADVISE enrolled a total of 7,547 nondemented men over the age of 60; 4,271 consented to participation in the observational study. MEASUREMENTS: Participants were interviewed at baseline for memory complaints. The Memory Impairment Screen (MIS) was administered to each participant at the annual memory screening. Participants who failed the MIS also received a more detailed neurocognitive assessment: an expanded Consortium to Establish a Registry in Alzheimer’s Disease (CERADe) neuropsychological battery was used during the RCT, and the modified Telephone Interview for Cognitive Status (TICS-m) was used during the observational study. Participants who failed the second screen were asked to have a memory work-up with a local physician and to share their medical records with PREADVISE. Subgroups of men who did not fail the MIS were also asked to complete the CERADe battery and TICS-m for validation purposes. Additional measures collected include self-reported medical history, medication use, and the AD8 Dementia Screening Test. RESULTS: After controlling for important risk factors for dementia, Cox proportional hazards regression revealed that men who reported memory changes at baseline had an 80% increase in the hazard of incident dementia compared to men who reported no SMC. Men who reported memory problems at baseline had almost a 6-fold increase in the hazard of incident dementia compared to men who reported no memory complaint. CONCLUSIONS: Memory complaints in nondemented older men predicted future dementia. Men who reported that the changes in their memory were a problem were especially at risk, and the presence of common comorbidities like diabetes, sleep apnea, and history of head injury further exacerbated this risk.
R.A. Sperling, R.E. Amariglio, G.A. Marshall, D.M. Rentz
The Journal of Prevention of Alzheimer's Disease, pp 1-3; https://doi.org/10.14283/jpad.2015.56

, R. Bateman, K. Blennow, G. Frisoni, K. Johnson, R. Katz, J. Langbaum, D. Marson, R. Sperling, A. Wessels, et al.
The Journal of Prevention of Alzheimer's Disease, pp 1-8; https://doi.org/10.14283/jpad.2015.55

Abstract:
For Alzheimer’s disease treatment trials that focus on the pre-dementia stage of disease, outcome measures are needed that will enable assessment of disease progression in patients who are clinically normal. The EU/US CTAD Task Force, an international collaboration of investigators from industry, academia, non-profit foundations, and regulatory agencies, met in Philadelphia, Pennsylvania, USA, on November 19, 2014 to discuss existing and novel outcome assessments that may be useful in pre-dementia trials. Composite measures that assess changes in episodic memory, executive function, global cognition, and global function have recently been developed by a number of groups and appear to be sensitive at this stage. Functional measures that involve real-life complex tasks also appear to capture early subtle changes in pre-dementia subjects and have the advantage of representing clinically meaningful change. Patient reported outcomes and novel CSF and imaging biomarkers have also shown promise. More studies are needed to validate all of these tests in the pre-dementia population. Many of them have been incorporated as exploratory measures in ongoing or planned trials.
, S. Hendrix, N. Ayutyanont, D. A. Bennett, R.C. Shah, L.L. Barnes, F. Lopera, E.M. Reiman, P.N. Tariot
The Journal of Prevention of Alzheimer's Disease, pp 1-2; https://doi.org/10.14283/jpad.2015.46

, R. Eramudugolla, D.E. Hosking, N.T. Lautenschlager, R.A. Dixon
The Journal of Prevention of Alzheimer's Disease, pp 1-10; https://doi.org/10.14283/jpad.2015.75

Abstract:
Dementia risk reduction is a global health and fiscal priority given the current lack of effective treatments and the projected increased number of dementia cases due to population ageing. There are often gaps among academic research, clinical practice, and public policy. We present information on the evidence for dementia risk reduction and evaluate the progress required to formulate this evidence into clinical practice guidelines. This narrative review provides capsule summaries of current evidence for 25 risk and protective factors associated with AD and dementia according to domains including biomarkers, demographic, lifestyle, medical, and environment. We identify the factors for which evidence is strong and thereby especially useful for risk assessment with the goal of personalising recommendations for risk reduction. We also note gaps in knowledge, and discuss how the field may progress towards clinical practice guidelines for dementia risk reduction.
M. Soto, S. Abushakra, J. Cummings, J. Siffert, P. Robert, B. Vellas, C.G. Lyketsos
The Journal of Prevention of Alzheimer's Disease, pp 1-6; https://doi.org/10.14283/jpad.2015.77

Abstract:
Background: The management of neuropsychiatric symptoms (NPS) such as agitation and aggression is a major priority in caring for people with Alzheimer’s disease (AD). Agitation and aggression (A/A) are among the most disruptive symptoms, and given their impact, they are increasingly an important target for development of effective treatments. Considerable progress has been made in the last years with a growing number of randomized controlled trials (RCTs) of drugs for NPS. The limited benefits reported in some RCTs may be accounted for by the absence of a biological link of the tested molecule to NPS and also by key methodological issues. In recent RCTs of A/A, a great heterogeneity design was found. Designing trials for dementia populations with NPS presents many challenges, including identification of appropriate participants for such trials, engagement and compliance of patients and caregivers in the trials and the choice of optimal outcome measures to demonstrate treatment effectiveness. The EU/US -CTAD Task Force, an international collaboration of investigators from academia, industry, non-profit foundations, and regulatory agencies met in Philadelphia on November 19, 2014 to address some of these challenges. Despite potential heterogeneity in clinical manifestations and neurobiology, agitation and aggression seems to be accepted as an entity for drug development. The field appears to be reaching a consensus in using both agitation and aggression (or other NPS)-specific quantitative measures plus a global rating of change for agitation outcomes based on clinician judgment as the main outcomes.
, S. Lista, Z. Khachaturian, P. Aisen, , K. Herholz, C.R. Jack Jr, R. Sperling, J. Cummings, K. Blennow, et al.
The Journal of Prevention of Alzheimer's Disease, pp 1-22; https://doi.org/10.14283/jpad.2014.32

Abstract:
Alzheimer's disease (AD) is a slowly progressing non-linear dynamic brain disease in which pathophysiological abnormalities, detectable in vivo by biological markers, precede overt clinical symptoms by many years to decades. Use of these biomarkers for the detection of early and preclinical AD has become of central importance following publication of two international expert working group's revised criteria for the diagnosis of AD dementia, mild cognitive impairment (MCI) due to AD, prodromal AD and preclinical AD. As a consequence of matured research evidence six AD biomarkers are sufficiently validated and partly qualified to be incorporated into operationalized clinical diagnostic criteria and use in primary and secondary prevention trials. These biomarkers fall into two molecular categories: biomarkers of amyloid-beta (Aβ) deposition and plaque formation as well as of tau-protein related hyperphosphorylation and neurodegeneration. Three of the six gold-standard ("core feasible) biomarkers are neuroimaging measures and three are cerebrospinal fluid (CSF) analytes. CSF Aβ 1-42 (Aβ1-42), also expressed as Aβ1-42 : Aβ1- 40 ratio, T-tau, and P-tau Thr181 & Thr231 proteins have proven diagnostic accuracy and risk enhancement in prodromal MCI and AD dementia. Conversely, having all three biomarkers in the normal range rules out AD. Intermediate conditions require further patient follow-up. Magnetic resonance imaging (MRI) at increasing field strength and resolution allows detecting the evolution of distinct types of structural and functional abnormality pattern throughout early to late AD stages. Anatomical or volumetric MRI is the most widely used technique and provides local and global measures of atrophy. The revised diagnostic criteria for “prodromal AD” and "mild cognitive impairment due to AD" include hippocampal atrophy (as the fourth validated biomarker), which is considered an indicator of regional neuronal injury. Advanced image analysis techniques generate automatic and reproducible measures both in regions of interest, such as the hippocampus and in an exploratory fashion, observer and hypothesis-indedendent, throughout the entire brain. Evolving modalities such as diffusion-tensor imaging (DTI) and advanced tractography as well as resting-state functional MRI provide useful additionally useful measures indicating the degree of fiber tract and neural network disintegration (structural, effective and functional connectivity) that may substantially contribute to early detection and the mapping of progression. These modalities require further standardization and validation. The use of molecular in vivo amyloid imaging agents (the fifth validated biomarker), such as the Pittsburgh Compound-B and markers of neurodegeneration, such as fluoro-2-deoxy-D-glucose (FDG) (as the sixth validated biomarker) support the detection of early AD pathological processes and associated neurodegeneration. How to use, interpret, and disclose biomarker results drives the need for optimized standardization. Multimodal AD biomarkers do not evolve in an identical manner but rather in a sequential but temporally overlapping fashion. Models of the temporal evolution of AD biomarkers can take the form of plots of biomarker severity (degree of abnormality) versus time. AD biomarkers can be combined to increase accuracy or risk. A list of genetic risk factors is increasingly included in secondary prevention trials to stratify and select individuals at genetic risk of AD. Although most of these biomarker candidates are not yet qualified and approved by regulatory authorities for their intended use in drug trials, they are nonetheless applied in ongoing clinical studies for the following functions: (i) inclusion/exclusion criteria, (ii) patient stratification, (iii) evaluation of treatment effect, (iv) drug target engagement, and (v) safety. Moreover, novel promising hypothesis-driven, as well as exploratory biochemical, genetic, electrophysiological, and neuroimaging markers for use in clinical trials are being developed. The current state-of-the-art and future perspectives on both biological and neuroimaging derived biomarker discovery and development as well as the intended application in prevention trials is outlined in the present publication.
K.T. Saunders, J.B. Langbaum, C.J. Holt, W. Chen, N. High, C. Langlois, M. Sabbagh, P.N. Tariot
The Journal of Prevention of Alzheimer's Disease, pp 1-6; https://doi.org/10.14283/jpad.2014.1

Abstract:
Background:The Arizona Alzheimer’s Consortium (AAC) created the Arizona Alzheimer’s Registry, a screening and referral process for people interested in participating in Alzheimer’s disease related research. The goals of the Registry were to increase awareness of Alzheimer's disease research and accelerate enrollment into AAC research studies. Methods: Participation was by open invitation to adults 18 and older. Those interested provided consent and completed a written questionnaire. A subset of Registrants underwent an initial telephone cognitive assessment. Referral to AAC sites was based on medical history, telephone cognitive assessment, and research interests. Results: A total of 1257 people consented and 1182 underwent an initial cognitive screening. Earned media (38.7%) was the most effective recruitment strategy. Participants had a mean age of 68.1 (SD 10.6), 97% were Caucasian, had 15.2 (SD 2.7) mean years of education, and 60% were female. 30% reported a family history of dementia and 70% normal cognition. Inter-rater agreement between self-reported memory status and the initial telephone cognitive assessment had a kappa of 0.31-0.43. 301 were referred to AAC sites. Conclusion: IThe Registry created an infrastructure and process to screen and refer a high volume of eager Registrants. These methods were found to be effective at prescreening individuals for studies, which facilitated AAC research recruitment. The established infrastructure and experiences gained from the Registry have served as the prototype for the web-based Alzheimer’s Prevention Registry, a national registry focusing on Alzheimer's disease prevention research.
A.S. Atkins, I. Stroescu, N.B. Spagnola, V.G. Davis, T.D. Patterson, M. Narasimhan, P.D. Harvey,
The Journal of Prevention of Alzheimer's Disease, pp 1-7; https://doi.org/10.14283/jpad.2015.61

Abstract:
Clinical trials for primary prevention and early intervention in preclinical AD require measures of functional capacity with improved sensitivity to deficits in healthier, non-demented individuals. To this end, the Virtual Reality Functional Capacity Assessment Tool (VRFCAT) was developed as a direct performance-based assessment of functional capacity that is sensitive to changes in function across multiple populations. Using a realistic virtual reality environment, the VRFCAT assesses a subject’s ability to complete instrumental activities associated with a shopping trip. The present investigation represents an initial evaluation of the VRFCAT as a potential co-primary measure of functional capacity in healthy aging and preclinical MCI/AD by examining test-retest reliability and associations with cognitive performance in healthy young and older adults. The VRFCAT was compared and contrasted with the UPSA-2-VIM, a traditional performance-based assessment utilizing physical props. Results demonstrated strong age-related differences in performance on each VRFCAT outcome measure, including total completion time, total errors, and total forced progressions. VRFCAT performance showed strong correlations with cognitive performance across both age groups. VRFCAT Total Time demonstrated good test-retest reliability (ICC=.80 in young adults; ICC=.64 in older adults) and insignificant practice effects, indicating the measure is suitable for repeated testing in healthy populations. Taken together, these results provide preliminary support for the VRFCAT as a potential measure of functionally relevant change in primary prevention and preclinical AD/MCI trials.
, M. Dekhtyar, J.M. Bruno, K. Jethwani, R.E. Amariglio, K.A. Johnson, R.A. Sperling, D.M. Rentz
The Journal of Prevention of Alzheimer's Disease, pp 1-12; https://doi.org/10.14283/jpad.2015.72

Abstract:
Background: Impairment in activities of daily living is a major burden for Alzheimer’s disease dementia patients and caregivers. Multiple subjective scales and a few performance-based instruments have been validated and proven to be reliable in measuring instrumental activities of daily living in Alzheimer’s disease dementia but less so in amnestic mild cognitive impairment and preclinical Alzheimer’s disease. Objective: To validate the Harvard Automated Phone Task, a new performance-based activities of daily living test for early Alzheimer’s disease, which assesses high level tasks that challenge seniors in daily life. Design: In a cross-sectional study, the Harvard Automated Phone Task was associated with demographics and cognitive measures through univariate and multivariate analyses; ability to discriminate across diagnostic groups was assessed; test-retest reliability with the same and alternate versions was assessed in a subset of participants; and the relationship with regional cortical thickness was assessed in a subset of participants. Setting: Academic clinical research center. Participants: One hundred and eighty two participants were recruited from the community (127 clinically normal elderly and 45 young normal participants) and memory disorders clinics at Brigham and Women’s Hospital and Massachusetts General Hospital (10 participants with mild cognitive impairment). Measurements: As part of the Harvard Automated Phone Task, participants navigated an interactive voice response system to refill a prescription (APT-Script), select a new primary care physician (APT-PCP), and make a bank account transfer and payment (APT-Bank). The 3 tasks were scored based on time, errors, and repetitions from which composite z-scores were derived, as well as a separate report of correct completion of the task. Results: We found that the Harvard Automated Phone Task discriminated well between diagnostic groups (APT-Script: p=0.002; APT-PCP: p<0.001; APT-Bank: p=0.02), had an incremental level of difficulty, and had excellent test-retest reliability (Cronbach’s α values of 0.81 to 0.87). Within the clinically normal elderly, there were significant associations in multivariate models between performance on the Harvard Automated Phone Task and executive function (APT-PCP: p<0.001), processing speed (APT-Script: p=0.005), and regional cortical atrophy (APT-PCP: p=0.001; no significant association with APT-Script) independent of hearing acuity, motor speed, age, race, education, and premorbid intelligence. Conclusions: Our initial experience with the Harvard Automated Phone Task, which consists of ecologically valid, easily-administered measures of daily activities, suggests that these tasks could be useful for screening and tracking the earliest functional alterations in preclinical and early prodromal AD.
, N. Ellison, S. Stanworth, L. Tierney, F. Mattner, W. Schmidt, B. Dubois, A. Schneeberger
The Journal of Prevention of Alzheimer's Disease, pp 1-12; https://doi.org/10.14283/jpad.2015.67

Abstract:
BACKGROUND: Optimized scales and composite outcomes have been proposed as a way to more accurately measure Alzheimer’s disease related decline. AFFITOPE® AD02, is an amyloid-beta (Aβ)-targeting vaccine to elicit anti-Aβ antibodies. IMM-AD04, commonly known as Alum, originally designated as a control agent, appeared to have disease-modifying activity in a multicenter, parallel group phase II study in early AD patients. OBJECTIVES: To develop adapted outcomes for cognition, function and a composite scale with improved sensitivity to decline and treatment effects in early AD (mild plus prodromal AD) based on historical data and to assess these adapted outcomes in this phase II study. DESIGN: Data from public datasets was analyzed using a partial least squares model in order to identify an optimally weighted cognitive outcome, Adapted ADAS-cog, and an optimally weighted ADL outcome, Adapted ADCS-ADL which were prospectively defined as co-primary endpoints for the study and were also combined into a composite scale. Data from 162 patients in the placebo groups of ADCS studies and 156 mild patients in the ADNI I study were pooled for this analysis. The Adapted ADAS-cog scale considered 13 ADAS-cog items as well as several Neuropsychological test items and CogState items, the Adapted ADCS-ADL considered all ADCS-ADL items. After the pre-specified analyses were complete, additional adapted and composite scales were investigated in a post-hoc manner. Evaluation of the adapted and composite scales was performed on Phase II trial data for AFFITOPE® AD02 (AFF006, Clinical Trial Identifier: NCT01117818) and historic data in early AD. Least square means, standard deviations, and least squares mean to standard deviation ratios were compared among adapted and composite scales and traditional scales for the 5 treatment groups in the phase II study and overall for the historic data. Treatment effect sizes and p-values were also compared for the phase II study. RESULTS: Cognitive items that were selected for the adapted cognitive scale (aADAS-cog) and had the highest weights were Word Recall, Word Recognition, and Orientation. Delayed Word Recall and Digit Cancellation were among the items excluded due to lack of improved sensitivity to decline. Highly weighted ADL items included in the adapted functional scale (aADCS-ADL) were using the telephone, traveling, preparing a meal/snack, selecting clothing, shopping and using appliances. Excluded items were primarily basic ADLs such as eating, walking, toileting and bathing. Comparisons between traditional scales and primary outcome adapted scales show improved sensitivity to group differences with the adapted scales in the phase II trial. Most of the improvement in the sensitivity of the aADAS-cog and the aADCS-ADL is due to a larger treatment difference observed rather than the improved sensitivity to decline in the comparison groups. CONCLUSION: To our knowledge, this is the first study to prospectively use optimized scales as primary endpoints and to demonstrate the superior power of optimized scales and composites in early disease. Although it is possible that the treatment difference between randomized groups is due to a factor other than the treatment itself, for instance baseline imbalance, the improved power to detect these differences still argues in favor of the adapted scales. The issue of oversensitivity to detect treatment effects is controlled by selection of the alpha level for significance, and in our case will happen less than 5% of the time. Clinical relevance of the treatment difference should be assessed separately from statistical significance, and in this phase II study, is supported by significant or similar sizes of effect on function, behaviour and quality of life outcomes, which are important to patients and caregivers.
G.E. Crichton, M.F. Elias, A. Davey, A. Alkerwi, G.A. Dore
The Journal of Prevention of Alzheimer's Disease, pp 1-9; https://doi.org/10.14283/jpad.2015.39

Abstract:
Objectives: Few studies have examined whether cognitive function predicts dietary intake. The majority of research has focused on how diet can influence cognitive performance or risk for cognitive impairment in later life. The aim of this study was to examine prospective relationships between cognitive performance and dietary intake in participants of the Maine-Syracuse Longitudinal Study. Design: A prospective study with neuropsychological testing at baseline and nutritional assessments measured a mean of 18 years later. Setting: Community-dwelling individuals residing in central New York state. Participants: 333 participants free of dementia and stroke. Measurements: The Wechsler Adult Intelligence Scale (WAIS) was assessed at baseline and dietary intake was measured using the Nutrition and Health Questionnaire. Results: Higher WAIS Scores at baseline were prospectively associated with higher intakes of vegetables, meats, nuts and legumes, and fish, but inversely associated with consumption of total grains and carbonated soft drinks. After adjustment for sample selection, socioeconomic indicators, lifestyle factors (smoking and physical activity), and cardiovascular risk factors, the relations between higher cognitive performance and greater consumption of vegetables, meat, and fish, and lower consumption of grains remained significant. Conclusion: These data suggest that cognition early in life may influence dietary choices later in life.
, J.A. Blumenthal
The Journal of Prevention of Alzheimer's Disease, pp 1-12; https://doi.org/10.14283/jpad.2015.71

Abstract:
Cognitive decline is an increasingly important public health problem, with more than 100 million adults worldwide projected to develop dementia by 2050. Accordingly, there has been an increased interest in preventive strategies that diminish this risk. It has been recognized that lifestyle factors including dietary patterns, may be important in the prevention of cognitive decline and dementia in later life. Several dietary components have been examined, including antioxidants, fatty acids, and B vitamins. In addition, whole dietary eating plans, including the Mediterranean diet (MeDi), and the Dietary Approaches to Stop Hypertension (DASH) diet, with and without weight loss, have become areas of increasing interest. Although prospective epidemiological studies have observed that antioxidants, fatty acids, and B vitamins are associated with better cognitive functioning, randomized clinical trials have generally failed to confirm the value of any specific dietary component in improving neurocognition. Several randomized trials have examined the impact of changing ‘whole’ diets on cognitive outcomes. The MeDi and DASH diets offer promising preliminary results, but data are limited and more research in this area is needed.
, M. Dekhtyar, J. Sherman, S. Burnham, D. Blacker, S.L. Aghjayan, K.V. Papp, R.E. Amariglio, A. Schembri, T. Chenhall, et al.
The Journal of Prevention of Alzheimer's Disease, pp 1-5; https://doi.org/10.14283/jpad.2015.78

Abstract:
Background: Technological advances now make it feasible to administer cognitive assessments at-home on mobile and touch-screen devices such as an iPad or tablet computer. Validation of these techniques is necessary to assess their utility in clinical trials. Objectives: We used a Computerized Cognitive Composite for Preclinical Alzheimer’s Disease (C3-PAD) developed for iPad 1) to determine the feasibility of performing the C3-PAD at home by older individuals without the presence of a trained psychometrician; 2) to explore the reliability of in-clinic compared to at-home C3-PAD performance and 3) to examine the comparability of C3-PAD performance to standardized neuropsychological tests. Design, Setting, Participants: Forty-nine cognitively normal older individuals (mean age, 71.46±7.7 years; 20% non-Caucasian) were recruited from research centers at the Massachusetts General Hospital and Brigham and Women’s Hospital. Participants made two in-clinic visits one-week apart and took five 30-minute alternate versions of the C3-PAD at-home measuring episodic memory, reaction time and working memory. Measurements: A reliability analysis explored equivalence of the six alternate C3-PAD test versions. A feasibility assessment calculated the percentage of individuals who completed all at-home tests correctly, in contrast to incomplete assessments. Correlational analyses examined the association between C3-PAD-clinic compared to C3-PAD-home assessments and between C3-PAD performance and standardized paper and pencil tests. Results: Excellent reliability was observed among the 6 C3-PAD alternate versions (Cronbach alpha coefficient=0.93). A total of 28 of 49 participants completed all at-home sessions correctly and 48 of 49 completed four out of five correctly. There were no significant differences in participant age, sex or education between complete and incomplete at-home assessments. A single in-clinic C3-PAD assessment and the at-home C3-PAD assessments were highly associated with each other (r2=0.508, p<0.0001), suggesting that at-home tests provide reliable data as in-clinic assessments. There was also a moderate association between the at-home C3-PAD assessments and the in-clinic standardized paper and pencil tests covering similar cognitive domains (r2= 0.168, p< 0.003). Conclusions: Reliable and valid cognitive data can be obtained from the C3-PAD assessments in the home environment. With initial in-clinic training, a high percentage of older individuals completed at-home assessments correctly. At-home cognitive testing shows promise for inclusion into clinical trial designs.
, E.R. Siemers, P. Yu, S.W. Andersen, K.C. Holdridge, J.R. Sims, K. Sundell, Y. Stern, D.M. Rentz, B. Dubois, et al.
The Journal of Prevention of Alzheimer's Disease, pp 1-15; https://doi.org/10.14283/jpad.2015.82

Abstract:
It is generally recognized that more sensitive instruments for the earliest stages of Alzheimer’s disease (AD) are needed. The integrated Alzheimer’s Disease Rating Scale (iADRS) combines scores from 2 widely accepted measures, the Alzheimer’s Disease Assessment Scale-Cognitive subscale (ADAS-Cog) and the Alzheimer’s Disease Cooperative Study – instrumental Activities of Daily Living (ADCS-iADL). Disease progression and treatment differences as measured by the iADRS were analyzed using data from solanezumab EXPEDITION, EXPEDITION2, and EXPEDITION-EXT Studies; semagacestat IDENTITY Study; and donepezil ADCS – mild cognitive impairment (ADCS-MCI) Study. Psychometric properties of the iADRS were established through principal component analysis (PCA) and estimation of contributions of subscores and individual item scores to the iADRS total score. The iADRS performed better than most composites and scales in detecting disease progression and comparably or better than individual scales in detecting treatment differences. PCA demonstrated the iADRS can be divided into two principal components primarily representing cognitive items and instrumental ADLs. Dynamic ranges of the subscales were similar across all studies, reflecting approximately equal contributions from both subscales to the iADRS total score. In item analyses, every item contributed to the total score, with varying strength of contributions by item and across data sets. The iADRS demonstrated acceptable psychometric properties and was effective in capturing disease progression from MCI through moderate AD and treatment effects across the early disease spectrum. These findings suggest the iADRS can be used in studies of mixed populations, ensuring sensitivity to treatment effects as subjects progress during studies of putative disease-modifying agents.
, E.L. Abner, G.A. Jicha, P.T. Nelson, C.D. Smith, L.J. Van Eldik, W. Lou, D.W. Fardo, G.E. Cooper, F.A. Schmitt
The Journal of Prevention of Alzheimer's Disease, pp 1-7; https://doi.org/10.14283/jpad.2015.74

Abstract:
Background: Subjective memory complaints are common in aged persons, indicating an increased, but incompletely understood, risk for dementia. Objective: To compare cognitive trajectories and autopsy results of individuals with subjective complaints after stratifying by whether a subsequent clinical dementia occurred. Design: Observational study. Setting: University of Kentucky cohort with yearly longitudinal assessments and eventual autopsies Participants: Among 516 patients who were cognitively intact and depression-free at enrollment, 296 declared a memory complaint during follow-up. Among those who came to autopsy, 118 died but never developed dementia, while 36 died following dementia diagnosis. Measurements: Cognitive domain trajectories were compared using linear mixed models adjusted for age, gender, years of education and APOE status. Neuropathological findings were compared cross-sectionally after adjustment for age at death. Results: While the groups had comparable cognitive test scores at enrollment and the time of the first declaration of a complaint, the group with subsequent dementia development had steeper slopes of decline in episodic memory and naming but not fluency or sequencing. Autopsies showed the dementia group had more severe Alzheimer pathology and a higher proportion of subjects with hippocampal sclerosis of aging and arteriolosclerosis, whereas the non-demented group had a higher proportion expressing primary age related tauopathy (PART). Conclusions: While memory complaints are common among the elderly, not all individuals progress to dementia. This study indicates that biomarkers are needed to predict whether a complaint will lead to dementia if this is used as enrollment criteria in future clinical trials.
N. Yamane, A. Ikeda, K. Tomooka, I. Saito, K. Maruyama, E. Eguchi, K. Suyama, A. Fujii, T. Shiba, K. Tanaka, et al.
The Journal of Prevention of Alzheimer's Disease pp 1-6; https://doi.org/10.14283/jpad.2022.51

Abstract:
There is growing interest in examining objective markers for early identification and behavioral intervention to prevent dementia and mild cognitive impairment in clinical and community settings.
, L. Van Neste, C. Fowler, C. L. Masters, J. Fripp, J. D. Doecke, C. Xiong, D. Uberti, P. Kinnon
The Journal of Prevention of Alzheimer's Disease pp 1-11; https://doi.org/10.14283/jpad.2022.52

Abstract:
Ongoing research seeks to identify blood-based biomarkers able to predict onset and progression of Alzheimer’s disease (AD).
, P. Aisen, M. C. Carillo, M. Detke, J. D. Grill, O. C. Okonkwo, M. Rivera-Mindt, M. Sabbagh, B. Vellas, M. Weiner, et al.
The Journal of Prevention of Alzheimer's Disease pp 1-5; https://doi.org/10.14283/jpad.2022.50

Abstract:
As the last opportunity to assess treatment effect modification in a controlled setting prior to formal approval, clinical trials are a critical tool for understanding the safety and efficacy of new treatments in diverse populations. Recruitment of diverse participants in Alzheimer’s Disease (AD) clinical trials are therefore essential to increase the generalizability of study results, with diversity broadly described to be representative and inclusive. This representation of study participants is equally critical in longitudinal cohort (observational) studies, which will be key to understanding disease disparities and are often used to design adequately powered AD clinical trials. New and innovative recruitment initiatives and enhanced infrastructure facilitate increased participant diversity in AD clinical studies.
A. Tam, C. Laurent, S. Gauthier,
The Journal of Prevention of Alzheimer's Disease pp 1-10; https://doi.org/10.14283/jpad.2022.49

Abstract:
A key issue to Alzheimer’s disease clinical trial failures is poor participant selection. Participants have heterogeneous cognitive trajectories and many do not decline during trials, which reduces a study’s power to detect treatment effects. Trials need enrichment strategies to enroll individuals who are more likely to decline.
C. G. Lyketsos, S. B. Roberts, , A. Quina, G. Moon, I. Kremer, P. Tariot, H. Fillit, D. E. Bovenkamp, P. P. Zandi, et al.
The Journal of Prevention of Alzheimer's Disease pp 1-5; https://doi.org/10.14283/jpad.2022.47

Abstract:
Improving the prevention, detection, and treatment of Alzheimer’s disease and Alzheimer’s disease related dementias (AD/ADRD) across racial, ethnic, and other diverse populations is a national priority. To this end, this paper proposes the development of the Standard Health Record for Dementia (SHRD, pronounced “shared”) for collecting and sharing AD/ADRD real-world data (RWD). SHRD would replace the current unstandardized, fragmented, or missing state of key RWD with an open source, consensus-based, and interoperable common data standard. This paper describes how SHRD could leverage the best practices of the Minimal Common Oncology Data Elements (mCODE™) initiative to advance prevention, detection, and treatment; gain adoption by clinicians and electronic health record (EHR) vendors; and establish sustainable business and governance models. It describes a range of potential use cases to advance equity, including strengthening public health surveillance by facilitating AD/ADRD registry reporting; improving case detection and staging; and diversifying participation in clinical trials.
Q. Wang, F. Gao, L. Dai, J. Zhang, D. Bi,
The Journal of Prevention of Alzheimer's Disease pp 1-10; https://doi.org/10.14283/jpad.2022.46

Abstract:
Based on the background of research investigating brain aging and neurodegenerative diseases in China, the present review addresses Alzheimer’s disease (AD), one of the most common types of neurodegenerative diseases, clinical research progress, and prospects for future development in China.
, J. Cummings, S. Knox, M. Potashman, J. Harrison
The Journal of Prevention of Alzheimer's Disease pp 1-16; https://doi.org/10.14283/jpad.2022.41

Abstract:
As the focus of Alzheimer’s disease (AD) therapeutic development shifts to the early stages of the disease, the clinical endpoints used in drug trials, and how these might translate into clinical practice, are of increasing importance. The clinical meaningfulness of trial outcome measures is often unclear, with a lack of conclusive evidence as to how these measures correlate to changes in disease progression and treatment response. Clarifying this would benefit all, including patients, care partners, primary care providers, regulators, and payers, and would enhance our understanding of the relationship between clinical trial endpoints and assessments used in everyday practice. At present, there is a wide range of assessment tools used in clinical trials for AD and substantial variability in measures selected as endpoints across these trials. The aim of this review is to summarize the most commonly used assessment tools for early stages of AD, describe their use in clinical trials and clinical practice, and discuss what might constitute clinically meaningful change in these measures in relation to disease progression and treatment response.
N. Saif, H. Hristov, K. Akiyoshi, K. Niotis, I. E. Ariza, N. Malviya, P. Lee, J. Melendez, G. Sadek, K. Hackett, et al.
The Journal of Prevention of Alzheimer's Disease pp 1-12; https://doi.org/10.14283/jpad.2022.44

Abstract:
The Comparative Effectiveness Dementia & Alzheimer’s Registry (CEDAR) trial demonstrated that individualized, multi-domain interventions improved cognition and reduced the risk of Alzheimer’s disease (AD). As biological sex is a significant risk factor for AD, it is essential to explore the differential effectiveness of targeted clinical interventions in women vs. men.
Q. Behfar, A. Ramirez Zuniga,
The Journal of Prevention of Alzheimer's Disease pp 1-9; https://doi.org/10.14283/jpad.2022.42

Abstract:
The underlying processes occurring in aging are complex, involving numerous biological changes that result in chronic cellular stress and sterile inflammation. One of the main hallmarks of aging is senescence. While originally the term senescence was defined in the field of oncology further research has established that also microglia, astrocytes and neurons become senescent. Since age is the main risk factor for neurodegenerative diseases, it is reasonable to argue that cellular senescence might play a major role in Alzheimer’s disease. Specific cellular changes seen during Alzheimer’s disease are similar to those observed during senescence across all resident brain cell types. Furthermore, increased levels of senescence-associated secretory phenotype proteins such as IL-6, IGFBP, TGF-β and MMP-10 have been found in both CSF and plasma samples from Alzheimer’s disease patients. In addition, genome-wide association studies have identified that individuals with Alzheimer’s disease carry a high burden of genetic risk variants in genes known to be involved in senescence, including ADAMIO, ADAMTS4, and BIN1. Thus, cellular senescence is emerging as a potential underlying disease process operating in Alzheimer’s disease. This has also attracted more attention to exploiting cellular senescence as a therapeutic target. Several senolytic compounds with the capability to eliminate senescent cells have been examined in vivo and in vitro with notable results, suggesting they may provide a novel therapeutic avenue. Here, we reviewed the current knowledge of cellular senescence and discussed the evidence of senescence in various brain cell types and its putative role in inflammaging and neurodegenerative processes.
, D. Sánchez, G. Ortega, M. Buendía, J. Papasey, S. Y. Jimeno, F. P. Badia, M. E. Palacio, C. Abdelnour, F. Ramírez-Toraño, et al.
The Journal of Prevention of Alzheimer's Disease pp 1-10; https://doi.org/10.14283/jpad.2022.38

Abstract:
There are currently no drug therapies modifying the natural history of patients suffering Alzheimer’s disease (AD). Most recent clinical trials in the field include only subjects in early stage of the disease, while patients with advanced AD are usually not represented.
L. Gao, W. Ge, C. Peng, J. Guo, Ning Chen, L. He
The Journal of Prevention of Alzheimer's Disease pp 1-9; https://doi.org/10.14283/jpad.2022.39

Abstract:
Despite reports on neuroprotective effects of dietary theobromine intake, whether dietary theobromine has beneficial effects on cognitive function is unclear.
Lihua Gu, H. Xu, F. Qian
The Journal of Prevention of Alzheimer's Disease pp 1-15; https://doi.org/10.14283/jpad.2022.40

Abstract:
Previous meta-analyses did not explore the immediate and long-term effect of non-invasive brain stimulation (NIBS) on different cognitive domains in Alzheimer’s disease (AD). The meta-analysis aimed to assess the therapy effect of repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) on different cognitive domains in AD in randomized controlled trials (RCTs).
, G. D. Rabinovici, A. Atri, P. Aisen, L. G. Apostolova, S. Hendrix, M. Sabbagh, D. Selkoe, M. Weiner, S. Salloway
The Journal of Prevention of Alzheimer's Disease pp 1-10; https://doi.org/10.14283/jpad.2022.34

Abstract:
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.
Ronald C. Petersen
The Journal of Prevention of Alzheimer's Disease pp 1-2; https://doi.org/10.14283/jpad.2022.35

M. Anderson, N. Sathe, C. Polacek, J. Vawter, T. Fritz, M. Mann, P. Hernandez, M.C. Nguyen, J. Thompson, J. Penderville, et al.
The Journal of Prevention of Alzheimer's Disease; https://doi.org/10.14283/jpad.2022.32

, J. Inker, J. Richardson, F. Zanjani
The Journal of Prevention of Alzheimer's Disease pp 1-9; https://doi.org/10.14283/jpad.2022.33

Abstract:
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.
, L. Manning, D. Kirn, H. Klein, O. Hampton, O. Burke Jr., R. Buckley, D. Rentz, R. Sperling, G. A. Marshall, et al.
The Journal of Prevention of Alzheimer's Disease pp 1-6; https://doi.org/10.14283/jpad.2022.31

Abstract:
With the increasing focus on prevention of Alzheimer’s disease, there is need for characterization of preclinical populations. Local participant registries offer an opportunity to facilitate research engagement via remote data collection, inform recruitment, and characterize preclinical samples, including individuals with subjective cognitive decline.
, P.S. Aisen, F. Barkhof, S. Chalkias, T. Chen, S. Cohen, G. Dent, O. Hansson, K. Harrison, C. von Hehn, et al.
The Journal of Prevention of Alzheimer's Disease pp 1-14; https://doi.org/10.14283/jpad.2022.30

Abstract:
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.
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