Ahead of print articles
EFFECTS OF A SIX-MONTH MULTI-INGREDIENT NUTRITION SUPPLEMENT INTERVENTION OF OMEGA-3 POLYUNSATURATED FATTY ACIDS, VITAMIN D, RESVERATROL, AND WHEY PROTEIN ON COGNITIVE FUNCTION IN OLDER ADULTS: A RANDOMISED, DOUBLE-BLIND, CONTROLLED TRIAL
C. Moran, A. Scotto di Palumbo, J. Bramham, A. Moran, B. Rooney, G. De Vito, B. Egan
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Objectives: To investigate the impact of a six-month multi-ingredient nutrition supplement intervention (Smartfish®), containing omega-3 polyunsaturated fatty acids (PUFAs), vitamin D, resveratrol, and whey protein, on cognitive function in Irish older adults.
Design: Double-blind, randomised controlled trial (ClinicalTrials.gov: NCT02001831). A quantitative, mixed-model design was employed in which the dependent variable (cognitive function) was analysed with a between-subjects factor of group (placebo, intervention) and within-subjects factor of testing occasion (baseline, three-months, six-months).
Setting: Community-based intervention including assessments conducted at University College Dublin, Ireland.
Participants: Thirty-seven community-dwelling older adults (68-83 years; mean (x̄)= 75.14 years; standard deviation (SD)= 3.64; 18 males) with normal cognitive function (>24 on the Mini Mental State Examination) were assigned to the placebo (n= 17) or intervention (n= 20) via a block randomisation procedure.
Intervention: Daily consumption for six-months of a 200mL liquid juice intervention comprising 3000mg omega-3 PUFAs [1500mg docosahexaenoic acid (DHA) and 1500mg eicosapentaenoic acid (EPA)], 10μg vitamin D3, 150mg resveratrol and 8g whey protein isolate. The placebo contained 200mL juice only.
Measurements: A standardised cognitive assessment battery was conducted at baseline and follow-ups. Individual test scores were z-transformed to generate composite scores grouped into cognitive domains: executive function, memory, attention and sensorimotor speed. Motor imagery accuracy and subjective awareness of cognitive failures variables were computed from raw scores.
Results: A hierarchical statistical approach was used to analyse the data; first, by examining overall cognitive function, then by domain, and then by individual test scores. Using mixed between-within subjects, analyses of variance (ANOVAs), no significant differences in overall cognitive function or composite cognitive domains were observed between groups over time. The only significant interaction was for Stroop Color-Word Time (p< 0.05). The intervention group demonstrated reduced task completion time at three- and six-month follow-ups, indicating enhanced performance.
Conclusion: The present nutrition intervention encompassed a multi-ingredient approach targeted towards improving cognitive function, but overall had only a limited beneficial impact in the older adult sample investigated. Future investigations should seek to establish any potential clinical applications of such targeted interventions with longer durations of supplementation, or in populations with defined cognitive deficits.
C. Moran ; A. Scotto di Palumbo ; J. Bramham ; A. Moran ; B. Rooney ; G. De Vito ; B. Egan (2018): Effects of a Six-Month Multi-Ingredient Nutrition Supplement Intervention of Omega-3 Polyunsaturated Fatty Acids, vitamin D, Resveratrol, and Whey Protein on Cognitive Function in Older Adults: A Randomised, Double-Blind, Controlled Trial. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2018.11
THE ROLE OF ADVANCED PRACTICE NURSES IN ALZHEIMER’S DISEASE PREVENTION
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B. Fougère (2018): The Role of Advanced Practice Nurses in Alzheimer’s Disease Prevention. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2018.8
FATTY ACIDS AND ALZHEIMER’S DISEASE: EVIDENCE ON COGNITION AND CORTICAL ?-AMYLOID FROM SECONDARY ANALYSES OF THE MULTIDOMAIN ALZHEIMER PREVENTIVE TRIAL
C. Hooper, B. Vellas
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C. Hooper ; B. Vellas (2018): Fatty acids and Alzheimer’s disease: evidence on cognition and cortical β-amyloid from secondary analyses of the Multidomain Alzheimer Preventive Trial. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2018.7
CORRELATION OF CSF- AND MRI-BIOMARKERS AND PROGRESSION OF COGNITIVE DECLINE IN AN OPEN LABEL MCI TRIAL
L.K. Joachim, L. Frölich, E. Rüther, J. Wiltfang, W. Maier, J. Kornhuber, C. Bauer, I. Heuser, O. Peters
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Background: In several randomized controlled trials (RCT) acetylcholinesterase-inhibitors (AChE-I) were tested in patients with mild cognitive impairment (MCI) but were ineffective in delaying disease progression as determined by neuropsychological testing only. Here we present data from an open label observational extension of a multicenter RCT in order to assess if biomarkers are providing useful additional information about a drug’s efficacy. We followed 83 amnestic MCI patients and performed correlational analyses of Aβ 1-42 and total-Tau in the cerebrospinal fluid (CSF), hippocampal and amygdala volume at baseline, the total duration of blinded and open label AChE-I treatment and the outcome 24 months after inclusion into the RCT. Twelve out of 83 amnestic MCI (14%) had progressed to Alzheimer’s disease (AD). Overall, worsening and disease progression as measured by the Alzheimer’s Disease Assessment Scale - cognitive subscale (ADAS-cog), Alzheimer’s Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) and Clinical Dementia Rating (CDR) did not correlate with the duration of AChE-I treatment. However, a specific multidimensional biomarker profile at baseline indicated more reliably than cognitive testing alone progression to AD. We conclude that pharmacological RCTs testing symptomatic treatment effects in MCI should include biomarker assessment.
L.K. Joachim ; L. Frölich ; E. Rüther ; J. Wiltfang ; W. Maier ; J. Kornhuber ; C. Bauer ; I. Heuser ; O. Peters (2018): Correlation of CSF- and MRI-Biomarkers and Progression of Cognitive Decline in an Open Label MCI Trial. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2018.5
AURAPTENE IN THE PEELS OF CITRUS KAWACHIENSIS (KAWACHIBANKAN) CONTRIBUTES TO THE PRESERVATION OF COGNITIVE FUNCTION: A RANDOMIZED, PLACEBO-CONTROLLED, DOUBLE-BLIND STUDY IN HEALTHY VOLUNTEERS
M. Igase, Y. Okada, M. Ochi, K. Igase, H. Ochi, S. Okuyama, Y. Furukawa, Y. Ohyagi
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OBJECTIVES: Dementia, which is characterized by a progressive decline in cognitive function, is a major concern in aging societies. Although a number of treatments have been approved, an effective therapy to prevent the disorder is lacking. A supplement that improves cognitive function would benefit patients. The aim of this study was to assess whether auraptene, a citrus coumarin, has a protective effect on cognitive decline.
DESIGN: A randomized, placebo-controlled, double-blind study
SETTING: Outpatient medical check-up program for cognitive disorders
PARTICIPANTS: 84 adult volunteers (they are cognitively normal) met inclusion and exclusion criteria to participate.
INTERVENTION: 42 participants received auraptene enriched (containing 6.0 mg/day of auraptene) test juice, and another participants received placebo juice.
MEASUREMENTS: 1) Mild Cognitive Impairment (MCI) Screen using the 10-word immediate recall test. 2) The Mini-Mental State Examination (MMSE). Cognitive assessment ware carried out baseline and at 24 weeks.
RESULTS: Auraptene enriched test juice did not improve cognitive function after 24 weeks compared with baseline data. However, there was a significant difference in the percentage change in cognitive function between the test and placebo orange juice groups (6.3 ± 18.9 vs. −2.4 ± 14.8, P < 0.05). Multiple regression analysis demonstrated a significant independent relationship between the percentage change in the 10-word immediate recall test score and test juice consumption including baseline 10-word immediate recall test score in all subjects.
CONCLUSION: This is the first study to assess the effectiveness of auraptene in the prevention of cognitive decline. Our results suggest that auraptene is a safe supplement for the prevention of cognitive decline.
M. Igase ; Y. Okada ; M. Ochi ; K. Igase ; H. Ochi ; S. Okuyama ; Y. Furukawa ; Y. Ohyagi (2017): Auraptene in the Peels of Citrus Kawachiensis (Kawachibankan) Contributes to the Preservation of Cognitive Function: A Randomized, Placebo-Controlled, Double-Blind Study in Healthy Volunteers. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2017.47
JPAD Volume 5, N°02 - 2018
PREVENTION OF ALZHEIMER’S DISEASE IN CHINESE POPULATIONS: STATUS, CHALLENGES AND DIRECTIONS
L. Feng, J. Li, J.-T. Yu, C. Zhang, B. Yang, B. Vellas, C. Li
J Prev Alz Dis 2018;5(2):90-94Show summaryHide summary
L. Feng ; J. Li ; J.-T. Yu ; C. Zhang ; B. Yang ; B. Vellas ; C. Li (2018): Prevention of Alzheimer’s Disease in Chinese Populations: Status, Challenges and Directions. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2018.14
DIABETES MELLITUS AND COGNITIVE DECLINE – PREVENTION SHOULD NOT BE DELAYED!
A.J. Sinclair, B. Vellas
J Prev Alz Dis 2018;5(2):95-97Show summaryHide summary
A.J. Sinclair ; B. Vellas (2018): Diabetes Mellitus and Cognitive Decline – Prevention Should Not Be Delayed!. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2018.9
CTAD Task Force
IDENTIFYING BETTER OUTCOME MEASURES TO IMPROVE TREATMENT OF AGITATION IN DEMENTIA: A REPORT FROM THE EU/US/CTAD TASK FORCE
M. Sano, M. Soto, M. Carrillo, J. Cummings, S. Hendrix, J. Mintzer, A. Porsteinsson, P. Rosenberg, L. Schneider, J. Touchon, P. Aisen, B. Vellas, C. Lyketsos, and the EU/US/CTAD Task Force members
J Prev Alz Dis 2018;5(2):98-102Show summaryHide summary
For the second time in the past 3 years, the EU-US CTAD Task Force addressed challenges related to designing clinical trials for agitation in dementia, which is one of the most disruptive aspects of the condition for both patients and caregivers. Six recommendations emerged from the Task Force meeting: 1 – Operationalizing agitation criteria established by the IPA; 2 – Combining clinician- and caregiver-derived outcomes as primary outcome measures; 3 – Using global ratings to define clinically meaningful effects and power studies; 4 – Improving the accuracy of caregiver reports by better training and education of caregivers; 5 – Employing emerging technologies to collect near real-time behavioral data; and 6 – Utilizing innovative trial designs and increasing the use of biomarkers to maximize the productivity of clinical trials for neuropsychiatric symptoms.
M. Sano ; M. Soto ; M. Carrillo ; J. Cummings ; S. Hendrix ; J. Mintzer ; A. Porsteinsson ; P. Rosenberg ; L. Schneider ; J. Touchon ; P. Aisen ; B. Vellas ; C. Lyketsos ; and the EU/US/CTAD Task Force members (2018): Identifying Better Outcome Measures to Improve Treatment of Agitation in Dementia: 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.2018.15
BIOMARKER AND CLINICAL TRIAL DESIGN SUPPORT FOR DISEASE-MODIFYING THERAPIES: REPORT OF A SURVEY OF THE EU/US: ALZHEIMER’S DISEASE TASK FORCE
J. Cummings, N. Fox, B. Vellas, P. Aisen, G. Shan, for the EU/US Alzheimer’ Disease Task Force
J Prev Alz Dis 2018;5(2):103-109Show summaryHide summary
BACKGROUND: Disease-modifying therapies are urgently needed for the treatment of Alzheimer’s disease (AD). The European Union/United States (EU/US) Task Force represents a broad range of stakeholders including biopharma industry personnel, academicians, and regulatory authorities.
OBJECTIVES: The EU/US Task Force represents a community of knowledgeable individuals who can inform views of evidence supporting disease modification and the development of disease-modifying therapies (DMTs). We queried their attitudes toward clinical trial design and biomarkers in support of DMTs.
DESIGN/SETTING/PARTICIANTS: A survey of members of the EU/US Alzheimer’s Disease Task Force was conducted. Ninety-three members (87%) responded. The details were analyzed to understand what clinical trial design and biomarker data support disease modification.
MEASUREMENTS/RESULTS/CONCLUSIONS: Task Force members favored the parallel group design compared to delayed start or staggered withdrawal clinical trial designs to support disease modification. Amyloid biomarkers were regarded as providing mild support for disease modification while tau biomarkers were regarded as providing moderate support. Combinations of biomarkers, particularly combinations of tau and neurodegeneration, were regarded as providing moderate to marked support for disease modification and combinations of all three classes of biomarkers were regarded by a majority as providing marked support for disease modification. Task Force members considered that evidence derived from clinical trials and biomarkers supports clinical meaningfulness of an intervention, and when combined with a single clinical trial outcome, nearly all regarded the clinical trial design or biomarker evidence as supportive of disease modification. A minority considered biomarker evidence by itself as indicative of disease modification in prevention trials. Levels of evidence (A,B,C) were constructed based on these observations.
CONCLUSION: The survey indicates the view of knowledgeable stakeholders regarding evidence derived from clinical trial design and biomarkers in support of disease modification. Results of this survey can assist in designing clinical trials of DMTs.
J. Cummings ; N. Fox ; B. Vellas ; P. Aisen ; G. Shan ; for the EU/US Alzheimer’ Disease Task Force (2018): Biomarker and Clinical Trial Design Support for Disease-Modifying Therapies: Report of a Survey of the EU/US: Alzheimer’s Disease Task Force. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2018.13
MINIMIZING THE SAMPLE SIZES OF CLINICAL TRIALS ON PRECLINICAL AND EARLY SYMPTOMATIC STAGE OF ALZHEIMER DISEASE
J. Luo, H. Weng, J.C. Morris, C. Xiong
J Prev Alz Dis 2018;5(2):110-119Show summaryHide summary
Background: Clinical trials of investigational drugs for Alzheimer disease (AD) increasingly focus on the prodromal (symptomatic) stage of the illness and now its preclinical (asymptomatic) stage. Sensitive and specific cognitive and functional endpoints are needed to track subtle cognitive and functional changes in the early and preclinical stages to minimize sample sizes in these trials.
Objectives: To identify informative items in a standard clinical assessment protocol and a psychometric battery that are predictive of onset of dementia symptom.
Design: Longitudinal retrospective study.
Setting: Washington University (WU) Knight Alzheimer Disease Research Center (ADRC).
Participants: A total of 735 individuals at least 65 years old and cognitively normal at baseline from a longitudinal clinical cohort at the WU Knight ADRC.
Measurements: The annual clinical assessment included a wide spectrum of functional and cognitive domains; a comprehensive psychometric battery was completed about 2 weeks after the clinical evaluation. Psychometricians are blinded to the results of the clinical evaluation and to the prior performance of the participants on the psychometric tests.
Results: The mean age at baseline of the 735 participants was 74.30 and 62.31% were female. 240 individuals developed prodromal dementia symptoms (consistent with mild cognitive impairment due to AD and with very mild AD dementia) during longitudinal follow-up (mean follow-up=6.79 years). Among a total of 562 items in the clinical and cognitive assessments under analysis, 292 (52%) were identified as informative because their longitudinal changes were predictive of symptomatic onset. When these items were used to form the functional and cognitive composites, the longitudinal rates of changes were free of a learning effect and captured subtle longitudinal progression prior to symptomatic onset. The rates of change were much greater right after the symptomatic onset than those from the functional and cognitive composites formed using non-informative items. Although the sample sizes for prevention trials (prior to symptomatic onset) using the informative items still yield large numbers, the sample sizes for early treatment trial (after symptomatic onset) was much smaller than those derived from all the items or from the non-informative items alone.
Conclusions: The antecedent longitudinal changes in nearly half of the items in a clinical assessment protocol and a comprehensive cognitive battery did not show statistically significant ability to predict the dementia symptom onset, and hence may be non-informative to track the preclinical functional and cognitive progression of AD. The remaining items, on the other hand, captured some of the preclinical changes prior to the symptom onset, but performed much better right after the symptom onset. Currently ongoing prevention trials on preclinical AD of elderly individuals may need to re-assess the sample sizes and statistical power.
J. Luo ; H. Weng ; J.C. Morris ; C. Xiong (2018): Minimizing the Sample Sizes of Clinical Trials on Preclinical and Early Symptomatic Stage of Alzheimer Disease. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2018.16
A LITERATURE REVIEW OF METHODOLOGIES USED IN RANDOMIZED CLINICAL TRIALS OF AGITATION IN ALZHEIMER’S DISEASE
S. Dubé, J.T. Megerian, R. Malamut
J Prev Alz Dis 2018;5(2):120-133Show summaryHide summary
Agitation is a common and burdensome symptom associated with Alzheimer’s disease (AD). This is a narrative literature review of the designs and methods used in randomized clinical trials of agitation in patients with AD; sources range from published, to completed but not published, to ongoing studies in the past 10 years. Selection for review included blinded, randomized trials conducted to assess the effect of a pharmacological intervention for which agitation in patients with AD was among the prespecified end points. Key criteria for exclusion included open-label studies, trials of dementia not specific to AD, or mixed populations of AD and unspecified dementia. A search of PubMed and clinicaltrials.gov databases identified 36 trials for which agitation was among the prespecified end points: 18 were published trials and 18 were completed but not published or ongoing. There was significant heterogeneity among AD studies in terms of diagnostic criteria, assessment of severity of disease and agitation, sample size and powering assumptions, treatment duration, patient age and cognitive status, and outcomes measurements. Few studies used a mitigation strategy for placebo response. Accumulating evidence suggests that it is important to consider the following in trial design: thresholds for baseline severity of agitation and AD; use of prespecified accepted criteria to define agitation; and use of standardized, validated tools to measure treatment effects during a trial. Adoption of these design strategies might help improve signal detection and bring us closer to identifying the most appropriate, effective, and safe treatments for agitation in patients with AD.
S. Dubé ; J.T. Megerian ; R. Malamut (2018): A Literature Review of Methodologies Used in Randomized Clinical Trials of Agitation in Alzheimer’s Disease. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2018.17
THE INTEGRATED ALZHEIMER’S DISEASE RATING SCALE (IADRS) FINDINGS FROM THE EXPEDITION3 TRIAL
A.M. Wessels, S.W. Andersen, S.A. Dowsett, E.R. Siemers
J Prev Alz Dis 2018;5(2):134-136Show summaryHide summary
The Integrated Alzheimer’s Disease (AD) Rating Scale (iADRS) is a composite tool that combines scores from the AD Assessment Scale-Cognitive subscale (ADAS-Cog) and the AD Cooperative Study - instrumental Activities of Daily Living (ADCS-iADL). It demonstrates acceptable psychometric properties, and is effective in capturing both disease progression and separation of placebo and active drug effect. We assessed the performance of iADRS in the solanezumab EXPEDITION3 study, an 80-week, placebo-controlled study of individuals with mild AD dementia. A statistically significant difference between placebo and active drug was observed for iADRS score change from baseline at Week 28 (p=0.028) through Week 80 (p=0.015). Across the Phase 3 solanezumab trials, iADRS was the only tool that consistently differentiated between solanezumab and placebo groups. These findings suggest that the iADRS is a useful integrated measurement tool for treatment trials of individuals with mild AD dementia.
A.M. Wessels ; S.W. Andersen ; S.A. Dowsett ; E.R. Siemers (2018): The Integrated Alzheimer’s Disease Rating Scale (iADRS) Findings from the EXPEDITION3 Trial. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2018.10
ADHERENCE TO THE MEDITERRANEAN DIET IS NOT RELATED TO BETA-AMYLOID DEPOSITION: DATA FROM THE WOMEN’S HEALTHY AGEING PROJECT
E. Hill, C. Szoeke, L. Dennerstein, S. Campbell, P. Clifton
J Prev Alz Dis 2018;5(2):137-141Show summaryHide summary
Background: Research has indicated the neuroprotective potential of the Mediterranean diet. Adherence to the Mediterranean diet has shown preventative potential for Alzheimer’s disease incidence and prevalence, yet few studies have investigated the impact of Mediterranean diet adherence on the hallmark protein; beta-amyloid.
Objectives: To investigate the association between Mediterranean diet adherence and beta-amyloid deposition in a cohort of healthy older Australian women.
Design: This study was a cross-sectional investigation of participants from the longitudinal, epidemiologically sourced Women’s Healthy Ageing Project which is a follow-up of the Melbourne Women’s Midlife Health Project.
Setting: Assessments were conducted at the Centre for Medical Research, Royal Melbourne Hospital in Melbourne, Australia. F-18 Florbetaben positron emission tomography scanning was conducted at the Austin Centre for PET in Victoria, Australia.
Participants: One hundred and eleven Women’s Healthy Ageing Project participants were included in the study.
Measurements: Mediterranean diet adherence scores for all participants were calculated from the administration of a validated food frequency questionnaire constructed by the Cancer Council of Victoria. Beta-amyloid deposition was measured using positron emission tomography standardised uptake value ratios.
Results: Gamma regression analysis displayed no association between Mediterranean diet adherence and beta-amyloid deposition. This result was consistent across APOE-ε4 +/- cohorts and with the inclusion of covariates such as age, education, body mass index and cognition.
Conclusions: This study found no association between adherence to the Mediterranean diet and beta-amyloid deposition in a cohort of healthy Australian women.
E. Hill ; C. Szoeke ; L. Dennerstein ; S. Campbell ; P. Clifton (2018): Adherence to the Mediterranean Diet Is not Related to Beta-Amyloid Deposition: Data from the Women’s Healthy Ageing Project. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2018.12
STRONG RELATIONSHIP BETWEEN MALNUTRITION AND COGNITIVE FRAILTY IN THE SINGAPORE LONGITUDINAL AGEING STUDIES (SLAS-1 AND SLAS-2)
L. Chye, K. Wei, M.S.Z. Nyunt, Q. Gao, S.L. Wee, T.P. Ng
J Prev Alz Dis 2018;5(2):142-148Show summaryHide summary
Background: Physical frailty is well known to be strongly associated with malnutrition, but the combined impact of physical frailty and cognitive impairment among non-demented older persons (cognitive frailty) on malnutrition prevalence is not well documented.
Design: Cross-sectional cohort study.
Setting and Participants: Community-dwelling older Singaporeans aged ≥55y (n=5414) without dementia in the Singapore Longitudinal Ageing Study (SLAS-1 and SLAS-2).
Measurements: The Mini Nutritional Assessment – short form (MNA-SF) and Nutrition Screening Initiative (NSI) Determine Checklist were used to determine their nutritional status. Participants were categorized as cognitive normal (CN) or cognitive impaired (CI) by Mini Mental State Examination (MMSE<=23), as pre-frail (PF) (score=1-2) or frail (F) (score=3-5) using Fried’s criteria, and as cognitive pre-frail (PF+CI) or cognitive frail (F+CI).
Results: The prevalence of cognitive frailty was 1.6%, and cognitive pre-frailty was 5.5% (total, 7.1%). The prevalence of MNA malnutrition was 2.4%, and NSI high nutritional risk was 6.3%. The prevalence of MNA malnutrition was lowest among Robust-CN and highest among Frail-CI (0.5% in Robust-CN, 0.6% in Robust-CI, 2.8% in Pre-frail-CN, 7.3% in Pre-frail-CI, 15.4% in Frail-CN, and 23.1% in Frail-CI). Similarly, the prevalence of NSI high nutritional risk was lowest in Robust-CN (3.7%) and highest in Frail-CI (13.6%). Adjusted for sociodemographic and health status, pre-frailty/frailty-CI versus Robust-CN was associated with the highest odds ratio of association with MNA malnutrition (OR=8.16, p<0.001), although not the highest with NSI high nutritional risk (OR=1.48, p=0.017).
Conclusions: An extraordinary high prevalence of malnutrition was observed among older adults with cognitive frailty who should be specially targeted for active intervention.
L. Chye ; K. Wei ; M.S.Z. Nyunt ; Q. Gao ; S.L. Wee ; T.P. Ng (2017): Strong Relationship between Malnutrition and Cognitive Frailty in the Singapore Longitudinal Ageing Studies (SLAS-1 and SLAS-2). The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2017.46
DEVELOPMENT OF AZELIRAGON, AN ORAL SMALL MOLECULE ANTAGONIST OF THE RECEPTOR FOR ADVANCED GLYCATION ENDPRODUCTS, FOR THE POTENTIAL SLOWING OF LOSS OF COGNITION IN MILD ALZHEIMER’S DISEASE
A.H. Burstein, M. Sabbagh, R. Andrews, C. Valcarce, I. Dunn, L. Altstiel
J Prev Alz Dis 2018;5(2):149-154Show summaryHide summary
Increasing evidence supports the role of the Receptor for Advanced Glycation Endproducts (RAGE) in the pathology of Alzheimer’s disease. Azeliragon (TTP488) is an orally bioavailable small molecule inhibitor of RAGE in Phase 3 development as a potential treatment to slow disease progression in patients mild AD. Preclinical studies in animal models of AD (tgAPPSwedish/London) have shown azeliragon to decrease Aβ plaque deposition; reduce total Aβ brain concentration while increasing plasma Aβ levels; decreases sAPPβ while increasing sAPPα; reduce levels of inflammatory cytokines; and slow cognitive decline and improve cerebral blood flow. In the Phase 2b study, 18-months treatment in patients with mild-to-moderate AD indicated a baseline to endpoint change in ADAS-cog of 3.1 points in favor of drug. A greater magnitude of effect was evident in the sub-group of patients with mild AD (MMSE 21-26) with a baseline to endpoint change of 4 points on the ADAS-cog in favor of azeliragon and a 1 point change in CDR-sb in favor of drug. Azeliragon 5 mg/day delayed time to cognitive deterioration (7-point change in ADAS-cog from baseline, logrank p=0.0149). Based on promising results from the Phase 2b study, a Phase 3 registration program (STEADFAST) is being conducted under a Special Protocol Assessment from FDA. The ongoing Phase 3 program, if successful may demonstrate azeliragon can slow cognitive decline in mild AD patients.
A.H. Burstein ; M. Sabbagh ; R. Andrews ; C. Valcarce ; I. Dunn ; L. Altstiel (2018): Development of Azeliragon, an Oral Small Molecule Antagonist of the Receptor for Advanced Glycation Endproducts, for the Potential Slowing of Loss of Cognition in Mild Alzheimer’s Disease. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2018.18
Letter to the Editor
NANOROBOTS THE FUTURE OF NEUROLOGY: A PERSPECTIVE ON ALZHEIMER’S DISEASE
C. Hooper, S. Layé
J Prev Alz Dis 2018;5(2):155-156Show summaryHide summary
C. Hooper ; S. Layé ; (2018): Nanorobots the Future of Neurology: A Perspective on Alzheimer’s Disease. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2018.6