01/2015 journal articles
ESTABLISHING COMPOSITE COGNITIVE ENDPOINTS FOR USE IN PRECLINICAL ALZHEIMER’S DISEASE TRIALS
J.B. Langbaum, S. Hendrix, N. Ayutyanont, D. A. Bennett, R.C. Shah, L.L. Barnes, F. Lopera, E.M. Reiman, P.N. Tariot
J Prev Alz Dis 2015;2(1):2-3Show summaryHide summary
J.B. Langbaum, ; S. Hendrix, ; N. Ayutyanont, ; D. A. Bennett, ; R.C. Shah, ; L.L. Barnes, ; F. Lopera, ; E.M. Reiman, ; P.N. Tariot (2015): ESTABLISHING COMPOSITE COGNITIVE ENDPOINTS FOR USE IN PRECLINICAL ALZHEIMER’S DISEASE TRIALS. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2015.46
INVESTIGATING FUNCTIONAL IMPAIRMENT IN PRECLINICAL ALZHEIMER’S DISEASE
J Prev Alz Dis 2015;2(1):4-6Show summaryHide summary
D. Marson (2015): INVESTIGATING FUNCTIONAL IMPAIRMENT IN PRECLINICAL ALZHEIMER’S DISEASE. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2015.44
THINKING ABOUT COGNITIVE FRAILTY
J Prev Alz Dis 2015;2(1):7-10Show summaryHide summary
L.J. Fitten (2015): THINKING ABOUT COGNITIVE FRAILTY. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2015.45
BASELINE SUBJECTIVE MEMORY COMPLAINTS ASSOCIATE WITH INCREASED RISK OF INCIDENT DEMENTIA: THE PREADVISE TRIAL
E.L. Abner, R.J. Kryscio, A.M. Caban-Holt, F.A. Schmitt
J Prev Alz Dis 2015;2(1):11-16Show summaryHide summary
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.
E.L. Abner ; R.J. Kryscio ; A.M. Caban-Holt ; F.A. Schmitt (2015): Baseline Subjective Memory Complaints Associate with Increased Risk of Incident Dementia: The PREADVISE Trial. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2015.37
MEMORY BROUGHT TO MIND. FIVE-YEAR FOLLOW-UP OF CASE FINDING AND INTERVENTION OF DEMENTIA IN A SWEDISH PRIMARY HEALTH CARE DISTRICT
S. Josefsson, M. Kjellmark, P. Adenmark, E. Karlsson, R. Åstrand, E. Trell
J Prev Alz Dis 2015;2(1):17-23Show summaryHide summary
BACKGROUND: In an urban/rural primary health care (PHC) district a five-year integrated project of early detection and management of cognitive disorders was made in collaboration between home care (HC) and family practice services using a single-item case-finding and intervention approach.
OBJECTIVES: To assess feasibility, outcome and morbidity over a 5-year period.
DESIGN, SETTING AND PARTICIPANT: In autumn 2008, the question “Have you experienced memory difficulties or been told of them by family members?” was mailed to all eligible persons > 75 years of age (n=367) in the urban/rural Vålberg HC and PHC district (population = 5073). 320 (= 87%; 184 no and 136 yes) responded and 117 yes-responders came for further examination. In the follow-up, all diagnoses up till November 2013 were collected and compared anonymously in both yes and no answerers.
RESULTS: 114 completed examination. 29 showed low risk of cognitive impairment, 39 moderate and 46 high. Definitive diagnosis was obtained in 34 of the latter: 10 cognitive impairment, 16 Alzheimer’s disease, 5 non-specific, 2 vascular and 1 alcoholic dementia. During follow-up no further dementia diagnoses occurred in the low, two in the moderate, and none in the high-risk group, versus 12 in the no responders. Age and mortality were significantly higher in the high-risk group. Co-morbidity was very frequent but did not differ between the groups.
CONCLUSIONS: Population response and compliance were excellent; the single-item direct question approach gave workable results with in particular high negative predictive power persisting over the five-year follow-up period, and can be applied in early case-finding, prevention and intervention of cognitive impairment in an integrated local HC, PHC and Hospital setting.
S. Josefsson ; M. Kjellmark ; P. Adenmark ; E. Karlsson ; R. Åstrand ; E. Trell (2015): MEMORY BROUGHT TO MIND. FIVE-YEAR FOLLOW-UP OF CASE FINDING AND INTERVENTION OF DEMENTIA IN A SWEDISH PRIMARY HEALTH CARE DISTRICT. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2015.43
HIGHER COGNITIVE PERFORMANCE IS PROSPECTIVELY ASSOCIATED WITH HEALTHY DIETARY CHOICES: THE MAINE SYRACUSE LONGITUDINAL STUDY
G.E. Crichton, M.F. Elias , A. Davey , A. Alkerwi , G.A. Dore
J Prev Alz Dis 2015;2(1):24-32Show summaryHide summary
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.
G.E. Crichton ; M.F. Elias ; A. Davey ; A. Alkerwi ; G.A. Dore (2015): Higher cognitive performance is prospectively associated with healthy dietary choices: The Maine Syracuse Longitudinal Study. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2015.39
EFFECT OF PUNICALAGIN AND RESVERATROL ON METHIONINE SULFOXIDE REDUCTASE: A POSSIBLE PROTECTIVE CONTRIBUTION AGAINST ALZHEIMER DISEASE
M.E. Clementi, B. Sampaolese, G. Lazzarino, B. Giardina
J Prev Alz Dis 2015;2(1):33-37Show summaryHide summary
Methionine sulfoxide reductase A (MsrA) has been postulated to act as a catalytic antioxidant system involved in the protection of oxidative stress-induced cell injury. MsrA has recently turned attention in coupling with the neurodegenerative disorders and in particular with Alzheimer disease. In fact this neurodegenerative disorder depends to a deposit of beta amyloid a peptide with an oxidizable methionine in position 35 which is proved able to modulate the expression to MsrA in neuronal cells. Here, we firstly provided evidence that pretreatment with Resveratrol and Punicalagin (a potent antioxidant extracted from pomegranate), up-regulate the expression and enzymatic activity of MsrA in human neuroblastoma IMR-32 cells with beta amyloid peptides. This effect determines a lowering of oxidative potential of the cells as demonstrated by the ROS measurement and a protective effect on cellular availability. Therefore we hypothesize a possible prevent role for these molecules in Alzheimer and in other neurodegenerative diseases.
M.E. Clementi ; B. Sampaolese ; G. Lazzarino ; B. Giardina (2015): Effect of Punicalagin and Resveratrol on Methionine Sulfoxide Reductase: a possible protective contribution against Alzheimer Disease. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2015.40
INTERVENTIONS TO PREVENT COGNITIVE DECLINE AND DEMENTIA IN ADULTS WITHOUT COGNITIVE IMPAIRMENT: A SYSTEMATIC REVIEW
J.C. Barnett, A. Bahar-Fuchs, N. Cherbuin, P. Herath, K.J. Anstey
J Prev Alz Dis 2015;2(1):38-45Show summaryHide summary
Without preventative strategies, the burden of dementia is likely to increase rapidly worldwide. Primary prevention approaches involve modifying risk factors before symptoms of cognitive impairment develop. This review systematically assesses Randomised Controlled Trials (RCTs) and reviews of RCTs for their effectiveness in primary prevention. We searched Medline, the Cochrane Library, Web of Science and Psych-Info for relevant studies using pre-determined keywords. Both non-pharmacological and pharmacological interventions were considered. Inclusion criteria were sample size greater or equal to 50, at least 6 months of follow-up, and participants with no cognitive impairment at baseline. Outcomes included
dementia incidence, cognitive decline and cognitive function. Study quality was rated using the Jadad criteria. Thirty-nine studies, 17 non-pharmacological and 22 pharmacological, were included. Results were heterogeneous across interventions and studies, with few significant effects. Studies investigating physical activity and calcium channel blocker treatment demonstrated significant effects in preventing cognitive decline. There were no conclusive results demonstrating overall capacity of assessed interventions to reduce risk of dementia. The review provides an overview of the current literature, and identifies areas in need of further research.
J.C. Barnett ; A. Bahar-Fuchs ; N. Cherbuin ; P. Herath ; K.J. Anstey ; (2015): Interventions to prevent cognitive decline and dementia in adults without cognitive impairment: A systematic review. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2015.36
AMYLOID AND TAU BIOMARKERS IN CSF
K. Blennow, H. Zetterberg
J Prev Alz Dis 2015;2(1):46-50Show summaryHide summary
The number of failed Alzheimer’s disease (AD) clinical trials on Aβ-targeting drugs is increasing. The explanation for this is most likely multi-factorial. An optimistic standpoint is that trials have to be on patients in an earlier stage of the disease, before neurodegeneration is too severe, to show efficacy, and probably also of longer duration. Further, there is a general agreement that enrolled patients have to be diagnosed based on combined clinical and biomarker criteria, to avoid noise from the large proportion (20%) of cases that are misdiagnosed if only clinical criteria are used. Last, the poor predictive power of translating an “anti-Aβ” or “anti-plaque” effect from AD transgenic animal models to AD patients also calls for biomarkers to verify target engagement in man, and to show downstream effects of Aβ-targeting drug candidates in AD patients. The focus of this review is on the possible role of cerebrospinal fluid (CSF) biomarkers in AD clinical trials for diagnostics, and thus patient enrichment, and for theragnostics, to provide evidence of target engagement of the drug on Aβ metabolism or aggregation, and of effects on the molecular pathology of the disease.
K. Blennow ; H. Zetterberg (2015): Amyloid and Tau Biomarkers in CSF. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2015.41
BEYOND THE CONTROVERSY ON Aß BLOOD-BASED BIOMARKERS
P. Pesini, M. Sarasa
J Prev Alz Dis 2015;2(1):51-55Show summaryHide summary
Central biomarkers of Alzheimer’s disease (AD) have been proven to have diagnostic and prognostic capacity. However, both amyloid positron emission tomography and cerebrospinal fluid collection studies present problems that limit their widespread acceptability in global clinical trials. Thus, development of other measures as potential surrogates of amyloid positivity should be pursued. Results from numerous experimental studies strongly suggest that the association between Aβ plasma levels, particularly the Aβ42/Aβ40 ratio, and AD diagnosis goes beyond what could be attributable to pure chance, although this association is still controversial. The aim of this review is to consider selected works that may help to improve the design of blood based biomarkers studies by controlling a number of confounding sources related to the clinical gold standard, the time-course of central and peripheral biomarkers, and the metabolism of Aβ in blood that may be blurring the presumptive association between Aβ blood levels and AD. Based on these data and to get pass the controversy, we tentatively postulate that at early stages of preclinical AD, blood Aβ levels and central Aβ biomarkers would follow parallel but temporally displaced trajectories. This association would become eventually lost as the disease progresses and the clearance mechanisms in the blood brain barrier are increasingly impaired.
P. Pesini ; M. Sarasa ; (2015): BEYOND THE CONTROVERSY ON AΒ BLOOD-BASED BIOMARKERS. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2015.35
PHYSICAL ACTIVITY AND ß-AMYLOID BRAIN LEVELS IN HUMANS: A SYSTEMATIC REVIEW
P. de Souto Barreto, B. Vellas, S. Andrieu, Y. Rolland
J Prev Alz Dis 2015;2(1):56-63Show summaryHide summary
Physical activity (PA) contributes to brain health and plasticity, which suggests that PA would protect against the development of Alzheimer’s disease (AD). However, research on PA and AD biomarkers is very scarce. The objective of the present study was to perform a systematic review of studies that investigated the associations between PA and β-amyloid brain deposition in humans. Electronic searches were performed in PubMed, Cochrane Library, SportDiscus, PEDro, and PsychInfo databases. Articles were eligible if they have assessed both PA and β-amyloid brain deposition in humans. Five articles, published between 2010 and 2013, met eligibility criteria (study population varied across studies from 54 to 515, according with the β-amyloid measure. All five studies assessed both PA and PET-amyloid; among them, two studies also assessed CSF Aβ42 levels). All studies were based on cross-sectional data, from non-demented populations. Among the five included studies, three found significant associations between PA and β-amyloid brain deposition, and the other two did not find any significant association; limited evidence suggests that PA-amyloid plaques associations would be APOE ε4 allele-specific. In sum, no solid conclusions can be drawn on the associations between PA and human β-amyloid brain deposition currently. Future research on this topic should particularly pay attention to the operationalisation of clinically relevant and valid PA variables and should include important confounders in multivariate analysis. More information is needed on the potential interactions between PA and other AD risk factors (e.g., cognitive activities, APOE ε4 status, nutrition, smoking) and their combined effects on AD biomarkers.
P. de Souto Barreto ; B. Vellas ; S. Andrieu ; Y. Rolland ; (2015): PHYSICAL ACTIVITY AND B-AMYLOID BRAIN LEVELS IN HUMANS: A SYSTEMATIC REVIEW. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2015.34
IMAGING VASCULAR DISEASE AND AMYLOID IN THE AGING BRAIN: IMPLICATIONS FOR TREATMENT
S. Villeneuve, W.J. Jagust
J Prev Alz Dis 2015;2(1):64-70Show summaryHide summary
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.
S. Villeneuve ; W.J. Jagust (2015): IMAGING VASCULAR DISEASE AND AMYLOID IN THE AGING BRAIN: IMPLICATIONS FOR TREATMENT. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2015.47
COMMUNITY-BASED INTERVENTION FOR PREVENTION OF DEMENTIA IN JAPAN
T. Suzuki, H. Makizako, T. Doi, H. Park, S. Lee, K. Tsutsumimoto, K. Umemura, Y. Maki, H. Shimada
J Prev Alz Dis 2015;2(1):71-76Show summaryHide summary
Population aging is accelerating, with prolonged life expectancy and a decrease in birth rate. As age is a significant risk factor for dementia, we are confronted with an ever-increasing prevalence of mild cognitive impairment (MCI)/dementia. Thus, the Japanese National Center for Geriatrics and Gerontology launched a project to promote community-based research, including the development of an effective screening system for high-risk groups and intervention for dementia prevention. This review introduces the project, the Obu Study of Health Promotion for the Elderly, with the following strategic triad: 1) Identification of the target population by population screening; we regarded patients with MCI as the target population, and developed a screening test battery to identify MCI in a population screening setting. 2) Scientific evaluation of community-based intervention; we developed an interventional method combining exercise and cognitive training (“cognicise”). In practical settings, “cognicise” is programmed into multicomponent exercise intervention, which was reported to have benefits of cognitive improvement and reduction of brain atrophy based on randomized controlled trials. 3) Standardization of the methods of population screening and community-based intervention for evidence-based policy making and widespread implementation. Dementia prevention, or at least delaying the onset of dementia and/or stopping/slowing the progression of dementia, should benefit the whole society as well as individuals. It is our continuing challenge to improve the screening system and community-based intervention for dementia prevention through accumulation of evidence .
T. Suzuki ; H. Makizako ; T. Doi ; H. Park ; S. Lee ; K. Tsutsumimoto ; K. Umemura ; Y. Maki ; H. Shimada (2015): Community-Based Intervention for Prevention of Dementia in Japan. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2015.42