scholarly journals Disease Modelling of Cognitive Outcomes and Biomarkers in the European Prevention of Alzheimer’s Dementia Longitudinal Cohort

2021 ◽  
Vol 4 ◽  
Author(s):  
James Howlett ◽  
Steven M. Hill ◽  
Craig W. Ritchie ◽  
Brian D. M. Tom
Keyword(s):  
Disease Process ◽  
Alzheimer’S Dementia ◽  
Rate Of Change ◽  
Cognitive Outcomes ◽  
Disease Modelling ◽  
Data Set ◽  
Alzheimer's Dementia ◽  
Longitudinal Cohort ◽  
Wide Range

A key challenge for the secondary prevention of Alzheimer’s dementia is the need to identify individuals early on in the disease process through sensitive cognitive tests and biomarkers. The European Prevention of Alzheimer’s Dementia (EPAD) consortium recruited participants into a longitudinal cohort study with the aim of building a readiness cohort for a proof-of-concept clinical trial and also to generate a rich longitudinal data-set for disease modelling. Data have been collected on a wide range of measurements including cognitive outcomes, neuroimaging, cerebrospinal fluid biomarkers, genetics and other clinical and environmental risk factors, and are available for 1,828 eligible participants at baseline, 1,567 at 6 months, 1,188 at one-year follow-up, 383 at 2 years, and 89 participants at three-year follow-up visit. We novelly apply state-of-the-art longitudinal modelling and risk stratification approaches to these data in order to characterise disease progression and biological heterogeneity within the cohort. Specifically, we use longitudinal class-specific mixed effects models to characterise the different clinical disease trajectories and a semi-supervised Bayesian clustering approach to explore whether participants can be stratified into homogeneous subgroups that have different patterns of cognitive functioning evolution, while also having subgroup-specific profiles in terms of baseline biomarkers and longitudinal rate of change in biomarkers.

scholarly journals European Prevention of Alzheimer’s Dementia Longitudinal Cohort Study (EPAD LCS): study protocol

BMJ Open ◽  
2018 ◽  
Vol 8 (12) ◽  
pp. e021017 ◽  
Author(s):  
Alina Solomon ◽  
Miia Kivipelto ◽  
José Luis Molinuevo ◽  
Brian Tom ◽  
Craig W Ritchie
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cohort Study ◽  
Alzheimer’S Dementia ◽  
Longitudinal Cohort Study ◽  
Community Research ◽  
Data Set ◽  
Alzheimer's Dementia ◽  
Longitudinal Cohort ◽  
Research Participants

IntroductionThe European Prevention of Alzheimer’s Dementia (EPAD) project is funded initially by the Innovative Medicines Initiative and has been established to overcome the major hurdles hampering drug development for secondary prevention of Alzheimer’s dementia, by conducting the EPAD Longitudinal Cohort Study (LCS) in alignment with the Bayesian adaptive designed EPAD Proof-of-Concept (PoC) trial.Methods and analysisEPAD LCS is an ongoing prospective, multicentre, pan-European longitudinal cohort study. Participants are recruited mainly from existing parent cohorts across Europe to form a ‘probability-spectrum’ population covering the entire continuum of anticipated probability for Alzheimer’s dementia development. The primary objective of the EPAD LCS is to be a readiness cohort for the EPAD PoC trial though a second major objective is to generate a comprehensive and large data set for disease modelling of preclinical and prodromal Alzheimer’s disease. This characterisation of cognitive, biomarker and risk factor (genetic and environmental) status of research participants over time will provide the necessary well-phenotyped population for developing accurate longitudinal models for Alzheimer’s disease covering the entire disease course and concurrently create a pool of highly characterised individuals for the EPAD PoC trial.Ethics and disseminationThe study has received the relevant approvals from numerous Institutional Review Boards across Europe. Findings will be disseminated to several target audiences, including the scientific community, research participants, patient community, general public, industry, regulatory authorities and policy-makers. Regular and coordinated releases of EPAD LCS data will be made available for analysis to help researchers improve their understanding of early Alzheimer’s disease stages and facilitate collaborations.Trial registration numberNCT02804789.

scholarly journals THE EUROPEAN PREVENTION OF ALZHEIMER’S DEMENTIA (EPAD) LONGITUDINAL COHORT STUDY: BASELINE DATA RELEASE V500.0

2019 ◽  
pp. 1-7 ◽  
Author(s):  
C.W. Ritchie ◽  
G. Muniz-Terrera ◽  
M. Kivipelto ◽  
A. Solomon ◽  
B. Tom ◽  
...  
Keyword(s):  
Cohort Study ◽  
Primary Objective ◽  
Alzheimer’S Dementia ◽  
Longitudinal Cohort Study ◽  
Alzheimer's Dementia ◽  
Longitudinal Cohort ◽  
Research Participants ◽  
Future Design ◽  
Preclinical Ad ◽  
Data Release

Background: The European Prevention of Alzheimer’s Dementia (EPAD) Programme is a pan-European project whose objective is to deliver a platform, adaptive, Phase 2 proof of concept (PoC) trial for the secondary prevention of Alzheimer’s dementia. A component of this platform is the Longitudinal Cohort Study (LCS) which acts as a readiness cohort for the PoC Trial as well as generating data for disease modelling work in the preclinical and prodromal phases of Alzheimer’s dementia. Objectives: The first data wave has been collected, quality checked, released and now available for analysis to answer numerous research questions. Here we describe the results from key variables in the EPAD LCS with the objective of using these results to compliment analyses of these data in the future. Design: EPAD LCS is a cohort study whose primary objective is as a readiness cohort for the EPAD PoC Trial. As such recruitment is not capped at any particular number but will continue to facilitate delivery of the EPAD PoC Trial. Research Participants are seen annually (with an additional 6 month visit in the first year). Setting: The EPAD Trial Delivery Network comprises currently 21 centres across Europe. Participants: Research participants are included if they are over 50 years old and do not have a diagnosis of dementia. Measurements: All research participants undergo multiple assessments to fully characterise the biology of Alzheimer’s disease and relate this to risk factors (both fixed and modifiable) and biomarker expression of disease through brain imaging, fluid samples (CSF, blood, urine and saliva), cognitive performance, functional abilities and neuropsychiatric symptomatology. Results: V500.0 represents the first 500 research participants baselined into EPAD LCS. The mean age was 66.4 (SD=6.7) and 47.8% were male. The data was split for presentation into 4 groups: [1] CDR=0 and Amyloid + (preclinical AD), [2] CDR=0 and Amyloid –, [3] CDR=0.5 and Amyloid + (prodromal AD) and [4] CDR=0.5 and Amyloid -. Conclusions: The EPAD LCS is achieving its primary objective of trial readiness and the structured approach to data release as manifest by this first data release of V500.0 will assist researchers to describe and compare their findings as well as in systematic reviews and meta-analyses. It is anticipated given current recruitment rates that V1500.0 data release will take place in Autumn 2019. V500.1 (when the 1 year follow up is completed on the V500.0 (sub)cohort will be in Autumn 2019 also.

scholarly journals Late Onset Alzheimer Dementia in Patient with Genotype E3/E4: A Case Report

2021 ◽  
Vol 8 (11) ◽  
pp. 282-285
Author(s):  
Irfan Kurnia Kaban ◽  
Yudha Haryono
Keyword(s):  
Apolipoprotein E ◽  
Neurodegenerative Disorder ◽  
Late Onset ◽  
Neurofibrillary Tangle ◽  
Apoe Genotype ◽  
Disease Process ◽  
Alzheimer’S Dementia ◽  
Magnetic Resonance Imaging Examination ◽  
Alzheimer's Dementia ◽  
Alzheimer Dementia

ackground: Alzheimer's dementia (AD) is a neurodegenerative disorder and there is progressive cognitive impairment, functional deficits and behavioral changes. This neurodegenerative disease process is classically characterized by two pathological features: amyloid- β plaque deposition and neurofibrillary tangle of tau hyperphosphorylation. The most established genetic risk factor for late-onset Alzheimer Disease is the APOE gene allele 4. We will report a case of late-onset Alzheimer's Dementia with genotype E3/E4. Case: A 70-years-old woman patient, complained by her family that she often forgets. The Mini Mental State Examination showed disturbances in orientation, attention, calculation and recall. Non-contrast Brain Magnetic resonance imaging examination revealed decrease in hippocampal volume. Patient also performed a molecular examination of the Apolipoprotein E (APOE) genotype and the genotype E3/E4 was detected Conclusion: The APOE E4 gene has a major role in the occurrence of Late-Onset Alzheimer's Dementia. Keywords: Alzheimer Dementia, Apolipoprotein E.

scholarly journals Ocular Exploration in the Diagnosis and Follow-Up of the Alzheimer’s Dementia

2019 ◽  
pp. 159-177 ◽  
Author(s):  
Elena Salobrar-Garcia ◽  
◽  
Rosa de Hoz ◽  
Ana I. Ramírez ◽  
Juan J. Salazar ◽  
...  
Keyword(s):  
Alzheimer’S Dementia ◽  
Alzheimer's Dementia

scholarly journals Mortality rates are higher in lewy body and parkinson's disease dementia compared to Alzheimer's dementia in patients referred into a secondary care mental health service. Why?

BJPsych Open ◽  
2021 ◽  
Vol 7 (S1) ◽  
pp. S262-S262
Author(s):  
Anne K ◽  
John O'Brien ◽  
Annabel Price ◽  
Rudolph Cardinal ◽  
Sinead Moylett
Keyword(s):  
Mental Health ◽  
Mental Health Services ◽  
Health Services ◽  
Lewy Body ◽  
Alzheimer’S Dementia ◽  
Alzheimer's Dementia ◽  
Risk Of Death ◽  
Recurrent Falls ◽  
Males And Females

AimsWe compared survival in four cohorts of dementia patients– Lewy body (LBD), Parkinson's (PDD), Vascular (VD) and Alzheimer's dementia (AD) - in patients referred into Cambridge and Peterborough NHS Foundation Trust (CPFT) mental health services.Additionally, we investigated reasons for variation in survival in the four cohorts.MethodUsing electronic records we identified retrospective cohorts of patients referred into services from 2013 onwards. Cases of LBD and PDD were identified using text searches, and comparison cohorts with AD or VD identified using ICD10 diagnosis codes ((F00.*) or (F01.*) respectively).We collected referral (date of referral and service referred into), demographic (date of birth and gender) and diagnosis data on the patients in the four cohorts. Dates of death were available, through central NHS reporting to Trusts.We used date of first referral as start of the follow-up and end of follow-up, death or 31/12/19. We used Kaplan-Meier and Cox survival analysis to compare survival in the four cohorts.The cohorts were crossed with Hospital Episode Statistics (HES) data to extract hospital admission diagnoses. We extracted diagnoses of pneumonia due to aspiration and recurrent falls from hospital admissions data using ICD codes (J69.0 and R29.6 respectively). We calculated prevalence of these diagnoses in the dementia groups, in males and females separately.ResultIn Cox analysis (controlling for age at referral, gender and service referred into), the hazard ratio (HR) for death was highest for the PDD group (HR 2.0 (95% CI 1.7–2.4)), followed by LBD (HR 1.4 (95% CI 1.3–1.6)), then VD (HR 1.2 (95% CI 1.0–1.3)), with the AD group as reference. In the same analysis repeated separately for males and females, the highest HR was found in males with PDD (HR 2.3 (95% CI 1.8–2.8)).Referrals to liaison psychiatry were associated with reduced survival compared to other mental health services (HR 1.7 (95% CI 1.5–2.0)).The AD cohort showed the lowest rates of pneumonia due to aspiration and recurrent falls in males and in females. The highest rate of pneumonia due to aspiration was found in the male PDD group (27%).ConclusionIn patients with dementia referred into mental health services, those with AD survive longer compared to other dementia groups, with PDD patients at highest risk of death. Physical frailty including risk of aspiration, is likely to account for some of this difference in survival.

Presenile primary cognitive decline or Alzheimer's dementia: 7-year clinical and neuropsychological follow-up

1999 ◽  
Vol 20 (2) ◽  
pp. 109-117 ◽  
Author(s):  
R. Zappoli ◽  
M. Paganini ◽  
G. Arnetoli ◽  
L. Bracco ◽  
A. Battaglia ◽  
...  
Keyword(s):  
Cognitive Decline ◽  
Alzheimer’S Dementia ◽  
Alzheimer's Dementia

scholarly journals https://link.springer.com/article/10.14283/jfa.2020.9

2020 ◽  
pp. 1-2
Author(s):  
E.A. Meyers ◽  
M.C. Carrillo
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Disease Process ◽  
Neuronal Loss ◽  
Alzheimer’S Dementia ◽  
Alzheimer's Dementia ◽  
Minimal Impact ◽  
Research Framework ◽  
Clinical Consequences

Early detection is critical in our fight to stop or slow Alzheimer’s dementia, and even more so to prevent Alzheimer’s disease (AD). Current diagnosis of Alzheimer’s dementia relies largely on documenting mental decline, at which point, severe cognitive and functional damage has occurred. According to the National Institute on Aging and Alzheimer’s Association Research Framework, Alzheimer’s disease is defined by its underlying pathologic processes that can be documented by postmortem examination or in vivo by biomarkers. The diagnosis is not based on the clinical consequences of the disease (i.e., symptoms/signs) in this research framework, which shifts the definition of AD in living people from a syndromal to a biological construct (1). The “Framework” is based on research that confirms Alzheimer’s disease pathologic changes in the brain begin 15-20 years before the development of symptoms (2). The neuropathologic hallmarks of AD include: amyloid plaques, neurofibrillary tangles (NFTs), Glial responses, and synaptic and neuronal loss. This approach enables a more precise approach to interventional trials where specific pathways can be targeted in the disease process and in the appropriate people. It is hypothesized that during the preclinical period, 10-15 years prior to severe symptoms where fibrillar brain amyloid increases with minimal impact on cognition, that disease-modifying therapy can be most effective (3).

scholarly journals Aβ-Positivity Predicts Cognitive Decline but Cognition Also Predicts Progression to Aβ-Positivity

2019 ◽  
Author(s):  
Jeremy A. Elman ◽  
Matthew S. Panizzon ◽  
Daniel E. Gustavson ◽  
Carol E. Franz ◽  
Mark E. Sanderson ◽  
...  
Keyword(s):  
Cognitive Function ◽  
Cognitive Decline ◽  
Alzheimer’S Dementia ◽  
Cognitive Measures ◽  
Alzheimer's Dementia ◽  
Amyloid Aβ ◽  
Β Amyloid ◽  
Future Risk ◽  
Early Predictor

ABSTRACTIntroductionBiomarker positivity predicts cognitive decline and Alzheimer’s dementia. But what predicts biomarker positivity? We hypothesized that cognitive function and p-tau would predict progression from normal to abnormal levels of β-amyloid (Aβ).MethodsBaseline cognition in 292 non-demented, Aβ-negative Alzheimer’s Disease Neuroimaging Initiative (ADNI) participants was measured with two cognitive composites and compared between those that progressed to Aβ-positivity versus Aβ-stable. Follow-up analyses included continuous CSF Aβ and p-tau levels to examine subthreshold effects.ResultsContinuously measured baseline subthreshold Aβ and p-tau predicted progression to Aβ-positivity, but both baseline cognitive measures predicted progression to Aβ-positivity even after controlling for baseline biomarker levels.DiscussionCurrent Aβ thresholds may be ignoring relevant subthreshold pathology. Importantly, cognitive function can be an important early predictor of future risk, even earlier than the key biomarkers as currently measured. Moreover, A-/T+ individuals may still be on the AD pathway because p-tau also predicted progression to positivity.

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