ASSESSMENT OF CLINICAL MEANINGFULNESS OF ENDPOINTS IN THE GENERATION PROGRAM BY THE INSIGHTS TO MODEL ALZHEIMER’S PROGRESSION IN REAL LIFE (IMAP) STUDY

2018 ◽  
pp. 1-5
Author(s):  
A. Graf ◽  
V. Risson ◽  
A. Gustavsson ◽  
V. Bezlyak ◽  
A. Caputo ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Large Scale ◽  
Real Life ◽  
Primary Objective ◽  
Cognitive Test ◽  
Clinical Dementia Rating ◽  
Life Study ◽  
Prospective Longitudinal ◽  
Clinical Meaningfulness

We are launching the Insights to Model Alzheimer’s Progression in Real Life study in parallel with the Alzheimer Prevention Initiative Generation Program. This is a 5-year, multinational, prospective, longitudinal, non-interventional cohort study that will collect data across the spectrum of Alzheimer’s disease. The primary objective is to assess the ability of the Alzheimer’s Prevention Initiative Cognitive Composite Test Score and Repeatable Battery for the Assessment of Neuropsychological Status to predict clinically meaningful outcomes such as diagnosis of mild cognitive impairment or dementia due to Alzheimer’s disease, and change in Clinical Dementia Rating – Global Score. This study is the first large-scale, prospective effort to establish the clinical meaningfulness of cognitive test scores that track longitudinal decline in preclinical Alzheimer’s disease. This study is also expected to contribute to our understanding of the relationships among outcomes in different stages of Alzheimer’s disease as well as models of individual trajectories during the course of the disease.

scholarly journals The Differential Diagnosis of Alzheimer's Disease: Conceptual and Methodological Issues

1986 ◽  
Vol 13 (S4) ◽  
pp. 424-426 ◽  
Author(s):  
Mary C. Tierney ◽  
David W. Reid ◽  
Maria L. Zorzitto ◽  
W. Gary Snow ◽  
Rory H. Fisher ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Large Scale ◽  
Methodological Issues ◽  
Normal Individuals ◽  
Comparison Groups ◽  
Assessment Procedures ◽  
Prospective Longitudinal ◽  
Insufficient Knowledge

Abstract:The study of Alzheimer's disease is hampered by insufficient knowledge of its cause. It can best be described as a syndrome whose clinical and pathological features, and their associations over time, need to be more carefully examined. Issues which impede our understanding of this syndrome include the lack of: (a) a singular “gold standard” for its identification; (b) longitudinal studies with appropriate comparison groups and neuropathological follow-up; and (c) standardized multifaceted clinical assessment procedures. Our awareness of the significance of these issues has led us to undertake a large-scale prospective, longitudinal investigation of 399 dementing and normal individuals at Sunnybrook Medical Centre. As a result of problems identified, it is proposed that research efforts across various Canadian centres be coordinated to best utilize available resources and expertise.

scholarly journals Neuropsychiatric symptoms and executive function impairments in Alzheimer’s disease and vascular dementia: The role of subcortical circuits

2019 ◽  
Vol 13 (3) ◽  
pp. 293-298 ◽  
Author(s):  
Chan Tiel ◽  
Felipe Kenji Sudo ◽  
Ana Beatriz Calmon
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Executive Function ◽  
Vascular Dementia ◽  
Neuropsychiatric Symptoms ◽  
Vascular Lesions ◽  
Cognitive Test ◽  
Pathophysiological Mechanism ◽  
Clinical Dementia Rating

ABSTRACT Neuropsychiatric symptoms (NPS) in dementia are prevalent, under-recognized and little studied regarding their pathophysiological aspects. The pathophysiological mechanism, as well as the possible role of vascular lesions in the genesis of these symptoms, are still matters of debate. Objective: to describe and compare the prevalence and severity of NPS in subjects with Alzheimer's disease (AD) and vascular dementia (VaD). Methods: a cross-sectional study involving 82 outpatients, divided into two groups (AD × VaD), was conducted. Patients were submitted to the Cambridge Cognitive Test (CAMCOG), the Clock Drawing Test (CLOX 1 and 2), the Neuropsychiatric Inventory (NPI) and the Clinical Dementia Rating (CDR) scale. Neuroimaging was scored using the de Leon and Fazekas scales. Results: 90.8% of the patients had at least one neuropsychiatric symptom. There were statistical differences on the CLOX test and in the apathy symptoms between AD and VaD groups. Apathy and disinhibition proved more prevalent in patients with higher vascular load. Conclusion: apathy and impaired executive function may reflect vascular damage in subcortical circuits in dementia patients.

scholarly journals Impact of hearing loss and vestibular decline on cognition in Alzheimer’s disease: a prospective longitudinal study protocol (Gehoor, Evenwicht en Cognitie, GECkO)

BMJ Open ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. e039601
Author(s):  
Joyce Bosmans ◽  
Cathérine Jorissen ◽  
Patrick Cras ◽  
Angelique Van Ombergen ◽  
Sebastiaan Engelborghs ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Hearing Loss ◽  
Longitudinal Study ◽  
Study Protocol ◽  
Cognitive Test ◽  
Secondary Outcome ◽  
Prospective Longitudinal Study ◽  
Prospective Longitudinal ◽  
Mci Due To Ad

IntroductionDementia is a prevalent disease affecting a growing number of the ageing population. Alzheimer’s disease (AD) is the most common cause of dementia. Previous research investigated the link between hearing loss and cognition, and the effect of vestibular dysfunction on cognition. Hearing loss and, to a lesser extent, vestibular decline both result in a decreasing cognitive function. However, their interaction should not be underestimated. The aim of this study is to assess the effect of hearing loss, vestibular decline and their interaction on cognition in people suffering from mild cognitive impairment (MCI) and dementia due to AD (ADD).Methods and analysisWe designed a prospective longitudinal study to assess the effect of hearing loss and vestibular decline on cognition. A total of 100 cognitively impaired elderly (between 55 and 84 years of age), consisting of 60 patients with MCI due to AD and 40 patients with ADD will be included. The control group will consist of individuals with preserved cognition group-matched based on age, hearing level and vestibular function. A comprehensive assessment is performed at baseline, 12-month and 24-month follow-ups. The primary outcome measure is the change in the Repeatable Battery for the Assessment of Neuropsychological Status adjusted for Hearing-impaired individuals total score, a cognitive test battery assessing different cognitive domains. Secondary outcome measures include additional neuropsychological assessments, cortical auditory-evoked potentials, and evaluation of general and disease-specific health-related quality of life. Variables include cognitive, audiological and vestibular evaluation. Variance analyses will assess the effect of hearing loss and vestibular decline on cognition. More precisely, the link between hearing loss and non-spatial cognitive functioning, the effect of vestibular decline on spatial cognition and the impact of both factors on the rate of conversion from MCI due to AD to ADD will be investigated.Ethics and disseminationThe study protocol was approved by the ethical committee of the Antwerp University Hospital on 4 February 2019 with protocol number B300201938949. The findings will be disseminated through peer-reviewed publications and conference presentations.Trial registration numberClinicalTrials.gov Registry (NCT04385225).

scholarly journals Impact of coronary heart disease on cognitive decline in Alzheimer’s disease: a prospective longitudinal cohort study in primary care

2016 ◽  
Vol 67 (655) ◽  
pp. e111-e117 ◽  
Author(s):  
Markus Bleckwenn ◽  
Luca Kleineidam ◽  
Michael Wagner ◽  
Frank Jessen ◽  
Siegfried Weyerer ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Coronary Heart Disease ◽  
Cohort Study ◽  
Heart Disease ◽  
Cognitive Decline ◽  
Late Onset ◽  
Cardiovascular Prevention ◽  
Clinical Dementia Rating ◽  
Prospective Longitudinal

BackgroundArteriosclerotic disorders increase the risk of dementia. As they have common causes and risk factors, coronary heart disease (CHD) could influence the course of dementia.AimTo determine whether CHD increases the speed of cognitive decline in Alzheimer’s disease, and to discuss the potential for secondary cardiovascular prevention to modify this decline.Design and settingProspective multicentre cohort study in general practices in six cities in Germany.MethodParticipants were patients with probable mild-to-moderate Alzheimer’s dementia or mixed dementia (n = 118; mean age 85.6 [±3.4] years, range 80–96 years). The authors assessed the presence of CHD according to the family physicians’ diagnosis. Cognitive performance was measured during home visits for up to 3 years in intervals of 6 months, using Mini Mental State Examination (MMSE) and Clinical Dementia Rating Sum of Boxes (CDR-SoB). The authors also recorded whether patients died in the observation period.ResultsAt baseline, 65 patients (55%) had CHD and/or a heart condition following a myocardial infarction. The presence of CHD accelerated cognitive decline (MMSE, P<0.05) by about 66%, and reduced cognitive-functional ability (CDR-SoB, P<0.05) by about 83%, but had no impact on survival.ConclusionThe study shows that CHD has a significant influence on cognitive decline in older patients with late-onset dementia. The dementia process might therefore be positively influenced by cardiovascular prevention, and this possible effect should be further investigated.

Dehydroepiandrosterone (DHEA) and its Sulphate (DHEAS) in Alzheimer’s Disease

2020 ◽  
Vol 17 (2) ◽  
pp. 141-157 ◽  
Author(s):  
Dubravka S. Strac ◽  
Marcela Konjevod ◽  
Matea N. Perkovic ◽  
Lucija Tudor ◽  
Gordana N. Erjavec ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Large Scale ◽  
Therapeutic Potential ◽  
Relevant Literature ◽  
Comprehensive Overview ◽  
Brain Functions ◽  
Specific Effects ◽  
And Behavior

Background: Neurosteroids Dehydroepiandrosterone (DHEA) and Dehydroepiandrosterone Sulphate (DHEAS) are involved in many important brain functions, including neuronal plasticity and survival, cognition and behavior, demonstrating preventive and therapeutic potential in different neuropsychiatric and neurodegenerative disorders, including Alzheimer’s disease. Objective: The aim of the article was to provide a comprehensive overview of the literature on the involvement of DHEA and DHEAS in Alzheimer’s disease. Method: PubMed and MEDLINE databases were searched for relevant literature. The articles were selected considering their titles and abstracts. In the selected full texts, lists of references were searched manually for additional articles. Results: We performed a systematic review of the studies investigating the role of DHEA and DHEAS in various in vitro and animal models, as well as in patients with Alzheimer’s disease, and provided a comprehensive discussion on their potential preventive and therapeutic applications. Conclusion: Despite mixed results, the findings of various preclinical studies are generally supportive of the involvement of DHEA and DHEAS in the pathophysiology of Alzheimer’s disease, showing some promise for potential benefits of these neurosteroids in the prevention and treatment. However, so far small clinical trials brought little evidence to support their therapy in AD. Therefore, large-scale human studies are needed to elucidate the specific effects of DHEA and DHEAS and their mechanisms of action, prior to their applications in clinical practice.

Structural Changes in Thalamic Nuclei Across Prodromal and Clinical Alzheimer’s Disease

2021 ◽  
pp. 1-11
Author(s):  
Adam S. Bernstein ◽  
Steven Z. Rapcsak ◽  
Michael Hornberger ◽  
Manojkumar Saranathan ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Large Scale ◽  
Structural Changes ◽  
Thalamic Nuclei ◽  
Medial Temporal Lobes ◽  
Cognitive Changes ◽  
Temporal Lobes ◽  
Medial Geniculate ◽  
Healthy Control

Background: Increasing evidence suggests that thalamic nuclei may atrophy in Alzheimer’s disease (AD). We hypothesized that there will be significant atrophy of limbic thalamic nuclei associated with declining memory and cognition across the AD continuum. Objective: The objective of this work was to characterize volume differences in thalamic nuclei in subjects with early and late mild cognitive impairment (MCI) as well as AD when compared to healthy control (HC) subjects using a novel MRI-based thalamic segmentation technique (THOMAS). Methods: MPRAGE data from the ADNI database were used in this study (n = 540). Healthy control (n = 125), early MCI (n = 212), late MCI (n = 114), and AD subjects (n = 89) were selected, and their MRI data were parcellated to determine the volumes of 11 thalamic nuclei for each subject. Volumes across the different clinical subgroups were compared using ANCOVA. Results: There were significant differences in thalamic nuclei volumes between HC, late MCI, and AD subjects. The anteroventral, mediodorsal, pulvinar, medial geniculate, and centromedian nuclei were significantly smaller in subjects with late MCI and AD when compared to HC subjects. Furthermore, the mediodorsal, pulvinar, and medial geniculate nuclei were significantly smaller in early MCI when compared to HC subjects. Conclusion: This work highlights nucleus specific atrophy within the thalamus in subjects with early and late MCI and AD. This is consistent with the hypothesis that memory and cognitive changes in AD are mediated by damage to a large-scale integrated neural network that extends beyond the medial temporal lobes.

Prospective longitudinal study of depression and anosognosia in Alzheimer's disease

1997 ◽  
Vol 171 (1) ◽  
pp. 47-52 ◽  
Author(s):  
Sergio E. Starkstein ◽  
Erán Chemerinski ◽  
Liliana Sabe ◽  
Gabriela Kuzis ◽  
Gustavo Petracca ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Major Depression ◽  
Cognitive Status ◽  
Initial Evaluation ◽  
Consecutive Series ◽  
Psychiatric Interview ◽  
Prospective Longitudinal Study ◽  
Prospective Longitudinal

BackgroundThe aim was to examine the longitudinal evolution of depression and anosognosia in patients with probable Alzheimer's disease (AD).MethodSixty-two of a consecutive series of 116 AD patients that were examined with a structured psychiatric interview had a follow-up evaluation between one and two years after the initial evaluation.ResultsAt the initial evaluation 19% of the 62 patients had major depression, 34% had dysthymia, and 47% were not depressed. After a mean follow-up of 16 months, 58% of patients with major depression at the initial evaluation were still depressed, whereas only 28% of patients with initial dysthymia and 21% of the non-depressed patients were depressed at follow-up. During the follow-up period, all three groups showed similar declines in cognitive status and activities of daily living. At the initial evaluation, 39% of the patients had anosognosia, and there was a significant increment of anosognosia during the follow-up period.ConclusionsWhile dysthymia in AD is a brief emotional disorder, major depression is a longer-lasting mood change. Anosognosia is another prevalent disorder among AD patients, and increases with the progression of the illness.

scholarly journals Autoregulation of Cerebral Blood Flow to Changes in Arterial Pressure in Mild Alzheimer's Disease

2010 ◽  
Vol 30 (11) ◽  
pp. 1883-1889 ◽  
Author(s):  
Allyson R Zazulia ◽  
Tom O Videen ◽  
John C Morris ◽  
William J Powers
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Arterial Pressure ◽  
The Elderly ◽  
Local Defect ◽  
Clinical Dementia Rating ◽  
Positron Emission ◽  
Before And After

Studies in transgenic mice overexpressing amyloid precursor protein (APP) demonstrate impaired autoregulation of cerebral blood flow (CBF) to changes in arterial pressure and suggest that cerebrovascular dysfunction may be critically important in the development of pathological Alzheimer's disease (AD). Given the relevance of such a finding for guiding hypertension treatment in the elderly, we assessed autoregulation in individuals with AD. Twenty persons aged 75±6 years with very mild or mild symptomatic AD (Clinical Dementia Rating 0.5 or 1.0) underwent 15O-positron emission tomography (PET) CBF measurements before and after mean arterial pressure (MAP) was lowered from 107±13 to 92±9 mm Hg with intravenous nicardipine; 11C-PIB-PET imaging and magnetic resonance imaging (MRI) were also obtained. There were no significant differences in mean CBF before and after MAP reduction in the bilateral hemispheres (−0.9±5.2 mL per 100 g per minute, P=0.4, 95% confidence interval (CI)=−3.4 to 1.5), cortical borderzones (−1.9±5.0 mL per 100 g per minute, P=0.10, 95% CI=−4.3 to 0.4), regions of T2W-MRI-defined leukoaraiosis (−0.3±4.4 mL per 100 g per minute, P=0.85, 95% CI=−3.3 to 3.9), or regions of peak 11C-PIB uptake (−2.5±7.7 mL per 100 g per minute, P=0.30, 95% CI=−7.7 to 2.7). The absence of significant change in CBF with a 10 to 15 mm Hg reduction in MAP within the normal autoregulatory range demonstrates that there is neither a generalized nor local defect of autoregulation in AD.

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