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Dal-Re R.,Clinical Research Program | Fauria K.,Clinical Research Program | Gramunt N.,Clinical Research Program | Molinuevo J.L.,Clinical Research Program | Molinuevo J.L.,Alzheimers Disease and Other Cognitive Disorders Unit
Journal of Alzheimer's Disease | Year: 2013

This study describes the main characteristics of ongoing observational studies on Alzheimer's disease (AD) to help identify any important research gaps. A search through the WHO International Clinical Trials Registry Platform and on the Primary Registries was conducted on 9 June 2012. The descriptors 'recruiting' or 'open' were used to describe a study's recruitment status. 62 studies are being conducted in 18 countries (Australia, Far-East, Middle-East, North America, and Western Europe). The US and France are involved in 55% of these studies. The studies aimed to recruit 20 to 10,000 participants, lasting 8 months to 24 years; 46% are case-control, whereas 44% are cohort studies; 60% and 34% are longitudinal and cross-sectional, respectively. The majority are sponsored by hospitals, universities, medical centers, or public health systems (63%), and are conducted in single centers (55%). 37 use imaging (MRI, PET, SPECT), 18 conduct lumbar puncture, 21 collect DNA and/or RNA, and 15 collect ApoE genotyping. 17 studies are medium-term prospective disease progression studies, the majority to assess mild cognitive impairment (MCI) or/and AD progression; only 3 are on cognitively normal older people at risk (2 studies, n = 180) or not (1 study, n < 200) of developing MCI. Observational studies are being conducted in few countries, with very few in low and middle-income countries where the majority of AD patients live. There is a remarkable interest in disease progression studies; however, longitudinal, long-term studies, on cognitively normal middle-age individuals, of key importance to try to fully understand the preclinical phase of AD, are lacking. © 2013 - IOS Press and the authors. All rights reserved. Source

Cummings J.L.,Cleveland Clinic | Dubois B.,Cleveland Clinic | Molinuevo J.L.,VU University Amsterdam | Scheltens P.,Alzheimers Disease and Other Cognitive Disorders Unit
Medical Clinics of North America | Year: 2013

Alzheimer-type biomarker changes are identifiable in asymptomatic and mildly symptomatic predementia phases of Alzheimer disease (AD) and AD dementia. The International Work Group (IWG) guidelines for diagnosis identify a unified spectrum of 3 phases. The classic clinical feature that indicates AD is an episodic memory defect of the amnestic type. IWG criteria require biomarker support for the diagnoses of AD at any clinical stage. Pathophysiologic and topographic biomarkers are recognized. These criteria are proposed to allow highly specific diagnosis of AD and assist in identifying patients for clinical trials of AD-related treatments and other types of AD research. © 2013. Source

Molinuevo J.L.,Alzheimers Disease and Other Cognitive Disorders Unit | Casado-Naranjo I.,Servicio de Neurologia
Journal of Alzheimer's Disease | Year: 2014

Epidemiological and clinical studies suggest that dementia patients aged ≥ 85 years are biologically different from those aged 65-84. This study aimed to assess whether patients (>85 years) have a distinct sociodemographic and clinical profile. Older patients had lower educational achievements, different carer relationships, and were more likely to take memantine/concomitant treatments and be institutionalized. Differences were observed with respect to concomitant disease/other risk factors (depression, dyslipidemia, cardiovascular disease, hypertension). Oldest patients had greater impairment (more severe Global Deterioration Scale stage, lower Mini-Mental State Examination scores). Greater concomitant drug use and younger carers associated with older patients suggest higher management and social costs. © 2014 - IOS Press and the authors. All rights reserved. Source

Molinuevo J.L.,Alzheimers Disease and Other Cognitive Disorders Unit | Molinuevo J.L.,Institute dInvestigacio Biomedica August Pi i Sunyer | Rami L.,Alzheimers Disease and Other Cognitive Disorders Unit | Rami L.,Institute dInvestigacio Biomedica August Pi i Sunyer
Medical Clinics of North America | Year: 2013

In 2007, new International Working Group research criteria introduced a new conceptualization of Alzheimer disease and created a framework for earlier diagnosis. There is increasing consensus to understand Alzheimer disease as a clinical-biologic entity, in which biomarkers, especially pathophysiologic markers revealing underlying pathology, represent the biologic counterpart of the diagnosis, and specific symptoms, such as episodic memory deficits, account for the clinical one. This article advances and moves forward on this. © 2013 Elsevier Inc. Source

Fortea J.,Alzheimers Disease and Other Cognitive Disorders Unit | Llado A.,Alzheimers Disease and Other Cognitive Disorders Unit | Bosch B.,Alzheimers Disease and Other Cognitive Disorders Unit | Antonell A.,Alzheimers Disease and Other Cognitive Disorders Unit | And 3 more authors.
Neurodegenerative Diseases | Year: 2011

Background/Aims: Familial Alzheimer's disease allows studies in the preclinical phases of the disease. We studied cerebrospinal fluid (CSF) amyloid β1-42 (Aβ1-42), total tau (t-tau) and phospho-tau181 (p-tau) levels in PSEN1 families and correlated the results with the genetic status, age and clinical stage. Methods: Thirteen subjects from 3 families with 2 PSEN1 mutations (L286P, M139T) were recruited from the genetic counseling program for familial dementia. Eight mutation carriers (MC) and 5 noncarriers (NC) underwent clinical and cognitive evaluations. CSF concentrations were obtained by ELISA methodology. Results: Symptomatic MC presented reduced CSF Aβ1-42 (mean = 175 pg/ml) and elevated t-tau (mean = 635 pg/ml) compared to controls, but not asymptomatic MC (mean = 684 and 255 pg/ml, respectively) at a median of -12.8 years from the predicted disease onset (adjusted age). Aβ1-42 levels presented an inverse correlation with the adjusted age (r = -1, p < 0. 01) in asymptomatic MC, but not in symptomatic MC or NC. t-tau presented a trend towards a negative correlation with Mini Mental State Examination (MMSE; r = -0.949, p = 0.051) in symptomatic MC but not in asymptomatic MC. In the whole group of MC, t-tau presented a significant positive correlation with Clinical Dementia Rating sum of boxes (r = 0.913, p = 0.002) and a negative correlation with MMSE (r = -0.946, p < 0.001). Conclusions: CSF Aβ1-42 levels correlate with time to disease onset in asymptomatic MC to reach floor levels when symptoms appear. CSF t-tau levels become elevated in symptomatic MC and correlate with clinical severity. These findings may suggest that the changes in Aβ1-42 precede t-tau elevation in PSEN1 MC. Copyright © 2011 S. Karger AG, Basel. Source

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