title: Alzheimer's disease.
abstract: Although the prevalence of dementia continues to increase worldwide, incidence in the western world might have decreased as a result of better vascular care and improved brain health. Alzheimer's disease, the most prevalent cause of dementia, is still defined by the combined presence of amyloid and tau, but researchers are gradually moving away from the simple assumption of linear causality as proposed in the original amyloid hypothesis. Age-related, protective, and disease-promoting factors probably interact with the core mechanisms of the disease. Amyloid β42, and tau proteins are established core cerebrospinal biomarkers; novel candidate biomarkers include amyloid β oligomers and synaptic markers. MRI and fluorodeoxyglucose PET are established imaging techniques for diagnosis of Alzheimer's disease. Amyloid PET is gaining traction in the clinical arena, but validity and cost-effectiveness remain to be established. Tau PET might offer new insights and be of great help in differential diagnosis and selection of patients for trials. In the search for understanding the disease mechanism and keys to treatment, research is moving increasingly into the earliest phase of disease. Preclinical Alzheimer's disease is defined as biomarker evidence of Alzheimer's pathological changes in cognitively healthy individuals. Patients with subjective cognitive decline have been identified as a useful population in whom to look for preclinical Alzheimer's disease. Moderately positive results for interventions targeting several lifestyle factors in non-demented elderly patients and moderately positive interim results for lowering amyloid in pre-dementia Alzheimer's disease suggest that, ultimately, there will be a future in which specific anti-Alzheimer's therapy will be combined with lifestyle interventions targeting general brain health to jointly combat the disease. In this Seminar, we discuss the main developments in Alzheimer's research.
authors.affiliation: Department of Neurology & Alzheimer Center, VU University Medical Center, Amsterdam, Netherlands. Electronic address: p.scheltens@vumc.nl.
authors.forename: Philip
authors.initials: P
authors.lastname: Scheltens
authors.affiliation: Clinical Neurochemistry Lab, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
authors.affiliation: German Center for Neurodegenerative diseases (DZNE), and Institute for Medical Biometry, Informatics and Epidemiology, University of Bonn, Bonn, Germany.
authors.forename: Monique M B
authors.initials: MM
authors.lastname: Breteler
authors.affiliation: VIB Center for the Biology of Disease, VIB-Leuven, Leuven, Belgium; KU Leuven Center for Human Genetics, LIND en Universitaire ziekenhuizen, Leuven, Belgium; Institute of Neurology, University College London, London, UK.
authors.forename: Bart
authors.initials: B
authors.lastname: de Strooper
authors.affiliation: University Hospitals and University of Geneva, Geneva, Switzerland; IRCCS Fatebenefratelli, Brescia, Italy.
authors.forename: Giovanni B
authors.initials: GB
authors.lastname: Frisoni
authors.affiliation: Warren Alpert Medical School, Brown University, Providence, RI, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Salloway
authors.affiliation: Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, Netherlands.
authors.forename: Wiesje Maria
authors.initials: WM
authors.lastname: Van der Flier
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000175:diagnosis / Q000378:metabolism / Q000517:prevention & control / Q000523:psychology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D003071:Cognition; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000008:administration & dosage; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography / Q000379:methods; D019275:Radiopharmaceuticals / Q000008:administration & dosage; D040242:Risk Reduction Behavior; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D019275:Radiopharmaceuticals; D016875:tau Proteins; D019788:Fluorodeoxyglucose F18