title: A profile of The Clinical Course of Cognition and Comorbidity in Mild Cognitive Impairment and Dementia Study (The 4C study): two complementary longitudinal, clinical cohorts in the Netherlands.
abstract: BACKGROUND
  Heterogeneous disease trajectories of mild cognitive impairment (MCI) and dementia are frequently encountered in clinical practice, but there is still insufficient knowledge to understand the reasons and mechanisms causing this heterogeneity. In addition to correlates of the disorder, patient characteristics such as their health status, social environment, comorbidities and frailty may contribute to variability in trajectories over time. The current paper outlines the study design and the study population of and provides an overview of the data collected in the Clinical Course of Cognition and Comorbidity in Mild Cognitive Impairment (4C-MCI cohort, n = 315) and Dementia (4C-Dementia cohort, n = 331) Study.
  
  
  METHODS
  The two complementary longitudinal cohorts part of the 4C study began enrolment in March 2010. Participants were prospectively recruited from three collaborating Dutch Alzheimer Centers, with three annual follow-up assessments after baseline. Extensive neuropsychological assessments, and detailed profiling of comorbidities, health and frailty at each follow up were the key features of the 4C study. As such, the 4C study was designed to study if and how patients' comorbidities and frailty are associated with the course of MCI and dementia measured with a comprehensive and multidimensional set of outcomes including cognition, daily functioning, quality of life, behavioral disturbances, caregiver burden, institutionalization and death and whether the effects of medical health and frailty differ between MCI and dementia stages of cognitive disorders.
  
  
  CONCLUSIONS
  Sampled in a clinical setting, the 4C study complements population-based studies on neurodegenerative disorders in terms of the type of assessment (e.g. comorbidity, frailty, and functional status were repeatedly assessed). The 4C study complements available clinical cohorts of MCI and dementia patients, because the exclusion criteria were kept to a minimum, to obtain a sample that is representative for the average patient visiting a memory clinic.
authors.affiliation: Radboud Institute of Health Sciences, Department of Geriatric Medicine & Radboudumc Alzheimer Centre, Radboud University Medical Center, PO Box 9109, (House post 925), 6500 HB, Nijmegen, The Netherlands.
authors.forename: Weiqi
authors.initials: W
authors.lastname: Liao
authors.affiliation: Alzheimer Centre Limburg, School for Mental Health & Neuroscience, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Renske E G
authors.initials: RE
authors.lastname: Hamel
authors.affiliation: Donders Institute for Brain, Cognition and Behaviour, Department of Geriatric Medicine & Radboudumc Alzheimer Centre, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Marcel G M
authors.initials: MG
authors.lastname: Olde Rikkert
authors.affiliation: Radboud Institute of Health Sciences, Department of Geriatric Medicine & Radboudumc Alzheimer Centre, Radboud University Medical Center, PO Box 9109, (House post 925), 6500 HB, Nijmegen, The Netherlands.
authors.forename: Saskia M
authors.initials: SM
authors.lastname: Oosterveld
authors.affiliation: Alzheimer Centre Limburg, School for Mental Health & Neuroscience, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Pauline
authors.initials: P
authors.lastname: Aalten
authors.affiliation: Alzheimer Centre Limburg, School for Mental Health & Neuroscience, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Frans R J
authors.initials: FR
authors.lastname: Verhey
authors.affiliation: Alzheimer Center & Department of Neurology, VU University Medical Center, Neuroscience Campus, Amsterdam, The Netherlands.
authors.forename: Philip
authors.initials: P
authors.lastname: Scheltens
authors.affiliation: Alzheimer Center & Department of Neurology, VU University Medical Center, Neuroscience Campus, Amsterdam, The Netherlands.
authors.forename: Nicole
authors.initials: N
authors.lastname: Sistermans
authors.affiliation: Alzheimer Center & Department of Neurology, VU University Medical Center, Neuroscience Campus, Amsterdam, The Netherlands.
authors.forename: Yolande A L
authors.initials: YA
authors.lastname: Pijnenburg
authors.affiliation: Alzheimer Center & Department of Neurology, Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Wiesje M
authors.initials: WM
authors.lastname: van der Flier
authors.affiliation: Alzheimer Centre Limburg, School for Mental Health & Neuroscience, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Inez H G B
authors.initials: IH
authors.lastname: Ramakers
authors.affiliation: Radboud Institute of Health Sciences, Department of Geriatric Medicine & Radboudumc Alzheimer Centre, Radboud University Medical Center, PO Box 9109, (House post 925), 6500 HB, Nijmegen, The Netherlands. rene.melis@radboudumc.nl.
authors.forename: René J F
authors.initials: RJ
authors.lastname: Melis
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D003071:Cognition / Q000502:physiology; D003072:Cognition Disorders / Q000453:epidemiology / Q000503:physiopathology*; D060825:Cognitive Dysfunction / Q000503:physiopathology*; D015897:Comorbidity; D003704:Dementia / Q000453:epidemiology / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008568:Memory / Q000502:physiology; D008875:Middle Aged; D009426:Netherlands; D009483:Neuropsychological Tests; D011788:Quality of Life
keywords: Cognition; Comorbidity; Dementia; Disease progression; Frailty; Mild Cognitive Impairment (MCI)