At the time of clinical diagnosis, patients with Parkinson's disease already have a wide range of motor and non-motor features that affect their daily functioning. However, the temporal sequence of occurrence of these features remains largely unknown. We studied trajectories of daily functioning and motor and non-motor features in the 23 years preceding Parkinson's disease diagnosis by performing a nested case-control study within the prospective Rotterdam study. Between 1990 and 2013, we repeatedly performed standardized assessments of daily functioning (Stanford Health Assessment Questionnaire, Lawton Instrumental Activities of Daily Living Scale), potential prediagnostic motor (hypo- and bradykinesia, tremor, rigidity, postural imbalance, postural abnormalities) and non-motor features of Parkinson's disease, including cognition (Mini-Mental State Examination, Stroop Test, Letter-Digit-Substitution Test, Word Fluency Test), mood (Center for Epidemiological Studies-Depression Scale, Hamilton Anxiety and Depression Scale), and autonomic function (blood pressure, laxative use). In addition, the cohort was followed-up for the onset of clinical Parkinson's disease using several overlapping modalities, including repeated in-person examinations, as well as complete access to medical records and specialist letters of study participants. During follow-up, 109 individuals were diagnosed with Parkinson's disease, and each case was matched to 10 controls based on age and sex (total n=1199). Subsequently, we compared prediagnostic trajectories of daily functioning and other features between Parkinson's disease cases and controls. From 7 years before diagnosis onwards, prediagnostic Parkinson's disease cases more commonly had problems in instrumental activities of daily functioning, and more frequently showed signs of movement poverty and slowness, tremor and subtle cognitive deficits. In the past 5 years, Parkinson's disease cases developed additional motor features (postural imbalance, rigidity, and postural abnormalities) and increasingly reported problems in basic daily activities. Parkinson's disease cases also increasingly reported anxiety symptoms, depressive symptoms, and use of laxatives throughout study follow-up, although differences with controls only became statistically significant in the last years before diagnosis. In conclusion, in patients with prediagnostic Parkinson's disease, impairments in instrumental daily activities, which require both motor and non-motor skills, pre-date difficulties in more physically oriented daily activities.

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Keywords Activities of daily living, Parkinson's disease, Prediagnostic study
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Journal Brain: a journal of neurology
Darweesh, S.K.L, Verlinden, V.J.A, Stricker, B.H.Ch, Hofman, A, Koudstaal, P.J, & Ikram, M.K. (2017). Trajectories of prediagnostic functioning in Parkinson's disease. Brain: a journal of neurology, 140(2), 429–441. doi:10.1093/brain/aww291