Objective: The Parkinson’s Families Project (PFP) is a large-scale cohort of early onset (symptom onset <45) and familial Parkinson’s disease (PD) patients. One aim of this study is to examine how genetic factors influence phenotype. We present baseline clinical data from this cohort and clinical features associated with cognitive outcomes.

Background: Early onset PD patients tend to have lower rates of dementia than late onset patients, although mild cognitive impairment may occur even in early PD. Evidence shows that genotype may influence cognition, and cognitive impairment in early onset and familial PD patients may be strongly genetically determined. In addition to genotypic features, identifying clinical features that are associated with cognitive impairment, such as motor subtype and onset age, will assist in patient stratification.

Methods: 250 patients have been recruited to date from hospitals across the UK, using a similar dataset and method to the Tracking Parkinson’s (PRoBaND) study. Cognitive outcomes were assessed in the Montreal Cognitive Assessment (MoCA). Patients were also classified as having normal, mild or severe cognitive impairment based on MDS Task Force Criteria for PD-MCI Level 1 criteria (abbreviated assessment). Using screening thresholds [1,2], mild cognitive impairment was defined as MoCA score between 21 and 25; severe cognitive impairment (dementia) as scores ≤ 20. Linear regression was used to assess variables associated with cognition. Clinical outcomes will be correlated with genetic variation.

Results: In the first 117 patients, 29.9% of patients met criteria for mild cognitive impairment, 8.6% patients met criteria for severe cognitive impairment and 61.5% patients had normal cognition. Cognitive impairment was significantly associated with older age of onset (p=0.004), motor symptom severity (p=0.003) and REM Sleep Behaviour Disorder (p=0.004) but not motor subtype in initial backwards linear regression analysis. Analysis of genetic data is underway and full results with rare Mendelian mutations and common risk variants will be reported.

Conclusions: Identification of rare and common genetic factors that influence phenotype will lead to identification of new drug targets, improved prediction of outcomes and earlier treatment in clinical practice.

References: 1.          Nasreddine Z, Phillips N, Bédirian V, et al. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc. 2005;53(4):695-699.

2.          Dalrymple-Alford JC, Macaskill MR, Nakas CT, et al. The MoCA: Well-suited screen for cognitive impairment in Parkinson disease. Neurology. 2010;75(1):1717-1725.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/cognitive-impairment-in-early-onset-and-familial-parkinsons-disease/