ORIGINAL ARTICLE Past appendectomy may be related to early cognitive dysfunction in Parkinson’s disease Alexandra R. Gonçalves 1,2 & Alexandre Mendes 1,3 & Nuno Vila-Chã 1,2 & Joana Damásio 1,4 & Joana Fernandes 2 & Sara M. Cavaco 1,3 Received: 9 February 2020 /Accepted: 30 May 2020 # Fondazione Società Italiana di Neurologia 2020 Abstract Introduction The vermiform appendix is a potential site of initiation of Parkinson’s disease (PD) pathology. We hypothesized that the appendectomy earlier in life may alter the clinical expression of PD. Objective To explore the effects of appendectomy prior to onset of PD motor symptoms on patients’ symptoms, in particular on cognitive dysfunction. Methods Two hundred and sixty-two consecutive PD patients were asked about past history of appendectomy and underwent an evaluation, which included the Unified Parkinson’s Disease Rating Scale (UPDRS), Hoehn & Yahr scale (H&Y), Schwab & England Independence Scale (S&E), Dementia Rating Scale-2 (DRS-2), Apathy Evaluation Scale, Hospital Anxiety and Depression Scale, and Brief Smell Identification Test. Motor symptoms were evaluated in OFF and ON states. Non- parametric group comparisons and logistic regressions were used for data analyses. Results Thirty-one patients (11.8%) had history of appendectomy prior to PD onset. These patients had more severe motor symptoms (UPDRS-III and H&Y) and lower functional independence (S&E) in ON and had higher frequency of cognitive dysfunction (DRS-2 Initiation/Perseveration, Conceptualization, and Memory subscales) (p < 0.05). The association between history of appendectomy and cognitive dysfunction was evident only in patients with late onset PD (≥ 55 years) and with disease duration ≤ 5 years. History of appendectomy remained statistically associated with impairment on DRS-2 Conceptualization and Memory subscales, when demographic and clinical variables were considered. Conclusion History of appendectomy appears to alter the clinical expression of late onset PD, with early cognitive impairment, more severe motor symptoms in ON, and poorer functional independence under anti-parkinsonian medication. Keywords Parkinson’s disease . Cognitive dysfunction . Appendectomy Introduction Cognitive dysfunction is a common nonmotor manifes- tation of Parkinson’s disease (PD), with the prevalence of dementia estimated to be around 80% at 20 years of disease duration [1]. Even though some cognitive defi- cits may be present at the diagnosis of PD, significant cognitive decline usually develops later in the disease course. Recent literature [2, 3] has tried to integrate patterns of cognitive impairment with motor and non- motor phenotypes of PD [4, 5]. The neuropathological correlates of cognitive dysfunction in PD are still a matter of debate. There is evidence that cog- nitive dysfunction in PD is related to cortical Lewy pathology [ 6–10], though comorbid pathologies (e.g., amyloid-β plaques and tau neurofibrillary tangles) may also contribute to cognitive decline in PD [11–15]. Older age at PD onset is a known risk factor for early development of dementia [13, 16]. Clinicopathological studies suggest that dementia in the early stages of PD * Alexandra R. Gonçalves alexandra.r.goncalves@gmail.com 1 Department of Neurology, Centro Hospitalar Universitário do Porto, Largo Prof. Abel Salazar, 4099-001 Porto, Portugal 2 Faculty of Medicine, University of Porto, Porto, Portugal 3 Abel Salazar Biomedical Sciences Institute, University of Porto, Porto, Portugal 4 Institute for Molecular and Cell Biology (IBMC), University of Porto, Porto, Portugal Neurological Sciences https://doi.org/10.1007/s10072-020-04507-1