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    Home » Cognitive Symptoms in Genetic Forms of Parkinson’s Disease May Help in Distinguishing the Various Types
    ABSTRACT & COMMENTARY

    Cognitive Symptoms in Genetic Forms of Parkinson’s Disease May Help in Distinguishing the Various Types

    May 1, 2020
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    Keywords

    Dementia

    Depression

    Genetics

    parkinson’s

    manifestations

    By Harini Sarva, MD

    Assistant Professor of Clinical Neurology, Weill Cornell Medical College

    Dr. Sarva reports no financial relationships relevant to this field of study.

    SYNOPSIS: This paper illustrates that, of the confirmed genetic forms of Parkinson’s disease, there are common cognitive and psychiatric features, thus adding to our knowledge of the clinical phenotype of these genetic forms.

    SOURCE: Piredda R, Desmarais P, Masellis M, Gasca-Salas C. Cognitive and psychiatric symptoms in genetically determined Parkinson’s disease: A systematic review. Eur J Neurol 2020;27:229-234.

    This systematic review assessed the cognitive and psychiatric manifestations of well-established Mendelian genetic forms of Parkinson’s disease (PD) as a result of the following mutations: SNCA, LRRK2, VPS35, PINK1, parkin, and DJ1. The first three are autosomal dominant and the last three are recessive.

    A literature search from January 1997 to April 2018 yielded 95 papers, which were reviewed further by the authors. Among the 151 SNCA carriers, the cognitive and psychiatric impairments were dependent on the mutation types, with triplication mutations having the greatest rates of dementia in comparison to missense and duplication mutations.

    Depression and visual hallucinations were the most common psychiatric manifestations among SNCA carriers. Among the 1,625 LRRK2 mutation carriers, frontal lobe deficits and depression were the most common cognitive and psychiatric features, respectively. When comparing LRRK2 carriers to idiopathic PD patients, LRRK2 carriers had less depression but similar levels of anxiety. Seven out of 24 VPS35 carriers had cognitive impairment, and depression was quite common among those studied. Twenty-five of 81 parkin carriers, who had complete neurocognitive testing, demonstrated only three with mild cognitive impairment or dementia. Sixty-five of 89 had psychiatric assessments, and half had at least one of the following: depression, impulse control disorders, or anxiety. Among eight DJ1 carriers two had dementia and four had anxiety. Of 24 patients with PINK1 mutations, 17 had cognitive assessments and of these, five had dementia. Thirteen of the 24 had depression.

    COMMENTARY

    In addition to the motor and demographic features of genetic forms of PD, cognitive and psychiatric features can aid in the treatment and prognostication of these patients. Approximately 2,000 patients with well-established genetic forms of PD demonstrated various levels of cognitive and psychiatric features. However, these features alone may not aid in diagnosis, since mild cognitive impairment, frontal lobe deficits, depression, and anxiety are common among nongenetic forms of PD.

    In addition, the studies had variable sizes, did not always use the same scales for cognitive and psychiatric measures, and did not always have populations with the same mutations. Among the SNCA mutation carriers, those with a triplication mutation were more likely to have dementia, but how different mutations among the other groups of genetic forms of PD contribute to cognitive or psychiatric manifestations is unclear.

    Another important consideration is the diverse pathophysiological processes that result from these mutations, which may play a role in the timing and degree of cognitive and psychiatric manifestations. Although these manifestations can give a clue to clinicians about the different forms of PD, the motor features and demographics all should be combined to formulate a diagnostic plan and guide genetic testing. Future studies with larger sample sizes using longitudinal formal neuropsychiatric batteries are needed to assess the cognitive and psychiatric changes that occur in genetic forms of PD.

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    Neurology Alert

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    Neurology Alert (Vol. 39, No. 9) - May 2020
    May 1, 2020

    Table Of Contents

    Special Report from the 2020 International Stroke Conference, Los Angeles

    Zilucoplan for Myasthenia Gravis

    Cognitive Symptoms in Genetic Forms of Parkinson’s Disease May Help in Distinguishing the Various Types

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    Financial Disclosure: Editor in Chief Matthew Fink, MD, Peer Reviewer M. Flint Beal, MD, Editorial Group Manager Leslie Coplin, Editor Jason Schneider, Executive Editor Shelly Morrow Mark, and Accreditations Director Amy M. Johnson, MSN, RN, CPN, report no financial relationships relevant to this field of study.

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