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Systematic review of genetic variants associated with cognitive impairment and depressive symptoms in Parkinson’s disease

Published online by Cambridge University Press:  27 August 2019

Tyrra D’Souza  and
Anto P. Rajkumar Open the ORCID record for Anto P. Rajkumar [Opens in a new window]
Tyrra D’Souza
Affiliation:
Department of Old Age Psychiatry, Institute of Psychiatry, Psychology, & Neuroscience, King’s College London, 16, De Crespigny Park, London-SE5 8AF, UK
Anto P. Rajkumar*
Affiliation:
Department of Old Age Psychiatry, Institute of Psychiatry, Psychology, & Neuroscience, King’s College London, 16, De Crespigny Park, London-SE5 8AF, UK Mental Health of Older Adults and Dementia Clinical Academic Group, South London and Maudsley NHS foundation Trust, 115, Denmark Hill, London-SE5 8AQ, UK
*
Author for correspondence: Anto P. Rajkumar, E-mail: [email protected]
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Abstract

Objective:

Cognitive impairment and depression are among the most prevalent and most disabling non-motor symptoms in Parkinson’s disease (PD). The genetic factors that are associated with these symptoms remain uncertain. This systematic review aims to summarise the prevailing evidence from all genetic association studies investigating the genetic variants associated with cognitive impairment and depressive symptoms in people with PD.

Method:

A systematic review using five online databases: PubMed, PsycINFO, CINAHL, EMBASE and OpenGrey (PROSPERO protocol: CRD42017067431). We completed the quality assessment using the Q-Genie tool.

Results:

2353 articles were screened, and 43 articles were found to be eligible to be included. A meta-analysis of studies investigating LRRK2 rs34637584 confirmed that the minor allele carriers had significantly less cognitive impairment (p = 0.015). Further meta-analyses showed that GBA variants rs76763715 (p < 0.001) and rs421016 (p = 0.001) were significantly associated with more cognitive impairment in people with PD. Minor alleles of GBA variants rs76763715, rs421016, rs387906315 and rs80356773 were associated with more depressive symptoms in PD. Moreover, APOE ε4 allele has been associated with more cognitive impairment in PD. BDNF (rs6265) and CRY1 (rs2287161) variants have been associated with more depressive symptoms in people with PD.

Conclusions:

PD carriers of GBA variants are at high risk for cognitive decline and depression. Screening for these variants may facilitate early identification and effective management of these non-motor symptoms. The molecular mechanisms underlying favourable cognitive functioning in LRRK2 rs34637584 variant carriers warrant further investigation.

Keywords

cognitiondepressionParkinson’s diseasesystematic review
Type
Review Article
Information
Acta Neuropsychiatrica , Volume 32 , Issue 1 , February 2020 , pp. 10 - 22
Copyright
© Scandinavian College of Neuropsychopharmacology 2019 

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References

Aarsland, D and Kurz, MW (2010) The epidemiology of dementia associated with Parkinson’s disease. Brain Pathology 20, 633–639.CrossRefGoogle ScholarPubMed
Alcalay, RN, Caccappolo, E, Mejia-Santana, H, Tang, M, Rosado, L, Orbe Reilly, M, Ruiz, D, Ross, B, Verbitsky, M, Kisselev, S, Louis, E, Comella, C, Colcher, A, Jennings, D, Nance, M, Bressman, S, Scott, WK, Tanner, C, Mickel, S, Andrews, H, Waters, C, Fahn, S, Cote, L, Frucht, S, Ford, B, Rezak, M, Novak, K, Friedman, JH, Pfeiffer, R, Marsh, L, Hiner, B, Siderowf, A, Payami, H, Molho, E, Factor, S, Ottman, R, Clark, LN and Marder, K (2012) Cognitive performance of GBA mutation carriers with early-onset PD: the CORE-PD study. Neurology 78, 1434–1440.CrossRefGoogle ScholarPubMed
Alcalay, RN, Mejia-Santana, H, Mirelman, A, Saunders-Pullman, R, Raymond, D, Palmese, C, Caccappolo, E, Ozelius, L, Orr-Urtreger, A, Clark, L, Giladi, N, Bressman, S, Marder, K and LRRK2 Ashkenazi Jewish Consortium (2015) Neuropsychological performance in LRRK2 G2019S carriers with Parkinson’s disease. Parkinsonism & Related Disorders 21, 106–110.CrossRefGoogle ScholarPubMed
Alcalay, RN, Mejia-Santana, H, Tang, MX, Rakitin, B, Rosado, L, Ross, B, Verbitsky, M, Kisselev, S, Louis, ED, Comella, CL, Colcher, A, Jennings, D, Nance, MA, Bressman, S, Scott, WK, Tanner, C, Mickel, SF, Andrews, HF, Waters, CH, Fahn, S, Cote, LJ, Frucht, SJ, Ford, B, Rezak, M, Novak, K, Friedman, JH, Pfeiffer, R, Marsh, L, Hiner, B, Siderowf, A, Ottman, R, Clark, LN, Marder, KS and Caccappolo, E (2010) Self-report of cognitive impairment and mini-mental state examination performance in PRKN, LRRK2, and GBA carriers with early onset Parkinson’s disease. Journal of Clinical and Experimental Neuropsychology 32, 775–779.CrossRefGoogle ScholarPubMed
Altmann, V, Schumacher-Schuh, AF, Rieck, M, Callegari-Jacques, SM, Rieder, CR and Hutz, MH (2016) Val66Met BDNF polymorphism is associated with Parkinson’s disease cognitive impairment. Neuroscience Letters 615, 88–91.CrossRefGoogle ScholarPubMed
Anguelova, M, Benkelfat, C and Turecki, G (2003) A systematic review of association studies investigating genes coding for serotonin receptors and the serotonin transporter: II. Suicidal behavior. Molecular Psychiatry 8, 646–653.CrossRefGoogle ScholarPubMed
Arabia, G, Grossardt, BR, Geda, YE, Carlin, JM, Bower, JH, Ahlskog, JE, Maraganore, DM and Rocca, WA (2007) Increased risk of depressive and anxiety disorders in relatives of patients with Parkinson disease. Archives of General Psychiatry 64, 1385–1392.CrossRefGoogle ScholarPubMed
Barone, P, Erro, R and Picillo, M (2017) Quality of life and nonmotor symptoms in Parkinson’s disease. International Review of Neurobiology 133, 499–516.CrossRefGoogle ScholarPubMed
Barrero, FJ, Ampuero, I, Morales, B, Vives, F, De Dios Luna Del Castillo, J, Hoenicka, J and García Yébenes, J (2005) Depression in Parkinson’s disease is related to a genetic polymorphism of the cannabinoid receptor gene (CNR1). The Pharmacogenomics Journal 5, 135–141.CrossRefGoogle Scholar
Barrett, MJ, Koeppel, AF, Flanigan, JL, Turner, SD and Worrall, BB (2016) Investigation of genetic variants associated with Alzheimer disease in Parkinson disease cognition. Journal of Parkinson's Disease 6, 119–124.CrossRefGoogle ScholarPubMed
Beck, AT, Steer, RA and Brown, GK (1996) Beck Depression Inventory-II, vol 78,. San Antonio, TX: Psychological Corporation, pp. 490–498.Google Scholar
Belarbi, S, Hecham, N, Lesage, S, Kediha, MI, Smail, N, Benhassine, T, Ysmail-Dahlouk, F, Lohman, E, Benhabyles, B, Hamadouche, T, Assami, S, Brice, A and Tazir, M (2010) LRRK2 G2019S mutation in Parkinson’s disease: a neuropsychological and neuropsychiatric study in a large Algerian cohort. Parkinsonism & Related Disorders 16, 676–679.CrossRefGoogle Scholar
Ben Sassi, S, Nabli, F, Hentati, E, Nahdi, H, Trabelsi, M, Ben Ayed, H, Amouri, R, Duda, JE, Farrer, MJ and Hentati, F (2012) Cognitive dysfunction in Tunisian LRRK2 associated Parkinson’s disease. Parkinsonism & Related Disorders 18, 243–246.CrossRefGoogle ScholarPubMed
Border, R, Johnson, EC, Evans, LM, Smolen, A, Berley, N, Sullivan, PF and Keller, MC (2019) No support for historical candidate gene or candidate gene-by-interaction hypotheses for major depression across multiple large samples. The American Journal of Psychiatry 176, 376–387.CrossRefGoogle ScholarPubMed
Brockmann, K, Srulijes, K, Hauser, AK, Schulte, C, Csoti, I, Gasser, T and Berg, D (2011) GBA-associated PD presents with nonmotor characteristics. Neurology 77, 276–280.CrossRefGoogle ScholarPubMed
Brockmann, K, Srulijes, K, Pflederer, S, Hauser, AK, Schulte, C, Maetzler, W, Gasser, T and Berg, D (2015) GBA-associated Parkinson’s disease: reduced survival and more rapid progression in a prospective longitudinal study. Movement Disorders 30, 407–411.CrossRefGoogle Scholar
Burn, DJ, Tiangyou, W, Allcock, LM, Davison, J and Chinnery, PF (2006) Allelic variation of a functional polymorphism in the serotonin transporter gene and depression in Parkinson’s disease. Parkinsonism & Related Disorders 12, 139–141.CrossRefGoogle ScholarPubMed
Cagni, FC, Campelo, C, Coimbra, DG, Barbosa, MR, Junior, LGO, Neto, ABS, Ribeiro, AM, Júnior, COG, Gomes de Andrade, T and Silva, RH (2017) Association of BDNF Val66MET Polymorphism with Parkinson’s disease and depression and anxiety symptoms. The Journal of Neuropsychiatry and Clinical Neurosciences 29, 142–147.CrossRefGoogle ScholarPubMed
Chahine, LM, Urbe, L, Caspell-Garcia, C, Aarsland, D, Alcalay, R, Barone, P, Burn, D, Espay, AJ, Hamilton, JL, Hawkins, KA, Lasch, S, Leverenz, JB, Litvan, I, Richard, I, Siderowf, A, Coffey, CS, Simuni, T, Weintraub, D and Parkinson’s Progression Markers Initiative (2018) Cognition among individuals along a spectrum of increased risk for Parkinson’s disease. PLoS One 13, e0201964.CrossRefGoogle ScholarPubMed
Clark, LN, Kartsaklis, LA, Wolf Gilbert, R, Dorado, B, Ross, BM, Kisselev, S, Verbitsky, M, Mejia-Santana, H, Cote, LJ, Andrews, H, Vonsattel, JP, Fahn, S, Mayeux, R, Honig, LS and Marder, K (2009) Association of glucocerebrosidase mutations with dementia with Lewy bodies. Archives of Neurology 66, 578–583.CrossRefGoogle ScholarPubMed
Cummings, JL (1991) Depression and Parkinson’s disease: a review. The American Journal of Psychiatry 149, 443–454.Google Scholar
Da Silva, CP, de M Abreu, G, Cabello Acero, PH, Campos, MJ, Pereira, JS, De A Ramos, SR, Nascimento, CM, Voigt, DD, Rosso, AL, Araujo Leite, MA, Vasconcellos, LFR, Nicaretta, DH, Della Coletta, MV, da Silva, DJ, Gonçalves, AP, Dos Santos, JM, Calassara, V, Valença, DCT, de M Martins, CJ, Santos-Rebouças, CB and Pimentel, MMG (2017) Clinical profiles associated with LRRK2 and GBA mutations in Brazilians with Parkinson’s disease. Journal of the Neurological Sciences 381, 160–164.CrossRefGoogle ScholarPubMed
Dan, X, Wang, C, Zhang, J, Gu, Z, Zhou, Y, Ma, J and Chan, P (2016) Association between common genetic risk variants and depression in Parkinson’s disease: a dPD study in Chinese. Parkinsonism & Related Disorders 33, 122–126.CrossRefGoogle ScholarPubMed
Davis, MY, Johnson, CO, Leverenz, JB, Weintraub, D, Trojanowski, JQ, Chen-Plotkin, A, Van Deerlin, VM, Quinn, JF, Chung, KA, Peterson-Hiller, AL, Rosenthal, LS, Dawson, TM, Albert, MS, Goldman, JG, Stebbins, GT, Bernard, B, Wszolek, ZK, Ross, OA, Dickson, DW, Eidelberg, D, Mattis, PJ, Niethammer, M, Yearout, D, Hu, SC, Cholerton, BA, Smith, M, Mata, IF, Montine, TJ, Edwards, KL and Zabetian, CP (2016) Association of GBA mutations and the E326K polymorphism with motor and cognitive progression in Parkinson disease. JAMA Neurology 73, 1217–1224.CrossRefGoogle ScholarPubMed
Dissanayaka, NNW, Silburn, PA, O’sullivan, JD and Mellick, GD (2009) Serotonin and dopamine transporter genes do not influence depression in Parkinson’s disease. Movement Disorders 24, 111–115.CrossRefGoogle Scholar
Estanga, A, Rodriguez-Oroz, MC, Ruiz-Martinez, J, Barandiaran, M, Gorostidi, A, Bergareche, A, Mondragon, E, Lopez de Munain, A and Marti-Masso, JF (2014) Cognitive dysfunction in Parkinson’s disease related to the R1441G mutation in LRRK2. Parkinsonism & Related Disorders 20, 1097–1100.CrossRefGoogle ScholarPubMed
Folstein, MF, Folstein, SE and Mchugh, PR (1975) ‘Mini-mental state’. A practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research 12, 189–198.CrossRefGoogle Scholar
Gaig, C, Vilas, D, Infante, J, Sierra, M, Garcia-Gorostiaga, I, Buongiorno, M, Schmidt, A, van der Vegt, J, Siebner, H, Buhmann, C, Lencer, R, Kumar, KR, Lohmann, K, Hagenah, J and Klein, C (2014) Nonmotor symptoms in LRRK2 G2019S associated Parkinson’s disease. PLoS One 9, e108982.CrossRefGoogle ScholarPubMed
Gan-Or, Z, Amshalom, I, Kilarski, LL, Bar-Shira, A, Gana-Weisz, M, Mirelman, A, Marder, K, Bressman, S, Giladi, N and Orr-Urtreger, A (2015) Differential effects of severe vs mild GBA mutations on Parkinson disease. Neurology 84, 880–887.CrossRefGoogle ScholarPubMed
Gilsbach, BK and Kortholt, A (2014) Structural biology of the LRRK2 GTPase and kinase domains: implications for regulation. Frontiers in Molecular Neuroscience 7, 32.CrossRefGoogle ScholarPubMed
Gomperts, SN, Locascio, JJ, Rentz, D, Santarlasci, A, Marquie, M, Johnson, KA and Growdon, JH (2013) Amyloid is linked to cognitive decline in patients with Parkinson disease without dementia. Neurology 80, 85–91.CrossRefGoogle ScholarPubMed
Goris, A, Williams-Gray, CH, Clark, GR, Foltynie, T, Lewis, SJ, Brown, J, Ban, M, Spillantini, MG, Compston, A, Burn, DJ, Chinnery, PF, Barker, RA and Sawcer, SJ (2007) Tau and alpha-synuclein in susceptibility to, and dementia in, Parkinson’s disease. Annals of Neurology 62, 145–153.CrossRefGoogle ScholarPubMed
Henry, AG, Aghamohammadzadeh, S, Samaroo, H, Chen, Y, Mou, K, Needle, E and Hirst, WD (2015) Pathogenic LRRK2 mutations, through increased kinase activity, produce enlarged lysosomes with reduced degradative capacity and increase ATP13A2 expression. Human Molecular Genetics 24, 6013–6028.CrossRefGoogle ScholarPubMed
Hong, JH, Kim, YK, Park, JS, Lee, JE, Oh, MS, Chung, EJ, Kim, JY, Sung, YH, Lyoo, CH, Lee, JH, Kwon, DY, Kim, HS, Shin, HW, Park, SA, Park, IS, Kim, JS, Lee, PH, Koh, SB, Baik, JS, Kim, SJ, Ma, HI, Kim, JW and Kim, YJ (2017) Lack of association between LRRK2 G2385R and cognitive dysfunction in Korean patients with Parkinson’s disease. Journal of Clinical Neuroscience 36, 108–113.CrossRefGoogle ScholarPubMed
Hua, P, Liu, W, Kuo, SH, Zhao, Y, Chen, L, Zhang, N, Wang, C, Guo, S, Wang, L, Xiao, H, Kwan, JY and Wu, T (2012) Association of Tef polymorphism with depression in Parkinson disease. Movement Disorders 27, 1694–1697.CrossRefGoogle ScholarPubMed
Irwin, DJ, White, MT, Toledo, JB, Xie, SX, Robinson, JL, Van Deerlin, V, Lee, VM, Leverenz, JB, Montine, TJ, Duda, JE, Hurtig, HI and Trojanowski, JQ (2012) Neuropathologic substrates of Parkinson disease dementia. Annals of Neurology 72, 587–598.CrossRefGoogle ScholarPubMed
Kalia, LV, Lang, AE, Hazrati, LN, Fujioka, S, Wszolek, ZK, Dickson, DW, Ross, OA, Van Deerlin, VM, Trojanowski, JQ, Hurtig, HI, Alcalay, RN, Marder, KS, Clark, LN, Gaig, C, Tolosa, E, Ruiz-Martínez, J, Marti-Masso, JF, Ferrer, I, López de Munain, A, Goldman, SM, Schüle, B, Langston, JW, Aasly, JO, Giordana, MT, Bonifati, V, Puschmann, A, Canesi, M, Pezzoli, G, Maues De Paula, A, Hasegawa, K, Duyckaerts, C, Brice, A, Stoessl, AJ and Marras, C (2015) Clinical correlations with Lewy body pathology in LRRK2-related Parkinson disease. JAMA Neurology 72, 100–105.CrossRefGoogle ScholarPubMed
Kasten, M, Kertelge, L, Tadic, V, Bruggemann, N, Schmidt, A, Van Der Vegt, J, Siebner, H, Buhmann, C, Lencer, R, Kumar, KR, Lohmann, K, Hagenah, J and Klein, C (2012) Depression and quality of life in monogenic compared to idiopathic, early-onset Parkinson’s disease. Movement Disorders 27, 754–759.CrossRefGoogle ScholarPubMed
Kurz, MW, Dekomien, G, Nilsen, OB, Larsen, JP, Aarsland, D and Alves, G (2009) APOE alleles in Parkinson disease and their relationship to cognitive decline: a population-based, longitudinal study. Journal of Geriatric Psychiatry and Neurology 22, 166–170.CrossRefGoogle ScholarPubMed
Li, JQ, Tan, L and Yu, JT (2014) The role of the LRRK2 gene in Parkinsonism. Molecular Neurodegeneration 9, 47.CrossRefGoogle ScholarPubMed
Liu, G, Locascio, JJ, Corvol, JC, Boot, B, Liao, Z, Page, K, Franco, D, Burke, K, Jansen, IE, Trisini-Lipsanopoulos, A, Winder-Rhodes, S, Tanner, CM, Lang, AE, Eberly, S, Elbaz, A, Brice, A, Mangone, G, Ravina, B, Shoulson, I, Cormier-Dequaire, F, Heutink, P, van Hilten, JJ, Barker, RA, Williams-Gray, CH, Marinus, J, Scherzer, CR, HBS, CamPaIGN, PICNICS, PROPARK, PSG, DIGPD and PDBP (2017) Prediction of cognition in Parkinson’s disease with a clinical-genetic score: a longitudinal analysis of nine cohorts. The Lancet Neurology 16, 620–629.CrossRefGoogle ScholarPubMed
Malec-Litwinowicz, M, Rudzinska, M, Szubiga, M, Michalski, M, Tomaszewski, T and Szczudlik, A (2014) Cognitive impairment in carriers of glucocerebrosidase gene mutation in Parkinson disease patients. Neurology and Neurosurgery of Poland 48, 258–261.Google ScholarPubMed
Marsh, L (2000) Neuropsychiatric aspects of Parkinson’s disease. Psychosomatics 41, 15–23.CrossRefGoogle ScholarPubMed
Martinez-Martin, P, Gil-Nagel, A, Gracia, LM, Gomez, JB, Martinez-Sarries, J and Bermejo, F (1994) Unified Parkinson’s Disease Rating Scale characteristics and structure. The Cooperative Multicentric Group. Movement Disorders 9, 76–83.CrossRefGoogle ScholarPubMed
Mata, IF, Johnson, CO, Leverenz, JB, Weintraub, D, Trojanowski, JQ, Van Deerlin, VM, Ritz, B, Rausch, R, Factor, SA, Wood-Siverio, C, Quinn, JF, Chung, KA, Peterson-Hiller, AL, Espay, AJ, Revilla, FJ, Devoto, J, Yearout, D, Hu, SC, Cholerton, BA, Montine, TJ, Edwards, KL and Zabetian, CP (2017) Large-scale exploratory genetic analysis of cognitive impairment in Parkinson’s disease. Neurobiology of Aging 56, 211 e1–211 e7.CrossRefGoogle ScholarPubMed
Mata, IF, Leverenz, JB, Weintraub, D, Trojanowski, JQ, Chen-Plotkin, A, Van Deerlin, VM, Ritz, B, Rausch, R, Factor, SA, Wood-Siverio, C, Quinn, JF, Chung, KA, Peterson-Hiller, AL, Goldman, JG, Stebbins, GT, Bernard, B, Espay, AJ, Revilla, FJ, Devoto, J, Rosenthal, LS, Dawson, TM, Albert, MS, Tsuang, D, Huston, H, Yearout, D, Hu, SC, Cholerton, BA, Montine, TJ, Edwards, KL and Zabetian, CP (2016) GBA Variants are associated with a distinct pattern of cognitive deficits in Parkinson’s disease. Movement Disorders 31, 95–102.CrossRefGoogle ScholarPubMed
Mata, IF, Leverenz, JB, Weintraub, D, Trojanowski, JQ, Hurtig, HI, Van Deerlin, VM, Ritz, B, Rausch, R, Rhodes, SL, Factor, SA, Wood-Siverio, C, Quinn, JF, Chung, KA, Peterson, AL, Espay, AJ, Revilla, FJ, Devoto, J, Hu, SC, Cholerton, BA, Wan, JY, Montine, TJ, Edwards, KL and Zabetian, CP (2014) APOE, MAPT, and SNCA genes and cognitive performance in Parkinson disease. JAMA Neurology 71, 1405–1412.CrossRefGoogle ScholarPubMed
Menza, MA, Palermo, B, Dipaola, R, Sage, JI and Ricketts, MH (1999) Depression and anxiety in Parkinson’s disease: possible effect of genetic variation in the serotonin transporter. Journal of Geriatric Psychiatry and Neurology 12, 49–52.CrossRefGoogle ScholarPubMed
Morley, JF, Xie, SX, Hurtig, HI, Stern, MB, Colcher, A, Horn, S, Dahodwala, N, Duda, JE, Weintraub, D, Chen-Plotkin, AS, Van Deerlin, V, Falcone, D and Siderowf, A (2012) Genetic influences on cognitive decline in Parkinson’s disease. Movement Disorders 27, 512–518.CrossRefGoogle ScholarPubMed
Muslimovic, D, Post, B, Speelman, JD and Schmand, B (2005) Cognitive profile of patients with newly diagnosed Parkinson disease. Neurology 65, 1239–1245.CrossRefGoogle ScholarPubMed
Neumann, J, Bras, J, Deas, E, O’sullivan, SS, Parkkinen, L, Lachmann, RH, Li, A, Holton, J, Guerreiro, R, Paudel, R, Segarane, B, Singleton, A, Lees, A, Hardy, J, Houlden, H, Revesz, T and Wood, NW (2009) Glucocerebrosidase mutations in clinical and pathologically proven Parkinson’s disease. Brain 132, 1783–1794.CrossRefGoogle ScholarPubMed
Nombela, C, Rowe, JB, Winder-Rhodes, SE, Hampshire, A, Owen, AM, Breen, DP, Duncan, GW, Khoo, TK, Yarnall, AJ, Firbank, MJ, Chinnery, PF, Robbins, TW, O’Brien, JT, Brooks, DJ, Burn, DJ, ICICLE-PD study group and Barker, RA (2014) Genetic impact on cognition and brain function in newly diagnosed Parkinson’s disease: ICICLE-PD study. Brain 137, 2743–2758.CrossRefGoogle ScholarPubMed
Ohadi, M, Shirazi, E, Tehranidoosti, M, Moghimi, N, Keikhaee, MR, Ehssani, S, Aghajani, A, Najmabadi, H (2006) Attention-deficit/hyperactivity disorder (ADHD) association with the DAT1 core promoter -67 T allele. Brain Research 1101, 1–4.CrossRefGoogle ScholarPubMed
Park, A and Stacy, M (2009) Non-motor symptoms in Parkinson’s disease. Journal of Neurology 256, 293–298.CrossRefGoogle ScholarPubMed
Pedersen, KF, Larsen, JP, Tysnes, OB and Alves, G (2013) Prognosis of mild cognitive impairment in early Parkinson disease: the Norwegian ParkWest study. JAMA Neurology 70, 580–586.CrossRefGoogle ScholarPubMed
Schapansky, J, Khasnavis, S, Deandrade, MP, Nardozzi, JD, Falkson, SR, Boyd, JD, Sanderson, JB, Bartels, T, Melrose, HL and LaVoie, MJ (2018) Familial knockin mutation of LRRK2 causes lysosomal dysfunction and accumulation of endogenous insoluble alpha-synuclein in neurons. Neurobiology of Disease 111, 26–35.CrossRefGoogle ScholarPubMed
Shanker, V, Groves, M, Heiman, G, Palmese, C, Saunders-Pullman, R, Ozelius, L, Raymond, D and Bressman, S (2011) Mood and cognition in leucine-rich repeat kinase 2 G2019S Parkinson’s disease. Movement Disorders 26, 1875–1880.CrossRefGoogle ScholarPubMed
Sidransky, E and Lopez, G (2012) The link between the GBA gene and parkinsonism. The Lancet Neurology 11, 986–998.CrossRefGoogle ScholarPubMed
Sohani, ZN, Meyre, D, De Souza, RJ, Joseph, PG, Gandhi, M, Dennis, BB, Norman, G and Anand, SS (2015) Assessing the quality of published genetic association studies in meta-analyses: the quality of genetic studies (Q-Genie) tool. BMC Genomics 16, 50.CrossRefGoogle ScholarPubMed
Sohani, ZN, Sarma, S, Alyass, A, De Souza, RJ, Robiou-Du-Pont, S, Li, A, Mayhew, A, Yazdi, F, Reddon, H, Lamri, A, Stryjecki, C, Ishola, A, Lee, YK, Vashi, N, Anand, SS and Meyre, D (2016) Empirical evaluation of the Q-Genie tool: a protocol for assessment of effectiveness. BMJ Open 6, e010403.CrossRefGoogle ScholarPubMed
Somme, JH, Molano Salazar, A, Gonzalez, A, Tijero, B, Berganzo, K, Lezcano, E, Fernandez Martinez, M, Zarranz, JJ and Gómez-Esteban, JC (2015) Cognitive and behavioral symptoms in Parkinson’s disease patients with the G2019S and R1441G mutations of the LRRK2 gene. Parkinsonism & Related Disorders 21, 494–499.CrossRefGoogle ScholarPubMed
Srivatsal, S, Cholerton, B, Leverenz, JB, Wszolek, ZK, Uitti, RJ, Dickson, DW, Weintraub, D, Trojanowski, JQ, Van Deerlin, VM, Quinn, JF, Chung, KA, Peterson, AL, Factor, SA, Wood-Siverio, C, Goldman, JG, Stebbins, GT, Bernard, B, Ritz, B, Rausch, R, Espay, AJ, Revilla, FJ, Devoto, J, Rosenthal, LS, Dawson, TM, Albert, MS, Mata, IF, Hu, SC, Montine, KS, Johnson, C, Montine, TJ, Edwards, KL, Zhang, J and Zabetian, CP (2015) Cognitive profile of LRRK2-related Parkinson’s disease. Movement Disorders 30, 728–733.CrossRefGoogle ScholarPubMed
Swan, M, Ortega, R, Barrett, M, Soto-Valencia, J, Boschung, S, Deik Acosta Madiedo, A, Sarva, H, Cabassa, J, Johannes, B, Raymond, D, Miravite, J, Severt, W, Sachdev, R, Shanker, V, Bressman, S and Saunders-Pullman, R (2014). Neuropsychiatric features of GBA-associated Parkinson disease. Neurology 82, P2.024.Google Scholar
Troster, AI, Fields, JA, Paolo, AM and Koller, WC (2006) Absence of the apolipoprotein E epsilon4 allele is associated with working memory impairment in Parkinson’s disease. Journal of the Neurological Sciences 248, 62–67.CrossRefGoogle ScholarPubMed
Vossius, C, Larsen, JP, Janvin, C and Aarsland, D (2011) The economic impact of cognitive impairment in Parkinson’s disease. Movement Disorders 26, 1541–1544.CrossRefGoogle ScholarPubMed
Wang, C, Cai, Y, Gu, Z, Ma, J, Zheng, Z, Tang, BS, Xu, Y, Zhou, Y, Feng, T, Wang, T, Chen, SD, Chan, P and Chinese Parkinson Study Group (2014) Clinical profiles of Parkinson’s disease associated with common leucine-rich repeat kinase 2 and glucocerebrosidase genetic variants in Chinese individuals. Neurobiology of Aging 35, 725 e1–725 e6.CrossRefGoogle ScholarPubMed
Wendland, JR, Martin, BJ, Kruse, MR, Lesch, KP and Murphy, DL (2006) Simultaneous genotyping of four functional loci of human SLC6A4, with a reappraisal of 5-HTTLPR and rs25531. Molecular Psychiatry 11, 224–226.CrossRefGoogle ScholarPubMed
West, AB, Moore, DJ, Biskup, S, Bugayenko, A, Smith, WW, Ross, CA, Dawson, VL and Dawson, TM (2005) Parkinson’s disease-associated mutations in leucine-rich repeat kinase 2 augment kinase activity. Proceedings of the National Academy of Sciences of the United States of America 102, 16842–16847.CrossRefGoogle ScholarPubMed
Williams-Gray, CH, Evans, JR, Goris, A, Foltynie, T, Ban, M, Robbins, TW, Brayne, C, Kolachana, BS, Weinberger, DR, Sawcer, SJ and Barker, RA (2009) The distinct cognitive syndromes of Parkinson’s disease: 5 year follow-up of the CamPaIGN cohort. Brain 132, 2958–2969.CrossRefGoogle ScholarPubMed
Williams-Gray, CH, Goris, A, Saiki, M, Foltynie, T, Compston, DA, Sawcer, SJ and Barker, RA (2009) Apolipoprotein E genotype as a risk factor for susceptibility to and dementia in Parkinson’s disease. Journal of Neurology 256, 493–498.CrossRefGoogle ScholarPubMed
Williams-Gray, CH, Hampshire, A, Barker, RA and Owen, AM (2008) Attentional control in Parkinson’s disease is dependent on COMT val 158 met genotype. Brain 131, 397–408.CrossRefGoogle ScholarPubMed
Zheng, J, Yang, X, Zhao, Q, Tian, S, Huang, H, Chen, Y and Xu, Y (2017) Association between gene polymorphism and depression in Parkinson’s disease: A case-control study. Journal of the Neurological Sciences 375, 231–234.CrossRefGoogle ScholarPubMed
Zheng, Y, Pei, Z, Liu, Y, Zhou, H, Xian, W, Fang, Y, Chen, L and Wu, Q (2015) Cognitive impairments in LRRK2-related Parkinson’s disease: a study in Chinese individuals. Behavioural Neurology 2015, 5.CrossRefGoogle ScholarPubMed
Zokaei, N, Mcneill, A, Proukakis, C, Beavan, M, Jarman, P, Korlipara, P, Hughes, D, Mehta, A, Hu, MT, Schapira, AH and Husain, M (2014) Visual short-term memory deficits associated with GBA mutation and Parkinson’s disease. Brain 137, 2303–2311.CrossRefGoogle ScholarPubMed
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