@article{Nombela:2014:brain/awu201,
author = {Nombela, C and Rowe, JB and Winder-Rhodes, SE and Hampshire, A and Owen, AM and Breen, DP and Duncan, GW and Khoo, TK and Yarnall, AJ and Firbank, MJ and Chinnery, PF and Robbins, TW and O'Brien, JT and Brooks, DJ and Burn, DJ and Barker, RA},
doi = {brain/awu201},
journal = {Brain},
pages = {2743--2758},
title = {Genetic impact on cognition and brain function in newly diagnosed Parkinson's disease: ICICLE-PD study},
url = {http://dx.doi.org/10.1093/brain/awu201},
volume = {137},
year = {2014}
}

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TY  - JOUR
AB  - Parkinson’s disease is associated with multiple cognitive impairments and increased risk of dementia, but the extent of these deficits varies widely among patients. The ICICLE-PD study was established to define the characteristics and prevalence of cognitive change soon after diagnosis, in a representative cohort of patients, using a multimodal approach. Specifically, we tested the ‘Dual Syndrome’ hypothesis for cognitive impairment in Parkinson’s disease, which distinguishes an executive syndrome (affecting the frontostriatal regions due to dopaminergic deficits) from a posterior cortical syndrome (affecting visuospatial, mnemonic and semantic functions related to Lewy body pathology and secondary cholinergic loss). An incident Parkinson’s disease cohort (n = 168, median 8 months from diagnosis to participation) and matched control group (n = 85) were recruited to a neuroimaging study at two sites in the UK. All participants underwent clinical, neuropsychological and functional magnetic resonance imaging assessments. The three neuroimaging tasks (Tower of London, Spatial Rotations and Memory Encoding Tasks) were designed to probe executive, visuospatial and memory encoding domains, respectively. Patients were also genotyped for three polymorphisms associated with cognitive change in Parkinson’s disease and related disorders: (i) rs4680 for COMT Val158Met polymorphism; (ii) rs9468 for MAPT H1 versus H2 haplotype; and (iii) rs429358 for APOE-ε2, 3, 4. We identified performance deficits in all three cognitive domains, which were associated with regionally specific changes in cortical activation. Task-specific regional activations in Parkinson’s disease were linked with genetic variation: the rs4680 polymorphism modulated the effect of levodopa therapy on planning-related activations in the frontoparietal network; the MAPT haplotype modulated parietal activations associated with spatial rotations; and APOE allelic varia
AU  - Nombela,C
AU  - Rowe,JB
AU  - Winder-Rhodes,SE
AU  - Hampshire,A
AU  - Owen,AM
AU  - Breen,DP
AU  - Duncan,GW
AU  - Khoo,TK
AU  - Yarnall,AJ
AU  - Firbank,MJ
AU  - Chinnery,PF
AU  - Robbins,TW
AU  - O'Brien,JT
AU  - Brooks,DJ
AU  - Burn,DJ
AU  - Barker,RA
DO  - brain/awu201
EP  - 2758
PY  - 2014///
SN  - 0006-8950
SP  - 2743
TI  - Genetic impact on cognition and brain function in newly diagnosed Parkinson's disease: ICICLE-PD study
T2  - Brain
UR  - http://dx.doi.org/10.1093/brain/awu201
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000343420900020&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://academic.oup.com/brain/article/137/10/2743/2847330
VL  - 137
ER  - 

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