Neurodegeneration Across Stages of Cognitive Decline in Parkinson Disease

Weintraub, Daniel; Doshi, Jimit; Koka, Deepthi; Davatzikos, Christos; Siderowf, Andrew; Duda, John E.; Wolk, David A.; Moberg, Paul J.; Xie, Sharon X.; Clark, Christopher M.

doi:10.1001/archneurol.2011.725

Cited by 182 publications

(161 citation statements)

References 49 publications

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“…We found that MCI in PD was associated with temporal, parietal, and frontal cortical thinning. Contrary to previous assumptions that atrophy does not accompany PD per se or in the absence of cognitive impairment, 22,23 temporal thinning was also observed in patients with PD who did not meet criteria for MCI. Memory, visuospatial, and executive cognitive tests were mainly related to temporoparietal and superior frontal thinning, suggesting a relationship between cognitive impairment and both anterior and posterior cortical atrophy in PD.…”

Section: Vertex-wise Comparisons Of Cortical Thickness Between (A) Cocontrasting

confidence: 99%

Initial cognitive decline is associated with cortical thinning in early Parkinson disease

et al. 2014

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Objectives: Our aim was to assess cortical thickness in a large multicenter cohort of drug-naive patients with early Parkinson disease (PD), with and without mild cognitive impairment (MCI), and explore the cognitive correlates of regional cortical thinning.Methods: One hundred twenty-three newly diagnosed patients with PD and 56 healthy controls with 3-tesla structural MRI scans and complete neuropsychological assessment from the Parkinson's Progression Markers Initiative were included. Modified Movement Disorders Society Task Force level II criteria were applied to diagnose MCI in PD. FreeSurfer image processing and analysis software was used to measure cortical thickness across groups and the association with cognitive domains and tests.Results: In patients with MCI, atrophy was found in temporal, parietal, frontal, and occipital areas compared with controls. Specific regional thinning in the right inferior temporal cortex was also found in cognitively normal patients. Memory, executive, and visuospatial performance was associated with temporoparietal and superior frontal thinning, suggesting a relationship between cognitive impairment and both anterior and posterior cortical atrophy in the whole patient sample.Conclusions: These findings confirm that MCI is associated with widespread cortical atrophy. In addition, they suggest that regional cortical thinning is already present at the time of diagnosis in patients with early, untreated PD who do not meet the criteria for MCI. Together, the results indicate that cortical thinning can serve as a marker for initial cognitive decline in early PD.

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Section: Vertex-wise Comparisons Of Cortical Thickness Between (A) Cocontrasting

confidence: 99%

Initial cognitive decline is associated with cortical thinning in early Parkinson disease

et al. 2014

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“…Magnetic resonance imaging of the brains of 84 PD patients (61 PD with normal cognition; 12 PD-MCI; 11 PD dementia) and 23 healthy control subjects found no abnormalities PD subjects with normal cognition, hippocampal atrophy in subjects with PD-MCI, and both hippocampal and medial temporal atrophy in those with PD dementia. 29 These results confirm that hippocampal atrophy is a biomarker of initial cognitive decline in PD. Marked grey matter atrophy has also been observed in patients with PD dementia with less extensive changes in those with PD-MCI.…”

Section: Investigation Of Neurotransmitters Involved In Cognitive Decsupporting

confidence: 65%

Extending our Understanding of the Dopaminergic Basis of Non-motor Symptoms in Parkinson’s Disease

Korczyn

Chaudhuri²,

Laar

2015

European Neurological Review

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Parkinson's disease (PD) is primarily considered as a motor disorder but there is increasing recognition of the wide range of non-motor symptoms (NMS), such as low mood, pain, apathy, fatigue and sleep problems, which may be experienced by PD patients across the spectrum of the disease. Notably, NMS often occur before motor symptoms develop and are known to place a significant burden on health-related quality of life (HRQoL) of the person with PD. Commonly, NMS go undiagnosed by the clinician and are therefore undertreated; however, to optimise patient outcomes, both motor and non-motor aspects of PD need to be recognised and managed that it is the total 'burden' of NMS, combining frequency and severity, and not just the occurrence of individual NMS such as depression, which is the major determinant of a patient's HRQoL. Recognising the significant contribution of NMS to the total clinical picture in PD, in order to provide a more comprehensive grading of PD severity, it is now proposed that the clinical assessment of PD patients needs a combined approach using for example the validated Non-motor Symptoms Scale (NMSS) to assess total NMS burden in addition to classic motor symptom scoring. Recent data from newly diagnosed PD patients also suggests there are different subtypes of PD that may have implications for both clinical trial design and the selection of therapy. Cognitive impairment often occurs in patients with PD, even in early disease, progressing to PD dementia in a substantial proportion of patients, which can limit therapeutic options. Posterior cortical dysfunction is a negative predictor of the progression of PD with mild cognitive impairment to PD dementia. Pronounced nigrostriatal denervation is characteristic of PD; however, cholinergic changes are also observed. Cholinergic depletion starts early in the disease process and by the time PD dementia develops patients will have a significant cholinergic deficit in various cortical regions.Current research is focused on the potential to reduce cognitive decline by decreasing beta-amyloid plaques. KeywordsParkinson's disease (PD), non-motor symptoms, dopamine, cognitive impairment, apomorphine Disclosure: Amos D Korczyn has received honoraria for sponsored symposia in educational meetings from Britannia. K Ray Chaudhuri has received honoraria for sponsored symposia in educational meetings from AbbVie, Britannia, Mundipharma, Otsuka, UCB and US WorldMeds. He has received educational grants from AbbVie, Britannia, Medtronic and UCB. Teus van Laar has received honoraria for sponsored symposia in educational meetings from AbbVie, Britannia, UCB and Medtronic.

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“…Moreover, large-scale epidemiological studies observed cognitive impairments in up to 20% of PD patients at disease onset ); in advanced stages, more than 80% of patients may develop dementia (Hely et al 2008). Recent studies in PD patients point to an early affection of the hippocampus and olfactory bulb (OB) in the disease process (Braak et al 2003;Weintraub et al 2011;Carlesimo et al 2012), making the investigation of adult hippocampal and OB/SVZ neurogenesis the focus of research.…”

Section: Pd: Disease Mechanismsmentioning

confidence: 99%