Structural and functional imaging study in dementia with Lewy bodies and Parkinson's disease dementia

Borroni, Barbara; Premi, Enrico; Formenti, Anna Maria; Turrone, Rosanna; Alberici, Antonella; Cottini, Elisabetta; Rizzetti, Cristina; Gasparotti, Roberto; Padovani, Alessandro

doi:10.1016/j.parkreldis.2015.06.013

Cited by 73 publications

(54 citation statements)

References 28 publications

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“…Cognitive function is associated with cortical atrophy in PD patients, such that PD patients with cognitive impairments may show more extensive cortical atrophy and decreased cortical perfusion compared with PD patients without cognitive impairments (Ibarretxe-Bilbao et al, 2009; Chen et al, 2016; Lin et al, 2016) Relatedly, in PD patients with dementia, a previous study reported extensive frontal and subcortical atrophy compared with PD patients with no cognitive impairment (Borroni et al, 2015). The results of this study, meanwhile, show extensive WM changes even in the early stages of the disease.…”

Section: Discussionmentioning

confidence: 99%

Associations among Cognitive Functions, Plasma DNA, and White Matter Integrity in Patients with Early-Onset Parkinson's Disease

Chen

et al. 2017

Front. Neurosci.

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Early-onset Parkinson's disease (EOPD) patients are symptomatic at a relatively young age, and the impacts of the disease on both the patients and their caregivers are dramatic. Few studies have reported on the cognitive impairments seen in EOPD, and the results of these studies have been diverse. Furthermore, it is still unclear what microstructural white matter (WM) changes are present in EOPD patients. As such, we conducted this study to investigate the microstructural WM changes experienced by EOPD patients and their association with cognitive function and plasma DNA levels. We enrolled 24 EOPD patients and 33 sex- and age-matched healthy volunteers who underwent complete neuro-psychological testing (NPT) to evaluate their cognitive function and diffusion tensor imaging (DTI) scanning to determine their fiber integrity. The plasma DNA measurements included measurements of nuclear and mitochondrial DNA levels. Fractional anisotropy (FA) maps were compared using voxel-based statistics to determine differences between the two groups. The differences in DTI indices and NPT scores were correlated after adjusting for age, sex, and education. Our results demonstrate that patients with EOPD have elevated nuclear DNA levels and wide spectrums of impairments in NPT, especially in the executive function and visuospatial function domains. Exploratory group-wise comparisons of the DTI indices revealed that the patients with EOPD exhibited lower DTI parameters in several brain locations. These poorer DTI parameters were associated with worse cognitive performances and elevated plasma nuclear DNA levels, especially in the anterior thalamic radiation region. Our findings suggest that the thalamus and its adjacent anterior thalamic radiation may be important in the pathogenesis of EOPD, as they appear to become involved in the disease process at an early stage.

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Section: Discussionmentioning

confidence: 99%

Associations among Cognitive Functions, Plasma DNA, and White Matter Integrity in Patients with Early-Onset Parkinson's Disease

Chen

et al. 2017

Front. Neurosci.

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“…At the time when a PDD diagnosis is established, cortical thinning becomes more severe in parietal, occipital, temporal and frontal cortices, and the volume loss in the hippocampus is substantial, including atrophy of the parahippocampus, insula and cingulate gyrus, which is associated with further decline of cognitive functions 122–125 . The pattern of cortical thinning has also been suggested to differentiate PDD, which is characterized by predominant frontal cortex thinning, from DLB, which is characterized by predominant thinning of the parietal and occipital cortices 126 .…”

Section: Biomarkers Of Cognitive Decline In Pdmentioning

confidence: 99%

Cognitive decline in Parkinson disease

et al. 2017

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Dementia is a frequent problem encountered in advanced stages of Parkinson disease (PD). In recent years, research has focused on the pre-dementia stages of cognitive impairment in PD, including mild cognitive impairment (MCI). Several longitudinal studies have shown that MCI is a harbinger of dementia in PD, although the course is variable, and stabilization of cognition — or even reversal to normal cognition — is not uncommon. In addition to limbic and cortical spread of Lewy pathology, several other mechanisms are likely to contribute to cognitive decline in PD, and a variety of biomarker studies, some using novel structural and functional imaging techniques, have documented in vivo brain changes associated with cognitive impairment. The evidence consistently suggests that low cerebrospinal fluid levels of amyloid-β42, a marker of comorbid Alzheimer disease (AD), predict future cognitive decline and dementia in PD. Emerging genetic evidence indicates that in addition to the APOE*ε4 allele (an established risk factor for AD), GBA mutations and SCNA mutations and triplications are associated with cognitive decline in PD, whereas the findings are mixed for MAPT polymorphisms. Cognitive enhancing medications have some effect in PD dementia, but no convincing evidence that progression from MCI to dementia can be delayed or prevented is available, although cognitive training has shown promising results.

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“…In PD, ALFF and ReHo are abnormal throughout the brain including the striatum (Wu et al, 2009; Hou et al, 2014; Sheng et al, 2016; Xiang et al, 2016), frontal or sensorimotor areas (Wu et al, 2009; Skidmore et al, 2013; Yang et al, 2013; Borroni et al, 2015; Hu X. F. et al, 2015; Li et al, 2016; Xiang et al, 2016), temporal, parietal, and/or occipital cortex (Wu et al, 2009; Long et al, 2012; Choe et al, 2013; Yang et al, 2013; Zhang et al, 2013; Hu X. F. et al, 2015; Luo et al, 2015; Li et al, 2016; Sheng et al, 2016), and the cerebellum (Wu et al, 2009; Skidmore et al, 2013; Sheng et al, 2014; Chen et al, 2015). While these findings suggest extensive disturbances in both metrics, considerable discrepancies exist across studies in regional abnormalities and whether ALFF and ReHo are increased or decreased in PD relative to controls.…”

Section: Introductionmentioning

confidence: 99%

“…While these findings suggest extensive disturbances in both metrics, considerable discrepancies exist across studies in regional abnormalities and whether ALFF and ReHo are increased or decreased in PD relative to controls. Conflicting results may be due to small PD samples (11 to ≈20) (Wu et al, 2009; Long et al, 2012; Skidmore et al, 2013; Yang et al, 2013; Borroni et al, 2015; Hu X. F. et al, 2015; Li et al, 2016) and testing patients on dopamine medication (Zhang et al, 2013; Hu X. et al, 2015; Hu X. F. et al, 2015; Lucas-Jimenez et al, 2016; Xiang et al, 2016), which alters ALFF and ReHo (Wu et al, 2009; Hou et al, 2014). Most notably, few studies have applied the Movement Disorders Society Task Force Level II criteria to screen for MCI in PD cohorts (Litvan et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Aberrant Intrinsic Activity and Connectivity in Cognitively Normal Parkinson’s Disease

Harrington

Shen

Castillo

et al. 2017

Front. Aging Neurosci.

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Disturbances in intrinsic activity during resting-state functional MRI (rsfMRI) are common in Parkinson’s disease (PD), but have largely been studied in a priori defined subnetworks. The cognitive significance of abnormal intrinsic activity is also poorly understood, as are abnormalities that precede the onset of mild cognitive impairment. To address these limitations, we leveraged three different analytic approaches to identify disturbances in rsfMRI metrics in 31 cognitively normal PD patients (PD-CN) and 30 healthy adults. Subjects were screened for mild cognitive impairment using the Movement Disorders Society Task Force Level II criteria. Whole-brain data-driven analytic approaches first analyzed the amplitude of low-frequency intrinsic fluctuations (ALFF) and regional homogeneity (ReHo), a measure of local connectivity amongst functionally similar regions. We then examined if regional disturbances in these metrics altered functional connectivity with other brain regions. We also investigated if abnormal rsfMRI metrics in PD-CN were related to brain atrophy and executive, visual organization, and episodic memory functioning. The results revealed abnormally increased and decreased ALFF and ReHo in PD-CN patients within the default mode network (posterior cingulate, inferior parietal cortex, parahippocampus, entorhinal cortex), sensorimotor cortex (primary motor, pre/post-central gyrus), basal ganglia (putamen, caudate), and posterior cerebellar lobule VII, which mediates cognition. For default mode network regions, we also observed a compound profile of altered ALFF and ReHo. Most regional disturbances in ALFF and ReHo were associated with strengthened long-range interactions in PD-CN, notably with regions in different networks. Stronger long-range functional connectivity in PD-CN was also partly expanded to connections that were outside the networks of the control group. Abnormally increased activity and functional connectivity appeared to have a pathological, rather than compensatory influence on cognitive abilities tested in this study. Receiver operating curve analyses demonstrated excellent sensitivity (≥90%) of rsfMRI variables in distinguishing patients from controls, but poor accuracy for brain volume and cognitive variables. Altogether these results provide new insights into the topology, cognitive relevance, and sensitivity of aberrant intrinsic activity and connectivity that precedes clinically significant cognitive impairment. Longitudinal studies are needed to determine if these neurocognitive associations presage the development of future mild cognitive impairment or dementia.

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Structural and functional imaging study in dementia with Lewy bodies and Parkinson's disease dementia

Cited by 73 publications

References 28 publications

Associations among Cognitive Functions, Plasma DNA, and White Matter Integrity in Patients with Early-Onset Parkinson's Disease

Associations among Cognitive Functions, Plasma DNA, and White Matter Integrity in Patients with Early-Onset Parkinson's Disease

Cognitive decline in Parkinson disease

Aberrant Intrinsic Activity and Connectivity in Cognitively Normal Parkinson’s Disease

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