Biology subjects

Camicioli, R.

Publications and source records attributed to Camicioli, R..

4 recordsLinked to original sources

bioRxiv2020

Amyloid β Impacts Future Freezing of Gait in Parkinson's Disease Via White Matter Hyperintensities

BackgroundFreezing of gait (FOG) is a common symptom in Parkinsons Disease (PD) patients. Previous studies have reported relationships between FOG, substantia nigra (SN) degeneration, dopamine transporter (DAT) concentration, as well as amyloid {beta} deposition. However, there is a paucity of research on the concurrent impact of white matter damage. ObjectivesTo assess the inter-relationships between these different co-morbidities, their impact on future FOG and whether they act independently of each other. MethodsWe used baseline MRI and longitudinal gait data from the Parkinsons Progression Markers Initiative (PPMI). We used deformation based morphometry (DBM) from T1-weighted MRI to measure SN atrophy, and segmentation of white matter hyperintensities (WMH) as a measure of WM pathological load. Putamen and caudate DAT levels from SPECT as well as cerebrospinal fluid (CSF) amyloid {beta} were obtained directly from the PPMI. Following correlation analyses, we investigated whether WMH burden mediates the impact of amyloid {beta} on future FOG. ResultsSN DBM, WMH load, putamen and caudate DAT activity and CSF amyloid {beta} levels were significantly different between PD patients with and without future FOG (p < 0.008). Mediation analysis demonstrated an effect of CSF amyloid {beta} levels on future FOG via WMH load, independent of SN atrophy and striatal DAT activity levels. ConclusionsAmyloid {beta} might impact future FOG in PD patients through an increase in WMH burden, in a pathway independent of Lewy body pathology.

neuroscience↗

bioRxiv2020

Beware of White Matter Hyperintensities Causing Systematic Errors in Grey Matter Segmentations!

IntroductionVolumetric estimates of subcortical and cortical structures, extracted from T1-weighted MRIs, are widely used in many clinical and research applications. Here, we investigate the impact of the presence of white matter hyperintensities (WMHs) on FreeSurfer grey matter (GM) structure volumes and its possible bias on functional relationships. MethodsT1-weighted images from 1077 participants (4321 timepoints) from the Alzheimers Disease Neuroimaging Initiative were processed with FreeSurfer version 6.0.0. WMHs were segmented using a previously validated algorithm on either T2-weighted or Fluid-attenuated inversion recovery (FLAIR) images. Mixed effects models were used to assess the relationships between overlapping WMHs and GM structure volumes and overal WMH burden, as well as to investigate whether such overlaps impact associations with age, diagnosis, and cognitive performance. ResultsParticipants with higher WMH volumes had higher overalps with GM volumes of bilateral caudate, cerebral cortex, putamen, thalamus, pallidum, and accumbens areas (P < 0.0001). When not corrected for WMHs, caudate volumes increased with age (P < 0.0001) and were not different between cognitively healthy individuals and age-matched probable Alzheimers disease patients. After correcting for WMHs, caudate volumes decreased with age (P < 0.0001), and Alzheimers disease patients had lower caudate volumes than cognitively healthy individuals (P < 0.01). Uncorrected caudate volume was not associated with ADAS13 scores, whereas corrected lower caudate volumes were significantly associated with poorer cognitive performance (P < 0.0001). ConclusionsPresence of WMHs leads to systematic inaccuracies in GM segmentations, particularly for the caudate, which can also change clinical associations. While specifically measured for the Freesurfer toolkit, this problem likely affects other algorithms.

neuroscience↗

bioRxiv2020

The Temporal Relationships between White Matter Hyperintensities, Neurodegeneration, Amyloid β, and Cognition

INTRODUCTIONCognitive decline in Alzheimers disease is associated with amyloid-{beta} accumulation, neurodegeneration and cerebral small vessel disease, but the temporal relationships between these factors is not well established. METHODSData included white matter hyperintensity (WMH) load, grey matter (GM) atrophy and Alzheimers Disease Assessment Scale-Cognitive-Plus (ADAS13) scores for 720 participants and cerebrospinal fluid amyloid (A{beta}1-42) for 461 participants from the Alzheimers Disease Neuroimaging Initiative. Linear regressions were used to assess the relationships between baseline WMH, GM, and A{beta}1-42 to changes in WMH, GM, A{beta}1-42, and cognition at one-year follow-up. RESULTSBaseline WMHs and A{beta}1-42 predicted WMH increase and GM atrophy. Baseline WMHs, GM, and A{beta}1-42 predicted worsening cognition. Only baseline A{beta}1-42 predicted change in A{beta}1-42. DISCUSSIONBaseline WMHs lead to greater future GM atrophy and cognitive decline, suggesting that WM damage precedes neurodegeneration and cognitive decline. Baseline A{beta}1-42 predicted WMH increase, suggesting a potential role of amyloid in WM damage. Research in ContextO_LISystematic Review: Both amyloid {beta} and neurodegeneration are primary pathologies in Alzheimers disease. White matter hyperintensities (indicative of presence of cerebrovascular disease) might also be part of the pathological changes in Alzheimers. However, the temporal relationship between white matter hyperintensities, amyloid {beta}, neurodegeneration, and cognitive decline is still unclear. C_LIO_LIInterpretation: Our results establish a potential temporal order between white matter hyperintensities, amyloid {beta}, neurodegeneration, and cognitive decline, showing that white matter hyperintensities precede neurodegeneration and cognitive decline. The results provide some evidence that amyloid {beta} deposition, in turn, precedes accumulation of white matter hyperintensities. C_LIO_LIFuture Directions: The current findings reinforce the need for future longitudinal investigations of the mechanisms through which white matter hyperintensities impact the aging population in general and Alzheimers disease patients, in particular. C_LI

neuroscience↗

bioRxiv2020

Cognitive and Motor Correlates of Grey and White Matter Pathology in Parkinsons Disease

IntroductionPrevious studies have found associations between grey matter atrophy and white matter hyperintensities (WMH) of vascular origin with cognitive and motor deficits in Parkinsons disease (PD). Here we investigate these relationships in a sample of PD patients and age-matched healthy controls. MethodsData included 50 PD patients and 45 age-matched controls with T1-weighted and FLAIR scans at baseline, 18-months, and 36-months follow-up. Deformation-based morphometry was used to measure grey matter atrophy. SNIPE (Scoring by Nonlocal Image Patch Estimator) was used to measure Alzheimers disease-like textural patterns in the hippocampi. WMHs were segmented using T1-weighted and FLAIR images. The relationship between MRI features and clinical scores was assessed using mixed-effects models. The motor subscore of the Unified Parkinsons Disease Rating Scale (UPDRSIII), number of steps in a walking trial, and Dementia Rating Scale (DRS) were used respectively as measures of motor function, gait, and cognition. ResultsSubstantia nigra atrophy was significantly associated with motor deficits, with a greater impact in PDs (p<0.05). Hippocampal SNIPE scores were associated with cognitve decline in both PD and controls (p<0.01). WMH burden was significantly associated with cognitive decline and increased motor deficits in the PD group, and gait deficits in both PD and controls (p<0.03). ConclusionWhile substantia nigra atrophy and WMH burden were significantly associated with additional motor deficits, WMH burden and hippocampal atrophy were associated with cognitive deficits in PD patients. These results suggest an additive contribution of both grey and white matter damage to the motor and cognitive deficits in PD.

neuroscience↗