Dataset Information

Coevolution of white matter hyperintensities and cognition in the elderly.

ABSTRACT:

Objective

To investigate the effects of baseline white matter hyperintensity (WMH) and rates of WMH extension and emergence on rate of change in cognition (episodic memory and executive function).

Methods

A total of 150 individuals including cognitively normal elderly individuals and those with Alzheimer disease and mild cognitive impairment completed serial episodic memory and executive function evaluations and serial MRI scans sufficient for longitudinal measurement of WMH (mean delay 4.0 years). Incident WMH voxels were categorized as extended (baseline WMH that grew larger) or emergent (newly formed WMH). We used a stepwise regression approach to investigate the effects of baseline WMH and rates of WMH extension and emergence on rate of change in cognition (episodic memory and executive function).

Results

WMH burden significantly increased over time, and approximately 80% of incident WMH voxels represented extensions of existing lesions. Each 1 mL/y increase in WMH extension was associated with an additional 0.70 SD/y of subsequent episodic memory decrease (p = 0.0053) and an additional 0.55 SD/y of subsequent executive function decrease (p = 0.022). Emergent WMHs were not found to be associated with a change in cognitive measures.

Conclusions

Aging-associated WMHs evolve significantly over a 4-year period. Most of this evolution represents worsening injury to the already compromised surround of existing lesions. Increasing WMH was also significantly associated with declining episodic memory and executive function. This finding supports the view that white matter disease is an insidious and continuously evolving process whose progression has clinically relevant cognitive consequences.

SUBMITTER: Maillard P

PROVIDER: S-EPMC3405254 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature

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Publications

Coevolution of white matter hyperintensities and cognition in the elderly.

Maillard Pauline P Carmichael Owen O Fletcher Evan E Reed Bruce B Mungas Dan D DeCarli Charles C

Neurology 20120718 5

<h4>Objective</h4>To investigate the effects of baseline white matter hyperintensity (WMH) and rates of WMH extension and emergence on rate of change in cognition (episodic memory and executive function).<h4>Methods</h4>A total of 150 individuals including cognitively normal elderly individuals and those with Alzheimer disease and mild cognitive impairment completed serial episodic memory and executive function evaluations and serial MRI scans sufficient for longitudinal measurement of WMH (mean ...[more]

PMID: 22815562

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Project description:Background:Patients with Parkinson's disease (PD) present with a broad spectrum of nonmotor features including autonomic disorders. More severe autonomic dysfunction in PD is associated with increased cognitive deficits. The presence of cerebral small-vessel disease, measured by T2-weighted magnetic resonance imaging white matter hyperintensity (WMH) burden, is also observed in patients with PD with faster cognitive decline. Objective:To investigate whether baseline orthostatic hypotension and autonomic dysfunction in early-stage PD affect later cognitive decline via mediation through cerebral small-vessel disease. Methods:De novo PD patients (N = 365) and age-matched controls (N = 174) with baseline T2-weighted/ fluid-attenuated inversion recovery scans were selected from the Parkinson's Progression Markers Initiative. WMHs were automatically segmented. Mediation analysis was used to assess whether WMH load mediates the effect of orthostatic hypotension and autonomic dysfunction (measured by Scales for Outcomes in Parkinson's Disease-Autonomic) on future cognitive decline (measured by Montreal Cognitive Assessment) in an average of 4 years of follow-up. Results:Mediation analysis supported the existence of a full mediation of WMHs on the effect of diastolic orthostatic hypotension in patients with PD and future cognitive decline (average causal mediation effect: ab = -0.032, 95% confidence interval = -0.064 to -0.01, P = 0.01). There was also a partial mediation for overall autonomic dysfunction (ab = -0.027, 95% confidence interval = -0.054 to 0.00, P = 0.02). Conclusions:WMHs fully mediate the effect of diastolic orthostatic hypotension and partially mediate the effect of autonomic dysregulation on future cognitive decline in patients with PD. Our findings support the hypothesis that autonomic dysfunction in early clinical stages predisposes the brain to WMHs through dysregulation of the blood flow in the small vessels. This in turn increases the risk of future cognitive impairment in early PD.

Project description:ObjectivesTo study the interactive effect of white matter hyperintensities (WMH) and hippocampal atrophy on cognition in the oldest old.DesignOngoing longitudinal study.SettingIn Southern California, brain magnetic resonance imaging (MRI) scans were conducted between May 2014 and December 2017.ParticipantsIndividuals from The 90+ Study with a valid brain MRI scan (N = 141; 94 cognitively normal and 47 with cognitive impairment).MeasurementsCognitive testing was performed every 6 months with a mean follow-up of 2 years and included these tests: Mini-Mental State Examination (MMSE), modified MMSE (3MS), California Verbal Learning Test (CVLT) immediate recall over four trials and delayed recall, Digit Span Backward, Animal Fluency, and Trail Making Test (TMT) A, B, and C. We used one linear mixed model for each cognitive test to study the baseline and longitudinal association of WMH and hippocampal volume (HV) with cognition. Models were adjusted for age, sex, and education.ResultsMean age was 94.3 years (standard deviation [SD] = 3.2 y). At baseline, higher WMH volumes were associated with worse scores on the 3MS, CVLT immediate and delayed recall, and TMT B. Lower HVs were associated with worse baseline scores on all cognitive tests, except for the Digit Span Backward. Longitudinally, higher WMH and lower HVs were associated with faster decline in the 3MS and MMSE, and lower HV was also associated with faster decline in the CVLT immediate recall. No association was observed between WMH and HV and no interaction between WMH and HV in their association with baseline cognition or cognitive decline.ConclusionWe show that WMH and hippocampal atrophy have an independent, negative effect on cognition that make these biomarkers relevant to evaluate in the diagnostic work-up of the oldest-old individuals with cognitive complaints. However, the predictive value of WMH for cognitive decline seems to be less evident in the oldest-old compared with a younger group of older adults. J Am Geriatr Soc 67:1827-1834, 2019.

Project description:BackgroundManual segmentation is currently the gold standard to assess white matter hyperintensities (WMH), but it is time consuming and subject to intra and inter-operator variability.PurposeTo compare automatic methods to segment white matter hyperintensities (WMH) in the elderly in order to assist radiologist and researchers in selecting the most relevant method for application on clinical or research data.Material and methodsWe studied a research dataset composed of 147 patients, including 97 patients from the Alzheimer's Disease Neuroimaging Initiative (ADNI) 2 database and 50 patients from ADNI 3 and a clinical routine dataset comprising 60 patients referred for cognitive impairment at the Pitié-Salpêtrière hospital (imaged using four different MRI machines). We used manual segmentation as the gold standard reference. Both manual and automatic segmentations were performed using FLAIR MRI. We compared seven freely available methods that produce segmentation mask and are usable by a radiologist without a strong knowledge of computer programming: LGA (Schmidt et al., 2012), LPA (Schmidt, 2017), BIANCA (Griffanti et al., 2016), UBO detector (Jiang et al., 2018), W2MHS (Ithapu et al., 2014), nicMSlesion (with and without retraining) (Valverde et al., 2019, 2017). The primary outcome for assessing segmentation accuracy was the Dice similarity coefficient (DSC) between the manual and the automatic segmentation software. Secondary outcomes included five other metrics.ResultsA deep learning approach, NicMSlesion, retrained on data from the research dataset ADNI, performed best on this research dataset (DSC: 0.595) and its DSC was significantly higher than that of all others. However, it ranked fifth on the clinical routine dataset and its performance severely dropped on data with artifacts. On the clinical routine dataset, the three top-ranked methods were LPA, SLS and BIANCA. Their performance did not differ significantly but was significantly higher than that of other methods.ConclusionThis work provides an objective comparison of methods for WMH segmentation. Results can be used by radiologists to select a tool.

Dataset Information

Coevolution of white matter hyperintensities and cognition in the elderly.

Objective

Methods

Results

Conclusions

Publications

Coevolution of white matter hyperintensities and cognition in the elderly.

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