Do white matter changes contribute to the subsequent development of dementia in patients with mild cognitive impairment? A longitudinal study

Wolf, Henrike; Ecke, Gustav Martin; Bettin, S.; Dietrich, Joachim; Gertz, Hermann‐Josef

doi:10.1002/1099-1166(200009)15:9<803::aid-gps190>3.0.co;2-w

Cited by 101 publications

(18 citation statements)

References 51 publications

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“…A few studies have shown that WMLs in people with MCI increase the risk of future dementia [8,9], but others contradict this finding [10,11]. While previous studies have investigated the role of WMLs in full-blown dementia due to AD [12,13], less is known about how these changes affect patients with milder memory complaints.…”

Section: Introductionmentioning

confidence: 99%

Tau Pathology and Parietal White Matter Lesions Have Independent but Synergistic Effects on Early Development of Alzheimer's Disease

Hertze

Palmqvist

Minthon

et al. 2013

Dement Geriatr Cogn Disord Extra

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Background: White matter lesions (WMLs) are a common finding in patients with dementia. This study investigates the relationship between WMLs, hyperphosphorylated tau (P-tau) in cerebrospinal fluid (CSF) and apolipoprotein E (APOE) ε4 genotype in prodromal Alzheimer's disease (AD). Methods: Baseline levels of tau, P-tau and β-amyloid 1-42 in CSF, the presence of WMLs in the brain, and the APOE genotype were ascertained in 159 patients with mild cognitive impairment (MCI) and 38 cognitively healthy controls. Results: After 5.7 years, 58 patients had developed AD. In this group, patients with normal levels of CSF P-tau had higher levels of WMLs in the parietal regions than those with pathological P-tau levels (p < 0.05). Also, patients without APOE ε4 alleles had more WMLs in the parietal lobes than those with at least one allele (p < 0.05). MCI patients with pathological P-tau levels and parietal WMLs showed a greater risk of developing AD than those with just one of the two pathological parameters. Conclusions: We suggest that WMLs in parietal lobes and tau pathology likely have independent but synergistic effects on the reduction of the cognitive reserve capacity of the brain. In patients with a more low-grade AD pathology, WMLs in the parietal lobes might increase the risk of developing dementia.

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Section: Introductionmentioning

confidence: 99%

Tau Pathology and Parietal White Matter Lesions Have Independent but Synergistic Effects on Early Development of Alzheimer's Disease

Hertze

Palmqvist

Minthon

et al. 2013

Dement Geriatr Cogn Disord Extra

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“…WMH burden increases in healthy aging but is also related to risk factors such as hypertension, heart disease, and diabetes (Breteler et al, 1994; DeCarli et al, 1995; Debette et al, 2010). WMHs are typically greater in older adults with mild cognitive impairment (MCI) and dementia than in healthy older adults (Wu et al, 2002; Wolf et al, 2000), and have been related to cognition in all three groups (DeCarli et al, 2005; Elias et al, 2004; Lopez et al, 2003; Gunning-Dixon & Raz, 2000; Wu et al, 2002). Longitudinal data have supported the cross-sectional findings and have indicated a relationship between WMH burden and cognitive performance, with increasing WMH burden associated with decreasing cognitive functioning, particularly with regard to executive function and processing speed (DeGroot et al, 2001; Gunning-Dixon & Raz, 200; Kramer, Reed, Mungas, Weiner, Chui, 2002; Prins, Van Dijk, den Heijer, et al, 2005; Vannorsdall, Waldstein, Kraut, Pearlson, & Schretlen, 2009).…”

Section: Introductionmentioning

confidence: 99%

Executive function mediates effects of white matter hyperintensities on episodic memory

et al. 2011

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This study examined the relationship between white matter hyperintensities (WMH) and executive functioning on episodic memory in a group of older adults who were cognitively normal or diagnosed with MCI or dementia. Volumetric magnetic resonance imaging (MRI) measures of total brain volume, white matter hyperintensity volume, and hippocampal volume along with age, education, and gender were evaluated as predictors of episodic memory. WMH were found to influence both episodic memory and executive functioning independently of other variables. The influence WMH on episodic memory was mediated by executive functioning and was completely eliminated when the interaction between executive functioning and hippocampal volume was entered in the regression model. The results indicate that executive functioning mediates the effects of WMH on episodic memory but that executive functioning and hippocampal volume can also interact such that executive functioning can exacerbate or ameliorate the influence of hippocampal volume on episodic memory.

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“…Previous studies have demonstrated there is an association between WMSA burden and the rate of cognitive decline in MCI and AD individuals (Wolf et al 2000; Smith et al 2008; Tosto et al 2014). Additionally, the notion of differing levels of WM damage (Maillard et al 2013), particularly a penumbra encircling a central damage region, have been addressed before (Maillard et al 2014; Viswanathan 2014), and there is an extensive body of literature of the heterogeneous histological profiles of WM lesions that appear similar on MRI (Young et al 2008; Erten-Lyons et al 2013; Gouw et al 2011).…”

Section: Discussionmentioning

confidence: 96%

“…Little is known, however, about the development and time course of WM tissue damage in patients transitioning from normal cognition to dementia. Additionally, little is known regarding the degree to which WMSAs contribute to different states of cognitive decline—for example, whether WMSAs are associated with conversion from a cognitively healthy status to mild cognitive impairment (MCI), or from MCI to dementia such as Alzheimer's disease (AD) (Smith et al 2008; Wolf et al 2000; Medina et al 2006; DeCarli et al 1996). …”

Section: Introductionmentioning

confidence: 99%

White matter signal abnormality quality differentiates mild cognitive impairment that converts to Alzheimer's disease from nonconverters

Lindemer

Salat

Smith

et al. 2015

Neurobiology of Aging

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The objective of this study was to assess how longitudinal change in the quantity and quality of white matter signal abnormalities (WMSAs) contributes to the progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD). The Mahalanobis distance of WMSA from normal-appearing white matter using T1-, T2-, and PD-weighted MRI was defined as a quality measure for WMSA. Cross-sectional analysis of WMSA volume in 104 cognitively healthy older adults, 116 individuals with mild cognitive impairment who converted to AD within 3 years (MCI-C), 115 individuals with MCI that did not convert in that time (MCI-NC), and 124 individuals with AD from the Alzheimer's Disease Neuroimaging Initiative (ADNI) revealed that WMSA volume was substantially greater in AD relative to the other groups, but did not differ between MCI-NC and MCI-C. Longitudinally, MCI-C exhibited faster WMSA quality progression but not volume compared to matched MCI-NC beginning eighteen months prior to MCI-C conversion to AD. The strongest difference in rate of change was seen in the time period starting 6 months before MCI-C conversion to AD and ending 6 months after conversion (p < 0.001). The relatively strong effect in this time period relative to AD conversion in the MCI-C was similar to the relative rate of change in hippocampal volume, a traditional imaging marker of AD pathology. These data demonstrate changes in white matter tissue properties that occur within WMSA in individuals with MCI that will subsequently obtain a clinical diagnosis of AD within 18 months. Individuals with AD have substantially greater WMSA volume than all MCI suggesting that there is a progressive accumulation of WMSA with progressive disease severity, and that quality change predates changes in this total volume. Given the timing of the changes in WMSA tissue quality relative to the clinical diagnosis of AD, these findings suggest that WMSAs are a critical component for this conversion and are a critical component of this clinical syndrome.

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Do white matter changes contribute to the subsequent development of dementia in patients with mild cognitive impairment? A longitudinal study

Cited by 101 publications

References 51 publications

Tau Pathology and Parietal White Matter Lesions Have Independent but Synergistic Effects on Early Development of Alzheimer's Disease

Tau Pathology and Parietal White Matter Lesions Have Independent but Synergistic Effects on Early Development of Alzheimer's Disease

Executive function mediates effects of white matter hyperintensities on episodic memory

White matter signal abnormality quality differentiates mild cognitive impairment that converts to Alzheimer's disease from nonconverters

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