White matter changes in preclinical Alzheimer's disease: a magnetic resonance imaging-diffusion tensor imaging study on cognitively normal older people with positive amyloid β protein 42 levels

Molinuevo, José Luís; Ripollés, Pablo; Simó, Marta; Lladó, Albert; Olives, Jaume; Balasa, Mircea; Antonell, Anna; Rodrı́guez-Fornells, Antoni; Rami, Lorena

doi:10.1016/j.neurobiolaging.2014.05.027

Cited by 75 publications

(89 citation statements)

References 66 publications

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“…A recent study compared cognitively normal subjects with low and normal CSF Ab 42 and found increased DA without changes in the remaining indices, possibly indicating axonal damage with preservation of white matter integrity in presymptomatic phases of AD. 22 However, these findings were in different regions of interest (ROIs) and not within WMHs. Further, it has previously been suggested that DA is one of the first DTI changes observed in AD.…”

Section: Discussionmentioning

confidence: 94%

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White matter hyperintensity microstructure in amyloid dysmetabolism

Kalheim

Bjørnerud

Fladby

et al. 2016

J Cereb Blood Flow Metab

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Accumulating evidence suggests associations between cerebrovascular disease (CVD) and Alzheimer's disease (AD). White matter hyperintensities of presumed vascular origin (WMHs) are increased in subjects with mild cognitive impairment (MCI) and AD, but the exact pathomechanistic link is unknown. The current study investigated effects of amyloid dysmetabolism on the microstructure of WMHs in subjects with MCI or subjective cognitive decline (N ¼ 51), dichotomized according to pathological or normal levels of amyloid-b peptide (Ab 42 ) in cerebrospinal fluid (CSF). Thirtyone subjects with low CSF Ab 42 (Abþ) and 20 subjects with normal CSF Ab 42 (AbÀ) were assessed with magnetic resonance diffusion tensor imaging (DTI), and fractional anisotropy (FA), radial diffusivity (DR), axial diffusivity (DA), and mean diffusivity (MD) were determined. There were no significant differences in WMH volume or distribution between the groups, and neither age nor WMH volume had significant impact on the DTI indices. Nevertheless, there were significantly higher DA, DR, and MD in WMHs in Abþ relative to AbÀ; however, no differences in FA were found. The present results suggest that amyloid accumulation is associated with impaired structural integrity (e.g. relating to more extensive demyelination and loss of axons) in WMHs putatively adding to effects of ischemia.

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Section: Discussionmentioning

confidence: 94%

“…19,20 Further, WMHs have been associated with decreased FA, 21 and amyloid-positive subjects have presented with increased DA. 22 However, to our knowledge, no studies have evaluated the effects of amyloid metabolism on WMHs diffusion properties.…”

Section: Introductionmentioning

confidence: 99%

White matter hyperintensity microstructure in amyloid dysmetabolism

Kalheim

Bjørnerud

Fladby

et al. 2016

J Cereb Blood Flow Metab

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“…Other recent studies examined white matter changes in asymptomatic individuals showing biomarker evidence of amyloid or tau pathology (Bendlin et al, 2012;Chao et al, 2013;Gold et al, 2014;Kantarci et al, 2014;Molinuevo et al, 2014;Racine et al, 2014;Stenset et al, 2011). These cross-sectional studies of at-risk populations are now increasingly being complemented by longitudinal follow-up studies that allow relating the detected imaging abnormalities to future clinical outcomes Fletcher et al, 2013;Mielke et al, 2012;Zhuang et al, 2012).…”

Section: Structural Disconnection In the Course Of Admentioning

confidence: 99%

Measuring Cortical Connectivity in Alzheimer’s Disease as a Brain Neural Network Pathology: Toward Clinical Applications

Teipel

Grothe

Zhou

et al. 2016

J Int Neuropsychol Soc

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Objectives: The objective was to review the literature on diffusion tensor imaging as well as resting-state functional magnetic resonance imaging and electroencephalography (EEG) to unveil neuroanatomical and neurophysiological substrates of Alzheimer's disease (AD) as a brain neural network pathology affecting structural and functional cortical connectivity underlying human cognition. Methods: We reviewed papers registered in PubMed and other scientific repositories on the use of these techniques in amnesic mild cognitive impairment (MCI) and clinically mild AD dementia patients compared to cognitively intact elderly individuals (Controls). Results: Hundreds of peer-reviewed (cross-sectional and longitudinal) papers have shown in patients with MCI and mild AD compared to Controls (1) impairment of callosal (splenium), thalamic, and anterior-posterior white matter bundles; (2) reduced correlation of resting state blood oxygen level-dependent activity across several intrinsic brain circuits including default mode and attention-related networks; and (3) abnormal power and functional coupling of resting state cortical EEG rhythms. Clinical applications of these measures are still limited. Conclusions: Structural and functional (in vivo) cortical connectivity measures represent a reliable marker of cerebral reserve capacity and should be used to predict and monitor the evolution of AD and its relative impact on cognitive domains in pre-clinical, prodromal, and dementia stages of AD. (JINS, 2016, 22, 138-163)

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“…Some of these studies also demonstrated strong correlation with widely-used clinical measures [20,23,24].…”

Section: Introductionmentioning

confidence: 81%

White Matter Abnormalities Track Disease Progression in PSEN1 Autosomal Dominant Alzheimer’s Disease

Sánchez‐Valle

Monté

Sala‐Llonch

et al. 2016

JAD

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Abstract. PSEN1 mutations are the most frequent cause of autosomal dominant Alzheimer's disease (ADAD), and show nearly full penetrance. There is presently increasing interest in the study of biomarkers that track disease progression in order to test therapeutic interventions in ADAD. We used white mater (WM) volumetric characteristics and diffusion tensor imaging (DTI) metrics to investigate correlations with the normalized time to expected symptoms onset (relative age ratio) and group differences in a cohort of 36 subjects from PSEN1 ADAD families: 22 mutation carriers, 10 symptomatic (SMC) and 12 asymptomatic (AMC), and 14 non-carriers (NC). Subjects underwent a 3T MRI. WM morphometric data and DTI metrics were analyzed. We found that PSEN1 MC showed significant negative correlation between fractional anisotropy (FA) and the relative age ratio in the genus and body of corpus callosum and corona radiate (p < 0.05 Family-wise error correction (FWE) at cluster level) and positive correlation with mean diffusivity (MD), axial diffusivity (AxD), and radial diffusivity (RD) in the splenium of corpus callosum. SMC presented WM volume loss, reduced FA and increased MD, AxD, and RD in the anterior and posterior corona radiate, corpus callosum (p < 0.05 FWE) compared with NC. No significant differences were observed between AMC and NC in WM volume or DTI measures. These findings suggest that the integrity of the WM deteriorates linearly in PSEN1 ADAD from the early phases of the disease; thus DTI metrics might be useful to monitor the disease progression. However, the lack of significant alterations at the preclinical stages suggests that these indexes might not be good candidates for early markers of the disease.

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White matter changes in preclinical Alzheimer's disease: a magnetic resonance imaging-diffusion tensor imaging study on cognitively normal older people with positive amyloid β protein 42 levels

Cited by 75 publications

References 66 publications

White matter hyperintensity microstructure in amyloid dysmetabolism

White matter hyperintensity microstructure in amyloid dysmetabolism

Measuring Cortical Connectivity in Alzheimer’s Disease as a Brain Neural Network Pathology: Toward Clinical Applications

White Matter Abnormalities Track Disease Progression in PSEN1 Autosomal Dominant Alzheimer’s Disease

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