Diffusion Tensor Imaging Predictors of Episodic Memory Decline in Healthy Elders at Genetic Risk for Alzheimer’s Disease

Lancaster, Melissa A.; Seidenberg, Michael; Smith, J. Carson; Nielson, Kristy A.; Woodard, John L.; Durgerian, Sally; Rao, Stephen M.

doi:10.1017/s1355617716000904

Cited by 27 publications

(24 citation statements)

References 84 publications

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“…DTI studies have similarly reported that altered medial temporal lobe microstructure predicts memory decline ( Lancaster et al, 2016 ; L. Zhuang et al, 2012 ), is sensitive to MCI and correlates with cognitive function ( Fellgiebel et al, 2004 ; Hong et al, 2013 ; Kantarci et al, 2001 ). Our findings add to this literature by localizing the strongest associations between altered microstructure and cognitive decline to the hippocampus and entorhinal cortex.…”

Section: Discussionmentioning

confidence: 99%

“…However, evidence from diffusion MRI, which estimates fine architectural features from the diffusion properties within tissue, suggests that white matter degeneration may precede gray matter atrophy in AD ( Agosta et al, 2011 ; Amlien and Fjell, 2014 ; Fletcher et al, 2013 ; L. Zhuang et al, 2012 ). Both gray and white matter microstructure, measured with diffusion tensor imaging (DTI), track disease progression ( Kitamura et al, 2013 ; Nowrangi et al, 2013 ), predict cognitive decline and clinical conversion ( Douaud et al, 2013 ; Fletcher et al, 2013 ; Lancaster et al, 2016 ; Mielke et al, 2012 ; L. Zhuang et al, 2012 ), and correlate with neuropathological burden along the AD continuum ( Kantarci et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

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Microstructural brain changes track cognitive decline in mild cognitive impairment

Reas

Hagler

White

et al. 2018

NeuroImage: Clinical

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Improved characterization of the microstructural brain changes occurring in the early stages of Alzheimer's disease may permit more timely disease detection. This study examined how longitudinal change in brain microstructure relates to cognitive decline in aging and prodromal Alzheimer's disease. At baseline and two-year follow-up, 29 healthy controls and 21 individuals with mild cognitive impairment or mild Alzheimer's disease underwent neuropsychological evaluation and restriction spectrum imaging (RSI). Microstructural change in the hippocampus, entorhinal cortex, and white matter tracts previously shown to be vulnerable to Alzheimer's disease, was compared between healthy controls and impaired participants. Partial correlations and stepwise linear regressions examined whether baseline RSI metrics predicted subsequent cognitive decline, or change in RSI metrics correlated with cognitive change. In medial temporal gray and white matter, restricted isotropic diffusion and crossing fibers were lower, and free water diffusion was higher, in impaired participants. Restricted isotropic diffusion in the hippocampus declined more rapidly for cognitively impaired participants. Baseline hippocampal restricted isotropic diffusion predicted cognitive decline, and change in hippocampal and entorhinal restricted isotropic diffusion correlated with cognitive decline. Within controls, changes in white matter restricted oriented diffusion and crossing fibers correlated with memory decline. In contrast, there were no correlations between rates of cortical atrophy and cognitive decline in the full sample or within controls. Changes in medial temporal lobe microarchitecture were associated with cognitive decline in prodromal Alzheimer's disease, and these changes were distinct from microstructural changes in normal cognitive aging. RSI metrics of brain microstructure may hold value for predicting cognitive decline in aging and for monitoring the course of Alzheimer's disease.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Microstructural brain changes track cognitive decline in mild cognitive impairment

Reas

Hagler

White

et al. 2018

NeuroImage: Clinical

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“…Whereas amyloid-β levels rise before observable neurodegeneration, atrophy corresponds more closely with cognitive symptoms [6]. If white matter changes are more sensitive to early cognitive deficits than gray matter atrophy as has been suggested [7], they may better track cognitive decline than amyloid, though few studies have directly compared these biomarkers. The closer correspondence of structural changes than amyloid neuropathology to cognitive symptoms implies that, even if amyloid is an early disease trigger, the ensuing neurodegeneration may diverge along a distinct pathogenic avenue.…”

Section: Introductionmentioning

confidence: 99%

Associations Between Microstructure, Amyloid, and Cognition in Amnestic Mild Cognitive Impairment and Dementia

Reas

Hagler

Kuperman

et al. 2020

JAD

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BACKGROUND-Although amyloid-β and microstructural brain changes are both effective biomarkers of Alzheimer's disease, their independent or synergistic effects on cognitive decline are unclear. OBJECTIVE-To examine associations of amyloid-β and brain microstructure with cognitive decline in amnestic mild cognitive impairment and dementia. METHODS-Restriction spectrum imaging (RSI), CSF amyloid-β and longitudinal cognitive data were collected on 23 healthy controls and 13 individuals with mild cognitive impairment or mild Alzheimer's disease. Neurite density (ND) and isotropic free water diffusion (IF) were computed in fiber tracts and cortical regions of interest. We examined associations of amyloid-β with regional and whole-brain microstructure, and assessed whether microstructure mediates effects of amyloid-β on cognitive decline. RESULTS-Lower ND in limbic and association fibers and higher medial temporal lobe IF predicted baseline impairment and longitudinal decline across multiple cognitive domains. ND and IF predicted cognitive outcomes after adjustment for amyloid-β or whole-brain microstructure.

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“…A related debate in the literature concerns whether agerelated cognitive decline is due to alterations within specific white matter tracts or to global white matter changes occurring across the whole brain (Bennett and Madden 2014). Tractspecific effects have been observed across several cognitive domains (Kennedy and Raz 2009;Madden et al 2009;Zahr et al 2009;Ryan et al 2011;Voineskos et al 2012;Lövdén et al 2014;Bennett et al 2015;Cremers et al 2016;Lancaster et al 2016;Ly et al 2016), however, there are inconsistencies across studies regarding which tracts display significant relationships. In contrast, other researchers have found evidence in favor of a global effect (Grieve et al 2007;Penke et al 2010;Haász et al 2013;Kuznetsova et al 2016;Fjell et al 2017), which is consistent with the observation that white matter tracts generally show high correlations with one another (Penke et al 2010;Lövdén et al 2014;Cox et al 2016).…”

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confidence: 99%

Global White Matter Diffusion Characteristics Predict Longitudinal Cognitive Change Independently of Amyloid Status in Clinically Normal Older Adults

et al. 2018

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White matter degradation has been proposed as one possible explanation for age-related cognitive decline. In the present study, we examined 2 main questions: 1) Do diffusion characteristics predict longitudinal change in cognition independently or synergistically with amyloid status? 2) Are the effects of diffusion characteristics on longitudinal cognitive change tract-specific or global in nature? Cognitive domains of executive function, episodic memory, and processing speed were measured annually (mean follow-up = 3.93 ± 1.25 years). Diffusion tensor imaging and Pittsburgh Compound-B positron emission tomography were performed at baseline in 265 clinically normal older adults (aged 63-90). Tract-specific diffusion was measured as the mean fractional anisotropy (FA) for 9 major white matter tracts. Global diffusion was measured as the mean FA across the 9 white matter tracts. Linear mixed models demonstrated independent, rather than synergistic, effects of global FA and amyloid status on cognitive decline. After controlling for amyloid status, lower global FA was associated with worse longitudinal performance in episodic memory and processing speed, but not executive function. After accounting for global FA, none of the individual tracts predicted a significant change in cognitive performance. These findings suggest that global, rather than tract-specific, diffusion characteristics predict longitudinal cognitive decline independently of amyloid status.

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Diffusion Tensor Imaging Predictors of Episodic Memory Decline in Healthy Elders at Genetic Risk for Alzheimer’s Disease

Cited by 27 publications

References 84 publications

Microstructural brain changes track cognitive decline in mild cognitive impairment

Microstructural brain changes track cognitive decline in mild cognitive impairment

Associations Between Microstructure, Amyloid, and Cognition in Amnestic Mild Cognitive Impairment and Dementia

Global White Matter Diffusion Characteristics Predict Longitudinal Cognitive Change Independently of Amyloid Status in Clinically Normal Older Adults

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