White Matter Changes May Precede Gray Matter Loss in Elderly with Subjective Memory Impairment

Abstract

Background/Aims: A limited number of studies addressed MRI-based neurodegenerative changes in subjective memory impairment (SMI). We investigated changes in white matter (WM) microstructures as well as gray matter (GM) macrostructures in subjects with SMI of high and low risk for progression. Methods: A modeling scale (score range, 0-6) developed for prediction of SMI progression was used to divide SMI subjects (n = 46) into two groups: a high risk of progression (score ≥3; n = 19) and a low risk of progression (score ≤2; n = 27). Cross-sectional comparisons were performed using a region-of-interest-based diffusion tensor imaging (DTI) analysis, cortical thickness analysis, and hippocampal volumetry. Results: The high-risk group had more microstructural disruption shown by lower fractional anisotropy in the hippocampus, parahippocampal gyrus, supramarginal gyrus, and parts of frontotemporal lobes. On the other hand, GM macrostructural changes did not differ between the groups and were not associated with modeling scale scores. Conclusion: SMI subjects with a high risk of progression had more WM microstructural disruption than those with a low risk, and the changes were not explained by GM atrophy. Our findings suggest that the degree of microstructural alterations in SMI may be distinctive according to the risk factors and may precede GM atrophy.

Neuroimaging advances regarding subjective cognitive decline in preclinical Alzheimer’s disease

“…Another investigation categorized individuals with SCD into a high-risk group and a low-risk group based on age, ApoE genotype, K-MMSE recall score and the Seoul Verbal Learning Test. The high-risk group showed more severe microstructural disruptions with reduced FA in the tracts connecting the hippocampus, parahippocampal gyrus, supramarginal gyrus and parts of the frontotemporal lobes [ 118 ].…”

“…Research combining MRI volumetric and DTI measures suggested that individuals with SCD showed a lower entorhinal cortical volume, lower FA and higher MD in the hippocampal body and entorhinal WM [ 78 ]. According to another study [ 118 ], individuals with SCD with a high risk of progression had more severe WM disruption than the low-risk SCD group but no evident gray matter atrophy. Thus, relatively high-risk SCD may predict an underlying microstructural disruption in the WM that precedes gray matter atrophy during AD progression.…”

“…Lower volume of the dentate gyres associates with poorer memory performance. Hong et al (2016) [ 118 ] Memory clinic consultation T1 MRI DTI Cross-sectional Low risk: n = 27 (62.1 ± 7.1) High risk: n = 19 (67.1 ± 6.5) The high-risk group showed lower FA in the hippocampus, parahippocampal gyrus, supramaiginal gyrus and parts of fronto-temporal lobes, but no gray matter atrophy. Jung et al (2016) [ 121 ] Memory clinic consultation T1 MRI Cross-sectional SMI: n=612(64.9 ± 6.9) Individuals with different subtype atrophy showed difference in age, gender, vascular risk factors and depression.…”

Parietal white matter lesions in Alzheimer’s disease are associated with cortical neurodegenerative pathology, but not with small vessel disease

“…These changes include reduced integrity in white matter tracts connected to the medial temporal lobe (MTL) [ 2 , 31 ], the cingulum and in the tracts of the temporo-parietal regions such as the superior longitudinal fasciculus [ 1 , 7 ]. These changes in white matter structure have been directly associated with Wallerian degeneration independent of cortical atrophy [ 3 , 7 , 28 ]. Moreover, AD cases with severe cortical AD pathology and severe WML exhibited only minimal SVD pathology at post-mortem examination [ 17 , 40 ], indicating that SVD was not the primary cause of WML in these cases.…”

Multicenter Tract-Based Analysis of Microstructural Lesions within the Alzheimer’s Disease Spectrum: Association with Amyloid Pathology and Diagnostic Usefulness

“…SCD cases have a two-fold increased risk to develop dementia and a six-fold increased risk to develop MCI over on average four years of clinical follow-up compared with cognitively normal people without subjective cognitive complaints [11]. Several studies found significant differences in DTI parameters, such as fractional anisotropy or mean diffusivity, in SCD cases compared with controls [12][13][14][15]. Studies on the diagnostic utility of DTI markers, however, for the discrimination between SCD cases and controls are still scarce.…”