Abstract

IntroductionCognitive performance in patients with Alzheimer's dementia (AD) and mild cognitive impairment (MCI) has been reported to be related to hippocampal atrophy and microstructural changes in white matter (WM). We aimed to predict the neurocognitive functions of patients with MCI or AD using hippocampal volumes and diffusion tensor imaging (DTI) metrics via partial least squares regression (PLSR).MethodsA total of 148 elderly female subjects were included: AD (n = 49), MCI (n = 66), and healthy controls (n = 33). Twenty‐four hippocampal subfield volumes and the average values for fractional anisotropy (FA) and mean diffusivity (MD) of 48 WM tracts were used as predictors, CERAD‐K total scores, scores of CERAD‐K 7 cognitive subdomains and K‐GDS were used as dependent variables in PLSR.ResultsRegarding MCI patients, DTI metrics such as the MD values of the left retrolenticular part of the internal capsule and left fornix (cres)/stria terminalis were significant predictors, while hippocampal subfield volumes, like the left CA1 and hippocampal tail, were main contributors to cognitive function in AD patients, although global FA/MD values were also strong predictors. The 10‐fold cross‐validation and stricter 300‐iteration tests proved that global cognition measured by the CERAD‐K total scores and the scores of several CERAD‐K subdomains can be reliably predicted using the PLSR models.ConclusionsOur findings indicate different structural contributions to cognitive function in MCI and AD patients, implying that diffuse WM microstructural changes may precede hippocampal atrophy during the AD neurodegenerative process.

Highlights

  • Cognitive performance in patients with Alzheimer’s dementia (AD) and mild cognitive impairment (MCI) has been reported to be related to hippocampal atrophy and microstructural changes in white matter (WM)

  • We hypothesized that several variables among hippocampal subfield volumes and diffusion tensor imaging (DTI) metrics, such as fractional anisotropy (FA) and mean diffusivity (MD), might significantly contribute to the cognitive functions of both patients, but DTI measures might be more predictive for cognitive function in MCI patients compared to AD patients since microstructural changes in WM were considered to precede hippocampal atrophy

  • We found that cognitive function of MCI and AD patients can be predicted using partial least squares regression (PLSR) models in which the predictors are the hippocampal subfield volumes and DTI metrics (FA/MD)

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Summary

| INTRODUCTION

Alzheimer’s dementia (AD) usually progresses slowly for a decade or more before a diagnosis of dementia, and a mild cognitive impairment (MCI) is proposed to capture the prodromal stages of various etiologies of dementia, including AD. Molecular, functional, and structural biomarkers have been developed to accurately diagnose AD (Ishii, 2014) and to predict conversion from MCI to AD at an early time (Forlenza, Diniz, Teixeira, Stella, & Gattaz, 2013) Among these biomarkers, structural MRI is indispensable, and atrophy of the medial temporal lobe including the hippocampus is considered as a valid diagnostic marker (Frisoni, Fox, Jack, Scheltens, & Thompson, 2010) and as a risk factor of conversion to AD (Grundman et al, 2002). Partial least squares regression (PLSR) combines features from and generalizes principal component analysis and multiple linear regression (Abdi, 2010), and it is useful when we need to predict a set of dependent variables from numerous, highly collinear independent variables or predictors (Tobias, 1995). We hypothesized that several variables among hippocampal subfield volumes and DTI metrics, such as FA and MD, might significantly contribute to the cognitive functions of both patients, but DTI measures might be more predictive for cognitive function in MCI patients compared to AD patients since microstructural changes in WM were considered to precede hippocampal atrophy

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