Hippocampal atrophy but not white-matter changes predicts the long-term cognitive response to cholinesterase inhibitors in Alzheimer's disease.

Yu-Wen Cheng,Ting-Wen Cheng,Ya-Mei Lai,Ming-Jang Chiu,Ta-Fu Chen,Ya-Fang Chen,Mau-Sun Hua

doi:10.1186/s13195-015-0155-9

Abstract

IntroductionThis study aimed to investigate the feasibility of predicting the long–term effects of cholinesterase inhibitors (ChEI) with common clinical neuroimaging parameters of Alzheimer’s disease, including medial temporal lobe atrophy (MTA) and white matter hyperintensity (WMH).MethodA cohort of 353 patients with very mild to moderate Alzheimer’s disease received cholinesterase inhibitors and were followed for a median of 46.6 months. Baseline clinical data, including age, educational level, Clinical Dementia Rating (CDR), Taiwanese Mental State Examination (TMSE), and visual scoring for MTA and WMH were tested as possible predictive factors that influence the survival from a TMSE decline of at least 3 points.ResultsDuring the follow-up period, 162(46 %) patients had a significant TMSE decline. Patients with age-adjusted prominent MTA had a significantly shorter TMSE-decline free interval than those without (43.4 ± 4.5 months vs. 68.2 ± 9.5 months, log rank test p-value =0.001). However, the severity of WMH does not significantly influence cognitive outcomes. Cox regression analysis identified that younger age at the time of starting ChEI (p < 0.0005) and higher total MTA scores (p = 0.002) predict a more rapid TMSE decline under ChEI therapy.ConclusionsYounger age at the time of starting ChEI and higher visual scoring of MTA may imply a more advanced Alzheimer’s pathology. WMH load is not a prognostic indicator of treatment response to ChEI.

Highlights

This study aimed to investigate the feasibility of predicting the long–term effects of cholinesterase inhibitors (ChEI) with common clinical neuroimaging parameters of Alzheimer’s disease, including medial temporal lobe atrophy (MTA) and white matter hyperintensity (WMH)
We found that a higher total WMH score, higher educational level, and lower Taiwanese Mental State Examination (TMSE) are associated with a higher total MTA score (Table 3)
ChEI therapy, defined by a longer TMSE decline-free survival; (2) the severity of WMH does not significantly affect the TMSE decline-free survival; (3) a higher total MTA score was associated with a higher WMH score, higher educational level, and a lower baseline TMSE; and (4) a higher total WMH score was associated with older age, higher total MTA score, and higher baseline Clinical Dementia Rating (CDR)

Summary

Introduction

This study aimed to investigate the feasibility of predicting the long–term effects of cholinesterase inhibitors (ChEI) with common clinical neuroimaging parameters of Alzheimer’s disease, including medial temporal lobe atrophy (MTA) and white matter hyperintensity (WMH). Previous studies have shown that the degree of medial temporal atrophy (MTA) was associated with the risk of progression from mild cognitive impairment (MCI) to AD [10,11,12], the disease stage [13], and the rate of cognitive decline [14]. The association between MTA and the long-term therapeutic response to ChEI is not well established. Another neuroimaging characteristic is the white matter hyperintensity (WMH), which is viewed by some researchers as an indicator of the underlying vascular burden that

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