Suboptimal Baseline Serum Vitamin B12 Is Associated With Cognitive Decline in People With Alzheimer's Disease Undergoing Cholinesterase Inhibitor Treatment.

Hsiao Shan Cho,Li Kai Huang,Lung Chan,Yao Tung Lee,Chien Tai Hong

doi:10.3389/fneur.2018.00325

Abstract

Cholinesterase inhibitors (ChEIs) are the mainstream treatment for delaying cognitive decline in Alzheimer's disease (AD). Low vitamin B12 is associated with cognitive dysfunction, and its supplementation has been applied as the treatment for certain types of reversible dementia. The present study hypothesized that baseline serum vitamin B12 is associated with the deterioration of cognitive function in people with AD undergoing ChEI treatment. Between 2009 and 2016, medical records from 165 Taiwanese with mild to moderate AD who underwent ChEI treatment for at least 2 years were reviewed. Their baseline serum vitamin B12 levels were measured before treatment initiation. Their cognitive function was assessed using the Mini-Mental State Examination (MMSE) and Cognitive Abilities Screening Instrument (CASI). Student's t test and multivariable logistic regression were used to analyze the association between cognitive decline and vitamin B12 level. Statistical analyses were performed using SPSS 19.0. Overall, 122 participants were women. Their median age was 76 years (ranging from 54 to 91). For people with optimal baseline vitamin B12 (above the median level of 436 ng/L), the rates of MMSE and CASI decline were 0.78 ± 1.28 and 2.84 ± 4.21 per year, respectively, which were significantly slower than those with suboptimal vitamin B12 (1.42 ± 1.67 and 4.94 ± 5.88 per year; p = 0.007 and 0.009, respectively). After adjustment for age, sex, education level, hypertension, diabetes, history of stroke, and baseline cognitive function, the baseline serum vitamin B12 level was negatively associated with MMSE and CASI decline. Suboptimal baseline serum vitamin B12 level is associated with cognitive decline in people with AD undergoing ChEI treatment.

Highlights

Alzheimer’s disease (AD) is the most common cause of dementia
After adjustment for age, sex, education level, hypertension, diabetes, history of stroke, and baseline cognitive function, the baseline serum vitamin B12 level was negatively associated with Mini–Mental State Examination (MMSE) and Cognitive Abilities Screening Instrument (CASI) decline
Suboptimal baseline serum vitamin B12 level is associated with cognitive decline in people with AD undergoing cholinesterase inhibitors (ChEIs) treatment

Summary

Introduction

Alzheimer’s disease (AD) is the most common cause of dementia. Estimates have revealed that in 2050, the number of people with AD aged 65 years and older will be triple [1]. The most effective symptomatic pharmacological treatment for AD is cholinesterase inhibitors (ChEIs), which delay the progress of cognitive dysfunction [2]. A previous intellectual occupation, healthier lifestyles, being married and not living alone, a higher degree of autonomy, and lower degree of brain atrophy at baseline were associated with better response to ChEI [3]. The genotype of apolipoprotein E (ApoE), a cholesterol-transporting enzyme is strongly associated with AD. Whether ApoE genotype affects the response to ChEI in people with AD is controversial. It had been demonstrated that ApoE ε4 allele carriers were poor responders to tacrine [4]; other studies revealed that this detrimental genotype carriers exhibited better response to donepezil [5, 6]. Evidence from several prospective, randomized, placebo-controlled trials with large samples were consistent with that ApoE was not a good predictor of response to ChEIs [7,8,9,10]

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