Higher Blood Vitamin C Levels are Associated with Reduction of Apolipoprotein E E4-related Risks of Cognitive Decline in Women: The Nakajima Study

Noguchi‐Shinohara, Moeko; Abe, Chiemi; Yuki-Nozaki, Sohshi; Dohmoto, Chiaki; Mori, Akira; Hayashi, Kôji; Shibata, Syutaro; Ikeda, Yoshihisa; Sakai, Kenji; Iwasa, Kazuo; Yokogawa, Masami; Ishimiya, Mai; Yokoji, Hidehiro; Komai, Koichiro; Nakamura, Hiroyuki; Yamada, Masahito

doi:10.3233/jad-170971

Cited by 24 publications

(18 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As demonstrated in a previous study with an Alzheimer’s disease model [20], ascorbic acid co-treatment ameliorates D-gal-induced memory impairment. Noguchi-Shinohara et al (2018) recently found that a high blood level of ascorbic acid is associated with the amelioration of apolipoprotein E E4-related cognitive decline in elderly women [52]. Because ascorbic acid has a low toxicity and is a low-cost compound, it could be one of the representative antioxidants that are effective in delaying the onset and progression of Alzheimer’s disease in humans [53].…”

Section: Discussionmentioning

confidence: 99%

Ascorbic Acid Mitigates D-galactose-Induced Brain Aging by Increasing Hippocampal Neurogenesis and Improving Memory Function

Nam

Seo

et al. 2019

Nutrients

View full text Add to dashboard Cite

Ascorbic acid is essential for normal brain development and homeostasis. However, the effect of ascorbic acid on adult brain aging has not been determined. Long-term treatment with high levels of D-galactose (D-gal) induces brain aging by accumulated oxidative stress. In the present study, mice were subcutaneously administered with D-gal (150 mg/kg/day) for 10 weeks; from the seventh week, ascorbic acid (150 mg/kg/day) was orally co-administered for four weeks. Although D-gal administration alone reduced hippocampal neurogenesis and cognitive functions, co-treatment of ascorbic acid with D-gal effectively prevented D-gal-induced reduced hippocampal neurogenesis through improved cellular proliferation, neuronal differentiation, and neuronal maturation. Long-term D-gal treatment also reduced expression levels of synaptic plasticity-related markers, i.e., synaptophysin and phosphorylated Ca2+/calmodulin-dependent protein kinase II, while ascorbic acid prevented the reduction in the hippocampus. Furthermore, ascorbic acid ameliorated D-gal-induced downregulation of superoxide dismutase 1 and 2, sirtuin1, caveolin-1, and brain-derived neurotrophic factor and upregulation of interleukin 1 beta and tumor necrosis factor alpha in the hippocampus. Ascorbic acid-mediated hippocampal restoration from D-gal-induced impairment was associated with an enhanced hippocampus-dependent memory function. Therefore, ascorbic acid ameliorates D-gal-induced impairments through anti-oxidative and anti-inflammatory effects, and it could be an effective dietary supplement against adult brain aging.

show abstract

Section: Discussionmentioning

confidence: 99%

Ascorbic Acid Mitigates D-galactose-Induced Brain Aging by Increasing Hippocampal Neurogenesis and Improving Memory Function

Nam

Seo

et al. 2019

Nutrients

View full text Add to dashboard Cite

show abstract

“…Alzheimer's disease, which accounts for over half of all dementia, occurs at a greater frequency in women versus men. A study shows the higher vitamin C level reduce the risk of cognitive decline in women with APOE4 and men without APOE4 (Noguchi-Shinohara et al, 2018). Factors related to the female endocrine system are assumed to be associated with the differences observed according to the sex.…”

Section: Discussionmentioning

confidence: 99%

Sex Differences in the Relationship of Serum Vitamin B1 and B12 to Dementia Among Memory Clinic Outpatients in Japan

Miki

Kinno

Ochiai

et al. 2021

Front. Aging Neurosci.

View full text Add to dashboard Cite

Dementia and cognitive impairment are considered to be one of the biggest social and medical problems. While there is a definite relationship between vitamin B and cognitive decline, this has yet to be fully assessed with regard to sex differences. Thus, the present study investigated the relationship of vitamin B1 or vitamin B12 with dementia in accordance with the sex in 188 patients who visited the Memory Clinic at Showa University Hospital in Japan from March 2016 to March 2019. Cognitive function was tested by the Japanese version of the Mini-Mental State Examination (MMSE) and Hasegawa Dementia Scale-Revised (HDS-R). Blood tests were performed to measure the vitamin levels. Logistic regression analysis was used to calculate the odds ratio (OR) for dementia and the 95% confidence interval (CI). Compared to the highest vitamin group (third tertile), the lowest vitamin group (first tertile) exhibited a significantly increased OR for dementia defined by MMSE for vitamin B1 (OR:3.73, 95% CI:1.52–9.16) and vitamin B12 (2.97, 1.22–7.28) among women. In contrast, vitamin levels were not significantly associated with dementia determined by MMSE in men. These findings were similar even when dementia was defined by HDS-R. The present study suggests that vitamin B1 plays a role in preventing development of dementia in women. Future longitudinal studies will need to be undertaken in order to examine whether decreasing vitamin levels occur before or after cognitive impairment, and whether maintaining a higher vitamin level can prevent a worsening of cognitive function and the development of dementia.

show abstract

“…As a part of the Nakajima study, this study involved individuals aged 65 years or older with normal cognitive function during the 2006–2008 baseline survey. The study design has been described in detail previously [ 8 , 24 – 26 ]. We assessed participants’ cognitive status using the Mini-Mental State Examination (MMSE) [ 27 ] and Clinical Dementia Rating [ 28 – 30 ].…”

Section: Methodsmentioning

confidence: 99%

“…APOE4 risk of cognitive decline may be modified by interaction with other factors; however, the role of risk modifiers or interacting factors is not well understood. In our previous longitudinal study, we found that high serum vitamin C (VC) levels during normal cognition reduce APOE4-associated risk of cognitive decline, especially in women [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Effects of functional variants of vitamin C transporter genes on apolipoprotein E E4-associated risk of cognitive decline: The Nakajima study

et al. 2021

Self Cite

View full text Add to dashboard Cite

Apolipoprotein E E4 (APOE4) is a risk factor for cognitive decline. A high blood vitamin C (VC) level reduces APOE4-associated risk of developing cognitive decline in women. In the present study, we aimed to examine the effects of functional variants of VC transporter genes expressed in the brain (SLC2A1, SLC2A3, and SLC23A2) on APOE4-associated risk of developing cognitive decline. This case–control study involved 393 Japanese subjects: 252 cognitively normal and 141 cognitively impaired individuals (87 mild cognitive impairment and 54 dementia). Database searches revealed that rs1279683 of SLC23A2, and rs710218 and rs841851 of SLC2A1 are functional variants that are significantly associated with the altered expression of the respective genes and genotyped as three single nucleotide variants (SNVs). When stratified by SNV genotype, we found a significant association between APOE4 and cognitive decline in minor allele carriers of rs1279683 (odds ratio [OR] 2.02, 95% CI, 1.05–3.87, p = 0.035) but not in the homozygote carriers of the major allele. Significant associations between APOE4 and cognitive decline were also observed in participants with major allele homozygotes of rs710218 (OR 2.35, 95% CI, 1.05–5.23, p = 0.037) and rs841851 (OR 3.2, 95% CI, 1.58–6.46, p = 0.0012), but not in minor allele carriers of the respective SNVs. In contrast, the three functional SNVs showed no significant effect on cognitive decline. Our results imply that functional SNVs of VC transporter genes can affect APOE4-associated risk of developing cognitive decline via altered VC levels in the brain.

show abstract

Higher Blood Vitamin C Levels are Associated with Reduction of Apolipoprotein E E4-related Risks of Cognitive Decline in Women: The Nakajima Study

Abstract: Our results demonstrate significant beneficial effects of vitamins C and E in reducing the risk of cognitive decline in women with APOE E4 and men without APOE E4, respectively.

Cited by 24 publications

References 39 publications

Ascorbic Acid Mitigates D-galactose-Induced Brain Aging by Increasing Hippocampal Neurogenesis and Improving Memory Function

Ascorbic Acid Mitigates D-galactose-Induced Brain Aging by Increasing Hippocampal Neurogenesis and Improving Memory Function

Sex Differences in the Relationship of Serum Vitamin B1 and B12 to Dementia Among Memory Clinic Outpatients in Japan

Effects of functional variants of vitamin C transporter genes on apolipoprotein E E4-associated risk of cognitive decline: The Nakajima study

Contact Info

Product

Resources

About