Ascorbic Acid and Rates of Cognitive Decline in Alzheimer's Disease

Department of Neurology, Oregon Health & Science University, Portland, OR, USA.
Journal of Alzheimer's disease: JAD (Impact Factor: 4.15). 02/2009; 16(1):93-8. DOI: 10.3233/JAD-2009-0923
Source: PubMed


The brain maintains high levels of ascorbic acid (AA) despite a concentration gradient favoring diffusion from brain to peripheral tissues. Dietary antioxidants, including AA, appear to modify the risk of Alzheimer's disease (AD). The objective of this study was to test the hypothesis that neurodegeneration in AD is modified by brain levels of AA. Thirty-two patients with mild to moderate AD participated in a biomarker study involving standardized clinical assessments over one year. Cerebrospinal fluid (CSF) and serum were collected at baseline for AA and albumin content. Cognitive measures were collected at baseline and one year. CSF and plasma AA failed to predict cognitive decline independently, however, CSF: plasma AA ratio did. After adding CSF Albumin Index (an established marker of blood-brain barrier integrity) to the regression models the effect of CSF: plasma AA ratio as a predictor of cognitive decline was weakened. CSF: plasma AA ratio predicts rate of decline in AD. This relationship may indicate that the CSF: plasma AA ratio is an index of AA availability to the brain or may be an artifact of a relationship between blood-brain barrier impairment and neurodegeneration.

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Available from: Hiroko Hayama Dodge, Sep 30, 2015
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    • "As noted in Table  1, the mean plasma concentration in the Alzheimer’s patients was 31% lower than in age and sex-matched controls, presumably due to less AA in their dietary intake. In a separate uncontrolled study of 32 Alzheimer’s patients, Bowman et al. found a mean CSF/plasma ratio of 4.0 ± 0.3 (SEM)– confirming the findings summarized in Table  1[37]. Collectively, these data provide no support for abnormal AA transport function in CP of elderly or Alzheimer’s patients. "
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    ABSTRACT: We and other investigators have postulated deterioration of essential choroid plexus (CP) functions in some elderly and especially Alzheimer's disease patients based on apparent anatomical, histological and pathological changes in CP. We have termed this putative phenomenon CP failure. By focusing on four essential energy-requiring CP functions, specifically ascorbic acid (AA) and folate transport from blood into CSF, transthyretin synthesis and secretion into CSF, and electrolyte/acid--base balance in CSF, we were able to evaluate the hypothesis of CP failure by reviewing definitive human data. In both healthy elderly and Alzheimer's disease patients, the CP functions normally to transport AA and folates actively from blood into CSF, synthesize and secrete transthyretin into CSF, and maintain CSF acid--base balance and ion concentrations. These human CSF compositional data provide no support for the notion of CP failure in elderly humans and Alzheimer's disease patients.
    Fluids and Barriers of the CNS 09/2013; 10(1):28. DOI:10.1186/2045-8118-10-28
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    • "¼ 0.001) and plasma (P ¼ 0.002) and CSF (P ¼ 0.038) were lower in AD. All subjects were well-nourished and without vascular disease 18 Ctls (MMSE 27), 20 AD (MMSE 16) Women Age-matched (75–85 years) Cross sectional Bowman et al. [28] 32 41 6 30 129 6 52 4.0 6 1.6 Higher CSF: plasma AA ratio associated with slower cognitive decline over 1 year (age, gender, education, apoEe4, and cognitive function at baseline adjusted P ¼ 0.025). Interaction between CSF AA ratio and BBB integrity identified AD (MMSE 19 6 5) Men/women Mean age 71 years Prospective "
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    ABSTRACT: This narrative review appraises the human and animal studies implicating ascorbic acid (AA) in normal cognitive function and Alzheimer's disease. A research framework for how nutrition affects brain aging is proposed with emphasis on AA intake, status, metabolism, and transport into brain tissue. A final synopsis highlights areas for future research regarding AA nourishment and healthy brain aging.
    BioFactors 03/2012; 38(2):114-22. DOI:10.1002/biof.1002 · 4.59 Impact Factor
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    • "Furthermore, plasma levels of the antioxidant vitamin C are lower than normal in Alzheimer's patients, regardless of intake (Charlton et al., 2004; Riviere et al., 1998). Increased vitamin C intake from the diet or supplement form has been shown in some studies to lower the risk of developing Alzheimer's disease (Engelhart et al., 2002; Morris et al., 1998), and Alzheimer's patients with higher baseline CSF/plasma vitamin C ratios exhibit slower disease progression over the course of one year (Bowman et al., 2009). Other studies found no such associations (Gray et al., 2008; Laurin et al., 2004; Luchsinger et al., 2003; Paraskevas et al., 1997). "
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    ABSTRACT: Vitamin C is a powerful antioxidant and its levels are decreased in Alzheimer's patients. Even sub-clinical vitamin C deficiency could impact disease development. To investigate this principle we crossed APP/PSEN1 transgenic mice with Gulo knockout mice unable to synthesize their own vitamin C. Experimental mice were maintained from 6 weeks of age on standard (0.33 g/L) or reduced (0.099 g/L) levels of vitamin C and then assessed for changes in behavior and neuropathology. APP/PSEN1 mice showed impaired spatial learning in the Barnes maze and water maze that was not further impacted by vitamin C level. However, long-term decreased vitamin C levels led to hyperactivity in transgenic mice, with altered locomotor habituation and increased omission errors in the Barnes maze. Decreased vitamin C also led to increased oxidative stress. Transgenic mice were more susceptible to the activity-enhancing effects of scopolamine and low vitamin C attenuated these effects in both genotypes. These data indicate an interaction between the cholinergic system and vitamin C that could be important given the cholinergic degeneration associated with Alzheimer's disease.
    Pharmacology Biochemistry and Behavior 11/2009; 94(4):543-52. DOI:10.1016/j.pbb.2009.11.009 · 2.78 Impact Factor
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