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: 3.61). 02/2009; 16(1):93-8. DOI: 10.3233/JAD-2009-0923
Source: PubMed

ABSTRACT 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.

Download full-text


Available from: Hiroko Hayama Dodge, Jul 07, 2015
  • Source
    [Show abstract] [Hide abstract]
    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 · 3.00 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    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 · 2.82 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: There is great interest in the nutritional strategies for the prevention of age-related cognitive decline, yet the best methods for nutritional assessment in the populations at risk for dementia are still evolving. Our study objective was to examine the reliability and validity of the 2 common nutritional assessments (plasma nutrient biomarkers and Food Frequency Questionnaire) in the people at risk for dementia. Thirty-eight elders, half with amnestic-mild cognitive impairment were recruited. Nutritional assessments were collected together at the baseline and again at 1 month. Intraclass and Pearson correlation coefficients quantified reliability and validity. Twenty-six nutrients were examined. The reliability was very good or better for 77% (20/26, intraclass correlation coefficients or ICC ≥0.75) of the plasma nutrient biomarkers and for 88% of the food frequency questionnaires (FFQ) estimates. Twelve of the nutrient biomarkers were as reliable as the commonly measured plasma cholesterol (ICC≥0.92). FFQ and plasma long-chain fatty acids (docosahexaenoic acid, r=0.39, eicosapentaenoic acid, r=0.39) and carotenoids (α-carotene, r=0.49; lutein + zeaxanthin, r=0.48; β-carotene, r=0.43; β-cryptoxanthin, r=0.41) were correlated, but these significant correlations were present only in non-impaired elders. The reliability and validity of the FFQ and nutrient biomarkers vary according to the nutrient of interest. Memory deficit attenuates validity and inflates reliability of FFQ reports. Many plasma nutrient biomarkers have very good reliability over 1-month, regardless of memory state. This objective method can circumvent sources of error seen in other less direct and subjective methods of nutritional assessment.
    Alzheimer disease and associated disorders 01/2011; 25(1):49-57. DOI:10.1097/WAD.0b013e3181f333d6 · 2.69 Impact Factor