Diet Intervention and Cerebrospinal Fluid Biomarkers in Amnestic Mild Cognitive Impairment

Geriatric Research, Education, and Clinical Center, Veterans Affairs Puget Sound Health Care System, 1660 S Columbian Way, Seattle, WA 98108, USA.
Archives of neurology (Impact Factor: 7.01). 06/2011; 68(6):743-52. DOI: 10.1001/archneurol.2011.125
Source: PubMed

ABSTRACT To compare the effects of a 4-week high-saturated fat/high-glycemic index (HIGH) diet with a low-saturated fat/low-glycemic index (LOW) diet on insulin and lipid metabolism, cerebrospinal fluid (CSF) markers of Alzheimer disease, and cognition for healthy adults and adults with amnestic mild cognitive impairment (aMCI).
Randomized controlled trial.
Veterans Affairs Medical Center clinical research unit.
Forty-nine older adults (20 healthy adults with a mean [SD] age of 69.3 [7.4] years and 29 adults with aMCI with a mean [SD] age of 67.6 [6.8] years).
Participants received the HIGH diet (fat, 45% [saturated fat, > 25%]; carbohydrates, 35%-40% [glycemic index, > 70]; and protein, 15%-20%) or the LOW diet (fat, 25%; [saturated fat, < 7%]; carbohydrates, 55%-60% [glycemic index, < 55]; and protein, 15%-20%) for 4 weeks. Cognitive tests, an oral glucose tolerance test, and lumbar puncture were conducted at baseline and during the fourth week of the diet.
The CSF concentrations of β-amyloid (Aβ42 and Aβ40), tau protein, insulin, F2-isoprostanes, and apolipoprotein E, plasma lipids and insulin, and measures of cognition.
For the aMCI group, the LOW diet increased CSF Aβ42 concentrations, contrary to the pathologic pattern of lowered CSF Aβ42 typically observed in Alzheimer disease. The LOW diet had the opposite effect for healthy adults, ie, decreasing CSF Aβ42, whereas the HIGH diet increased CSF Aβ42. The CSF apolipoprotein E concentration was increased by the LOW diet and decreased by the HIGH diet for both groups. For the aMCI group, the CSF insulin concentration increased with the LOW diet, but the HIGH diet lowered the CSF insulin concentration for healthy adults. The HIGH diet increased and the LOW diet decreased plasma lipids, insulin, and CSF F2-isoprostane concentrations. Delayed visual memory improved for both groups after completion of 4 weeks of the LOW diet.
Our results suggest that diet may be a powerful environmental factor that modulates Alzheimer disease risk through its effects on central nervous system concentrations of Aβ42, lipoproteins, oxidative stress, and insulin.


Available from: Nadia Postupna, Jun 08, 2015
  • [Show abstract] [Hide abstract]
    ABSTRACT: Epidemiological evidence linking diet, one of the most important modifiable lifestyle factors, and risk of Alzheimer's disease (AD) is rapidly increasing. However, there is little or no evidence for a direct association between dietary nutrients and brain biomarkers of AD. This study identifies nutrient patterns associated with major brain AD biomarkers in a cohort of clinically and cognitively normal (NL) individuals at risk for AD. Cross-sectional study. Manhattan (broader area). Fifty-two NL individuals (age 54+12 y, 70% women, Clinical Dementia Rating=0, MMSE>27, neuropsychological test performance within norms by age and education) with complete dietary information and cross-sectional, 3D T1-weighted Magnetic Resonance Imaging (MRI; gray matter volumes, GMV, a marker of brain atrophy), 11C-Pittsburgh compound-B (PiB; a marker of fibrillar amyloid-β, Aβ) and 18F-fluorodeoxyglucose (FDG; a marker of glucose metabolism, METglc) Positron Emission Tomography (PET) scans were examined. Dietary intake of 35 nutrients associated with cognitive function and AD was assessed using the Harvard/Willet Food Frequency Questionnaire. Principal component analysis was used to generate nutrient patterns (NP) from the full nutrient panel. Statistical parametric mapping and voxel based morphometry were used to assess the associations of the identified NPs with AD biomarkers. None of the participants were diabetics, smokers, or met criteria for obesity. Five NPs were identified: NP1 was characterized by most B-vitamins and several minerals [VitB and Minerals]; NP2 by monounsaturated and polyunsaturated fats, including ω-3 and ω-6 PUFA, and vitamin E [VitE and PUFA]; NP3 by vitamin A, vitamin C, carotenoids and dietary fibers [Anti-oxidants and Fibers]; NP4 by vitamin B12, vitamin D and zinc [VitB12 and D]; NP5 by saturated, trans-saturated fats, cholesterol and sodium [Fats]. Voxel-based analysis showed that NP4 scores [VitB12 and D] were positively associated with METglc and GMV, and negatively associated with PiB retention in AD-vulnerable regions (p<0.001). In addition, both METglc and GMV were positively associated with NP2 scores [VitE and PUFA], and negatively associated with NP5 scores [Fats] (p<0.001), and METglc was positively associated with higher NP3 scores [Anti-oxidants and Fibers] (p<0.001). Adjusting for age, gender, ethnicity, education, caloric intake, BMI, alcohol consumption, family history and Apolipoprotein E (APOE) status did not attenuate these relationships. The identified 'AD-protective' nutrient combination was associated with higher intake of fresh fruit and vegetables, whole grains, fish and low-fat dairies, and lower intake of sweets, fried potatoes, high-fat dairies, processed meat and butter. Specific dietary NPs are associated with brain biomarkers of AD in NL individuals, suggesting that dietary interventions may play a role in the prevention of AD by modulating AD-risk through its effects on Aβ and associated neuronal impairment.
    The Journal of Nutrition Health and Aging 01/2015; 19(4):413-23. DOI:10.1007/s12603-014-0534-0 · 2.66 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To investigate the interrelationships among blood nutrient biomarkers, the Framingham Stroke Risk Profile (FSRP), and cognitive impairment features in mild cognitive impairment (MCI) subjects and to verify whether nutrient biomarkers and FSRP are risk factors for MCI. According to the criteria for MCI developed by Petersen, 81 subjects aged 50-80 years were divided into a normal control group (NC group, n = 36) and an MCI group (n = 45). Then, the MCI group was divided into an amnestic MCI (a-MCI) and a multidomain MCI (md-MCI) group. All subjects were administered a comprehensive health history to calculate their FSRP score and a thorough neuropsychological assessment of four cognitive domains. Blood samples from all subjects were collected to measure the nutrient biomarkers. FSRP score was not only associated with memory function, but also with executive function, which itself had a negative relationship with eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and total n-3 polyunsaturated fatty acids (n-3PUFAs) levels, and a positive relationship with the ratio of n-6 PUFAs to n-3 PUFAs(n6/n3). Compared with the NC group, the concentrations of EPA, DHA, 25-hydroxy vitamin D (25OHD), and folate and the ratio of n3/n6 in the md-MCI group were significantly lower. In the a-MCI group, only DHA concentrations and the ratio of n3/n6 were significantly lower. After adjustment for potential confounding variables, low education level [Adjusted OR=8.71 (95%CI: 1.83-41.50), p trend = 0.007], decreased plasma 25OHD [Adjusted OR = 4.41 (95% CI: 1.08-17.94), p trend=0.04] and decreased plasma DHA [Adjusted OR = 6.69 (95% CI: 1.37-32.72), p = 0.02] were associated with a higher risk of MCI. Several nutrient biomarkers in MCI patients, especially in md-MCI patients, were lower compared with healthy controls, suggesting that lower 25OHD and DHA levels are risk factors for MCI. However, we found no evidence that FSRP is an early biomarker of MCI.
    The Journal of Nutrition Health and Aging 01/2015; 19(1):39-47. DOI:10.1007/s12603-014-0510-8 · 2.66 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Demonstration of brain accumulation of fibrillar amyloid beta protein via positron emission tomography (PET) with amyloid specific ligands may support the diagnosis of Alzheimer's disease (AD). There is increasing recognition of the potential use of amyloid imaging to detect in vivo the pathology of AD in individuals with no ostensible cognitive impairment. Research use of amyloid PET in cognitively normal patients will be key to pursuit of therapies able to delay cognitive impairment and dementia due to AD. We review the pros and cons of disclosing amyloid imaging results to cognitively normal individuals in clinical and research settings and provide draft recommendations.
    02/2013; 3(1):43-51. DOI:10.2217/nmt.12.75