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: 7.42). 06/2011; 68(6):743-52. DOI: 10.1001/archneurol.2011.125
Source: PubMed


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.

Download full-text


Available from: Nadia Postupna, Oct 13, 2015
35 Reads
  • Source
    • "Similarly, when subjects with mild cognitive impairment were maintained for 1 month on a low glycemic diet, they exhibited improved delayed visual memory, cerebrospinal fluid biomarkers of Ab metabolism and brain bioenergetics (Bayer-Carter et al., 2011). Studies in which cognitive function, regional brain volumes, neural network activity, and biochemical analyses of cerebrospinal fluid are measured in human subjects before and during an extended period of IF should clarify the impact of IF on human brain structure and function. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Fasting has been practiced for millennia, but, only recently, studies have shed light on its role in adaptive cellular responses that reduce oxidative damage and inflammation, optimize energy metabolism, and bolster cellular protection. In lower eukaryotes, chronic fasting extends longevity, in part, by reprogramming metabolic and stress resistance pathways. In rodents intermittent or periodic fasting protects against diabetes, cancers, heart disease, and neurodegeneration, while in humans it helps reduce obesity, hypertension, asthma, and rheumatoid arthritis. Thus, fasting has the potential to delay aging and help prevent and treat diseases while minimizing the side effects caused by chronic dietary interventions.
    Cell metabolism 01/2014; 19(2). DOI:10.1016/j.cmet.2013.12.008 · 17.57 Impact Factor
  • Source
    • "Abbreviations: AHI4%, apnea and/or hypopnea with 4% O 2 -desaturation index; ApoE, apolipoprotein E4; CSF, cerebrospinal fluid; p-tau, phosphorylated-tau. findings, some authors have described a model in which brain CSF Ab-42 concentrations rise with age in presymptomatic disease, to a " tipping point " at the onset of fibrillar Ab deposition, followed by CSF Ab-42 decreases (Bayer-Carter et al., 2011). In this model, recently verified in familial AD mutation carriers (Reiman et al., 2012), any condition that increases levels of Ab-42 in the early presymptomatic stages of the disease would increase the risk for developing LOAD, and our findings could be interpreted as early Ab-42 increases secondary to intermittent hypoxia before the consequential decreases in Ab-42 that follow amyloid plaque formation. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Previous studies have suggested a link between sleep disordered breathing (SDB) and dementia risk. In the present study, we analyzed the relationship between SDB severity, cerebrospinal fluid (CSF) Alzheimer's disease-biomarkers, and the ApoE alleles. A total of 95 cognitively normal elderly participants were analyzed for SDB severity, CSF measures of phosphorylated-tau (p-tau), total-tau (t-tau), and amyloid beta 42 (Aβ-42), as well as ApoE allele status. In ApoE3+ subjects, significant differences were found between sleep groups for p-tau (F[df2] = 4.3, p = 0.017), and t-tau (F[df2] = 3.3, p = 0.043). Additionally, among ApoE3+ subjects, the apnea and/or hypopnea with 4% O2-desaturation index was positively correlated with p-tau (r = 0.30, p = 0.023), t-tau (r = 0.31, p = 0.021), and Aβ-42 (r = 0.31, p = 0.021). In ApoE2+ subjects, the apnea and/or hypopnea with 4% O2-desaturation index was correlated with lower levels of CSF Aβ-42 (r = -0.71, p = 0.004), similarly to ApoE4+ subjects where there was also a trend toward lower CSF Aβ-42 levels. Our observations suggest that there is an association between SDB and CSF Alzheimer's disease-biomarkers in cognitively normal elderly individuals. Existing therapies for SDB such as continuous positive airway pressure could delay the onset to mild cognitive impairment or dementia in normal elderly individuals.
    Neurobiology of aging 12/2013; 35(6). DOI:10.1016/j.neurobiolaging.2013.12.030 · 5.01 Impact Factor
  • Source
    • "We recently conducted a controlled intervention aimed at examining the effects of diet on cognitive function and CSF biomarkers in older adults with and without cognitive impairment [29]. Participants consumed a high-saturated fat, high glycemic index (HIGH) diet (a pattern associated with T2D and insulin resistance), or a low-saturated fat, low glycemic index (LOW) diet for four weeks. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The recognition of Alzheimer's disease (AD) as a heterogeneous disorder that results from incremental pathological changes in dynamic organismic systems is essential to move beyond the unidimensional approaches to prevention and therapy that have proven largely ineffective to date. Biological systems related to insulin metabolism are arguably the most critical regulators of longevity and corporeal aging. Our work has focused on identifying the relationship of the insulin network to brain aging, and determining the mechanisms through which insulin dysregulation promotes AD pathological processes. Candidate mechanisms include the effects of insulin on amyloid-β, cerebral glucose metabolism, vascular function, lipid metabolism, and inflammation/oxidative stress. It is likely that different nodes of the insulin network are perturbed for subgroups of AD patients, or that for some subgroups, pathways independent of insulin are critical pathogenetic factors. New methods from systems network analyses may help to identify these subgroups, which will be critical for devising tailored prevention and treatment strategies. In the following review, we will provide a brief description of the role of insulin in normal brain function, and then focus more closely on recent evidence regarding the mechanisms through which disruption of that role may promote AD pathological processes. Finally, we will discuss the implications of this area for AD therapeutics and prevention.
    Journal of Alzheimer's disease: JAD 08/2012; 33(Suppl 1). DOI:10.3233/JAD-2012-129042 · 4.15 Impact Factor
Show more