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      Neuropsychiatric Disease and Treatment (submit here)

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      Retrospective cohort study of the efficacy of caprylic triglyceride in patients with mild-to-moderate alzheimer’s disease

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          Abstract

          Background

          The purpose of this study was to evaluate the effects of caprylic triglyceride (CT) in patients with mild-to-moderate Alzheimer’s disease (AD) in routine clinical practice via review of medical records and caregiver questionnaires.

          Methods

          Participants were outpatients aged ≥50 years with a diagnosis of probable mild-to-moderate AD who had received CT for ≥6 months. The primary outcome was change from baseline in the patient’s condition as rated by the treating physician using a physician’s overall assessment.

          Results

          A total of 55 patients were included. The physician’s overall assessment indicated that ~80% of patients who had CT added to ongoing pharmacotherapy were stable or improved. Mini-Mental State Examination scores also remained stable over 15 months of therapy (20.6 ± 3.0 at baseline and 20.1 ± 5.6 at follow-up, P = 0.5233, n = 27). Caregiver assessments indicated that most patients were stable or improved with respect to memory and ability to carry out activities of daily living. The most frequent adverse events with CT involved the gastrointestinal system.

          Conclusion

          Results from this chart review indicate that addition of CT to pharmacotherapy was associated with stable disease or improvement over a follow-up period of 18.8 months.

          Most cited references34

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          Functional brain abnormalities in young adults at genetic risk for late-onset Alzheimer's dementia.

          Fluorodeoxyglucose positron emission tomography (PET) studies have found that patients with Alzheimer's dementia (AD) have abnormally low rates of cerebral glucose metabolism in posterior cingulate, parietal, temporal, and prefrontal cortex. We previously found that cognitively normal, late-middle-aged carriers of the apolipoprotein E epsilon4 allele, a common susceptibility gene for late-onset Alzheimer's dementia, have abnormally low rates of glucose metabolism in the same brain regions as patients with probable AD. We now consider whether epsilon4 carriers have these regional brain abnormalities as relatively young adults. Apolipoprotein E genotypes were established in normal volunteers 20-39 years of age. Clinical ratings, neuropsychological tests, magnetic resonance imaging, and PET were performed in 12 epsilon4 heterozygotes, all with the epsilon3/epsilon4 genotype, and 15 noncarriers of the epsilon4 allele, 12 of whom were individually matched for sex, age, and educational level. An automated algorithm was used to generate an aggregate surface-projection map that compared regional PET measurements in the two groups. The young adult epsilon4 carriers and noncarriers did not differ significantly in their sex, age, educational level, clinical ratings, or neuropsychological test scores. Like previously studied patients with probable AD and late-middle-aged epsilon4 carriers, the young epsilon4 carriers had abnormally low rates of glucose metabolism bilaterally in the posterior cingulate, parietal, temporal, and prefrontal cortex. Carriers of a common Alzheimer's susceptibility gene have functional brain abnormalities in young adulthood, several decades before the possible onset of dementia.
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            Effectiveness of cholinesterase inhibitors and memantine for treating dementia: evidence review for a clinical practice guideline.

            The effectiveness of the 5 U.S. Food and Drug Administration-approved pharmacologic therapies for dementias in achieving clinically relevant improvements is unclear. To review the evidence for the effectiveness of cholinesterase inhibitors (donepezil, galantamine, rivastigmine, and tacrine) and the neuropeptide-modifying agent memantine in achieving clinically relevant improvements, primarily in cognition, global function, behavior, and quality of life, for patients with dementia. Cochrane Central Register of Controlled Trials, MEDLINE, PREMEDLINE, EMBASE, Allied and Complementary Medicine Database, CINAHL, AgeLine, and PsycINFO from January 1986 through November 2006. English-language randomized, controlled trials were included in the review if they evaluated pharmacologic agents for adults with a diagnosis of dementia, did not use a crossover design, and had a quality score of at least 3 on the Jadad scale. Data were extracted on study characteristics and outcomes, including adverse events. Effect sizes were calculated and data were combined when appropriate. 96 publications representing 59 unique studies were eligible for this review. Both cholinesterase inhibitors and memantine had consistent effects in the domains of cognition and global assessment, but summary estimates showed small effect sizes. Outcomes in the domains of behavior and quality of life were evaluated less frequently and showed less consistent effects. Most studies were of short duration (6 months), which limited their ability to detect delay in onset or progression of dementia. Three studies directly compared different cholinesterase inhibitors and found no differences in cognition and behavior. Limitations of available studies included short duration, inclusion of only patients with mild to moderate Alzheimer disease, poor reporting of adverse events, lack of clear definitions for statistical significance, limited evaluation of behavior and quality-of-life outcomes, and limited direct comparison of different treatments. Treatment of dementia with cholinesterase inhibitors and memantine can result in statistically significant but clinically marginal improvement in measures of cognition and global assessment of dementia.
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              D-beta-hydroxybutyrate protects neurons in models of Alzheimer's and Parkinson's disease.

              The heroin analogue 1-methyl-4-phenylpyridinium, MPP(+), both in vitro and in vivo, produces death of dopaminergic substantia nigral cells by inhibiting the mitochondrial NADH dehydrogenase multienzyme complex, producing a syndrome indistinguishable from Parkinson's disease. Similarly, a fragment of amyloid protein, Abeta(1-42), is lethal to hippocampal cells, producing recent memory deficits characteristic of Alzheimer's disease. Here we show that addition of 4 mM d-beta-hydroxybutyrate protected cultured mesencephalic neurons from MPP(+) toxicity and hippocampal neurons from Abeta(1-42) toxicity. Our previous work in heart showed that ketone bodies, normal metabolites, can correct defects in mitochondrial energy generation. The ability of ketone bodies to protect neurons in culture suggests that defects in mitochondrial energy generation contribute to the pathophysiology of both brain diseases. These findings further suggest that ketone bodies may play a therapeutic role in these most common forms of human neurodegeneration.
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                Author and article information

                Journal
                Neuropsychiatr Dis Treat
                Neuropsychiatr Dis Treat
                Neuropsychiatric Disease and Treatment
                Neuropsychiatric Disease and Treatment
                Dove Medical Press
                1176-6328
                1178-2021
                2013
                2013
                23 October 2013
                : 9
                : 1619-1627
                Affiliations
                [1 ]Union Associated Physicians Clinic, Terre Haute, IN, USA
                [2 ]Indiana University School of Medicine, Terre Haute, IN, USA
                [3 ]Mt Sinai Medical Center of Miami, Aventura Hospital, Aventura, FL, USA
                Author notes
                Correspondence: Steven Douglas Maynard, Union Associated Physicians Clinic, Indiana University School of Medicine, 1739 N 4th Street, Terre Haute, IN 47804, USA, Tel +1 812 242 3125, Fax +1 812 242 3446, Email stevendmay2002@ 123456yahoo.com
                Article
                ndt-9-1619
                10.2147/NDT.S52331
                3810439
                3f041ecc-5cf3-4ae9-8ec9-859a40e9c3d0
                © 2013 Maynard and Gelblum. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License

                The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                History
                Categories
                Original Research

                Neurology
                ketosis,cognition,alzheimer’s disease,metabolism,caprylic triglyceride
                Neurology
                ketosis, cognition, alzheimer’s disease, metabolism, caprylic triglyceride

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