Under normal conditions, the adult human brain is fueled primarily by
Under normal conditions, the adult human brain is fueled primarily by glucose. for in standard practice, had a diagnosis of probable AD of mild-to-moderate severity (MMSE 14C24), and had received CT for at least 6 months in addition to other approved pharmacotherapy for AD. Response to CT administration as Tipifarnib measured by MMSE scores varied by patient. However, the rate of decline in MMSE scores appeared slower than previously published reports for patients treated with pharmacotherapy alone. Profiling of individual patients may provide insight regarding those most likely to benefit from addition of CT to currently approved AD pharmacotherapy. (= 0.3735, MannCWhitney patients are less responsive to CT than those who are genotype in this study was APOE4+ and showed improvement in her MMSE score after initiation of CT. It has been shown that the e4 allele is a significant risk factor for AD, but that this genotype is uncommon in the general population.15,16 Overall, the annual rate of MMSE decline decreased in four patients and increased in four patients after initiation of CT. The mean (median) annual rates of Tipifarnib decline prior to initiation of CT were ?1.34 (?2.95) and those after addition of CT were ?0.64 (?0.55) for the eight patients included in this report, and the difference between the rates of decline before and after addition of CT to therapy was not significant. Several studies with much larger patient samples have provided information regarding the decline in MMSE scores in patients who were and were not receiving AD-specific therapies. A review of studies published Pparg prior to 2005 indicated a variable rate of decline in MMSE scores of ?0.6 to ?4.4 points per year in patients with AD.17 The REAL.FR (REseau sur la maladie d Alzheimer FRan?ais) cohort has been followed up twice annually with MMSE and Tipifarnib the Alzheimer Disease Assessment Scale-cognitive subscale. A study published in 2011 that included 686 patients from the REAL.FR cohort (90% receiving AD-specific medication) demonstrated an annual decline in MMSE scores of ?2.4 points per year.18 An earlier study of 938 patients with mild-to-moderate AD included in the Italian National Cronos Project, who were receiving donepezil, galantamine, or rivastigmine, indicated an average decline of ?1 point over 36 weeks of follow-up (representing an annual decline of ?1.4 points).19 While several of the cases included in this report suggest that addition of CT to pharmacotherapy may stabilize MMSE scores in patients with mild-to-moderate AD, it should be acknowledged that this measure has important limitations for assessment of cognitive function. The rate of change for MMSE is known to be influenced by several factors including baseline score, age, duration of disease, education, and prior experience with the test;20C22 there were substantial differences in the rates of change for MMSE scores, both before and after addition of CT to therapy, in the eight patients included in this report. The limitations of current pharmacotherapy have prompted interest in diet and dietary supplementation as part of the overall treatment regimen for patients with AD. Meta-analysis of results from six prospective studies published between 2006 and 2009 indicated that high adherence to the Mediterranean diet was associated with a significantly decreased risk for neurodegenerative diseases, including AD,23 but there is no evidence that it slows cognitive decline in patients with AD. Many dietary supplements have been evaluated in AD, and there is both positive and negative evidence for omega-3 fatty acids,24,25 coenzyme Q/idebenone,26,27 and acetyl-L-carnitine.28,29 The CT preparation administered to patients in the cases described is composed of a glycerol backbone with three caprylic fatty acids (C8:0) esterified to the glycerol. Medium chain triglycerides have been used in specialty nutrition for over 40 years. They are commonly employed in patients who have difficulty metabolizing long chain triglycerides, eg, those with pancreatic insufficiency. In addition, medium chain triglycerides have been used in ketogenic diets for children with refractive epilepsy, due.