Positron emission tomographic studies of aging and Alzheimer disease. AJNR Am J Neuroradiol 4:568-571
In this study the positron emission tomographic (PET)-18F-2-deoxy-2-fluoro-D-glucose (FDG) technique was used to study both normal aging and senile dementia. The results derived from 15 young normal subjects (mean age, 26 +/- 5 years) and 22 elderly normal subjects (mean age, 66 +/- 7 years) failed to indicate significant metabolic changes associated with age. A group of 24 patients with senile dementia (mean age, 73 +/- 7 years) showed consistent diminutions in regional glucose use relative to the elderly normals. Across all brain regions the diminutions were 17%-24%. There were also significant correlations between the measures of glucose use and the measures of cognitive functioning. Discriminant function classification analysis results indicate that better than 80% classification accuracy can be achieved for individual PET measures. These data suggest a possible future diagnostic use of PET in senile dementia.
Available from: PubMed Central
- "18-Fluorodeoxyglucose (18F) positron emission tomography (FDG PET) studies in the early 1980s compared AD subjects with normal controls and found significant diminished cerebral glucose metabolism (DCGM) in AD patients. In these studies, significant correlations were found between DCGM and worsening performance on measures of cognitive function (de Leon et al., 1983). Subsequent studies have revealed that DCGM in AD is not simply a global decrease in glucose use across the brain, but rather maps to specific regions found in the posterior cingulate and parietal, temporal, and prefrontal cortices. "
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ABSTRACT: Objective: To examine the effect of 109 days of caprylic triglyceride (CT) in a 70-year-old male with mild Alzheimer’s disease (AD).
Background: Cerebral metabolism is limited to glucose under most conditions, and diminished cerebral glucose metabolism is a characteristic feature of AD. Another substrate available for cerebral metabolism is ketone bodies. Ketone bodies (KB) are normally derived from fat stores under conditions of low glucose availability as an alternative energy substrate to glucose. KB can also be produced by oral administration of CT. Prior studies suggest that the alternative energy source of CT may improve cognitive function due to mild to moderate AD, by circumventing the diminished glucose metabolism.
Method: The effect of CT was analyzed in a single-case of mild AD with cognitive alterations in an open label study. Study outcomes included the Montreal cognitive assessment (MoCA), mini mental state exam (MMSE), and 18-fluorodeoxyglucose (18F) positron emission tomography (FDG PET) scans.
Results: After 109 days of CT, MoCA scores changed from a baseline value of 24–28, and MMSE scores changed from 23 to 28. No changes were observed on FDG PET scans.
Conclusion: The results suggest that, in a case of mild AD, CT may have affected cognitive function, assessed by means of MMSE and MoCA, although glucose uptake and metabolism remained unchanged.
Frontiers in Aging Neuroscience 07/2014; 6:133. DOI:10.3389/fnagi.2014.00133 · 4.00 Impact Factor
Available from: Hilkka Soininen
- "Since stress conditions related to iNPH and AD, such as ischemia and hypoxia, appear to be equally important for the increase in both β- and γ-secretase activities, it is somewhat puzzling that similar effects on the activity of these secretases cannot be observed in both iNPH and AD brain. Yet the disturbances in the brain metabolism might be less dramatic in iNPH than in AD, where impaired glucose metabolism is also considered as a common hallmark in addition to hypoxia and ischemia –, . "
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ABSTRACT: The potential similarity between the brain pathology of idiopathic normal pressure hydrocephalus (iNPH) and Alzheimer disease (AD) is intriguing and thus further studies focusing on the underlying molecular mechanisms may offer valuable information for differential diagnostics and the development of treatments for iNPH. Here, we investigated β- and γ-secretase activities in relation to amyloid-β (Aβ) pathology in the brain tissue samples collected from iNPH and AD patients. β- and γ-secretase activities were measured from the frontal cortical biopsies of 26 patients with suspected iNPH as well as post-mortem tissue samples from the inferior temporal cortex of 74 AD patients and eight subjects without neurofibrillary pathology. In iNPH samples with detectable Aβ plaques, γ-secretase activity was significantly increased (∼1.6-fold) when compared to iNPH samples without Aβ plaques (p = 0.009). In the AD samples, statistically significant differences in the γ-secretase activity were not observed with respect to disease severity (mild, moderate and severe AD according to neurofibrillary pathology). Conversely, β-secretase activity was unaltered in iNPH samples with or without Aβ plaques, while it was significantly increased in relation to disease severity in the AD patients. These results show for the first time increased γ-secretase but not β-secretase activity in the biopsy samples from the frontal cortex of iNPH patients with AD-like Aβ pathology. Conversely, the opposite was observed in these secretase activities in AD patients with respect to neurofibrillary pathology. Despite the resemblances in the Aβ pathology, iNPH and AD patients appear to have marked differences in the cellular mechanisms responsible for the production of Aβ.
PLoS ONE 07/2014; 9(4):e93717. DOI:10.1371/journal.pone.0093717 · 3.23 Impact Factor
Available from: Samuel T Henderson
- "Alzheimer's disease is characterized by an early and progressive decrease in the cerebral metabolic rate of glucose (CMRglc) [3-5]. The primary regions affected in AD are the posterior cingulate and the parietal, temporal, and prefrontal cortices. "
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ABSTRACT: To examine the effect of genetic variation in APOE, IDE and IL1B on the response to induced ketosis in the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) in subjects with mild to moderate Alzheimer's disease (AD).
Genotype effects on ADAS-Cog scores from a randomized, double-blind, placebo-controlled study in mild to moderate AD were examined by an overall two way analysis of variance. In addition, interactions with the carriage status of the epsilon 4 allele of the APOE gene (APOE4) were examined.
Significant differences in response to induced ketosis were found among non-carriers of putative gain-of-function polymorphisms in rs1143627 and rs16944 in the IL1B gene and among variants of the polymorphism rs2251101 in the IDE gene. Significant differences were found among non-carriers of the APOE4 gene, with notable improvement among the E3/E3 genotype group.
Variants in APOE, IL1B and IDE may influence the cognitive response to induced ketosis in patients with mild to moderate AD.
This trial was registered with ClinicalTrials.gov, registry number NCT00142805.
BMC Medical Genetics 10/2011; 12(1):137. DOI:10.1186/1471-2350-12-137 · 2.08 Impact Factor
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