Declining brain glucose metabolism in normal individuals with a maternal history of Alzheimer disease

Mosconi, Lisa; Mistur, Rachel L.; Switalski, Remigiusz; Bryś, Mirosław; Glodzik, Lidia; Rich, Kenneth; Pirraglia, Elizabeth; Tsui, Wai; Santi, Susan De; Leon, Mony J. de

doi:10.1212/01.wnl.0000333247.51383.43

Cited by 181 publications

(185 citation statements)

References 35 publications

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“…Over a two-year follow-up, CMRglc impairment in maternal AD individuals was found to be progressive [69], with longitudinal CMRglc reductions in the posterior cingulate/precuneus, parietotemporal and frontal cortices. In contrast, individuals with an AD-affected father and those with no family history of AD showed longitudinal CMRglc reductions only in the frontal cortex, which is a typical effect of aging.…”

Section: Fdg Pet and Apoe-associated Genetic Riskmentioning

confidence: 96%

FDG PET and the genetics of dementia

Nacmias

Berti

Piaceri

et al. 2013

Clin Transl Imaging

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Dementias are the most common neurodegenerative diseases and they are increasingly becoming a major public health problem. The most common form of dementia, affecting over 20 million people worldwide, is Alzheimer's disease (AD). AD is a neurodegenerative disease of the central nervous system mainly found in older adults, with an incidence that increases with age. With the development of newer technologies, including genetic screening technologies and PET/MRI scanning, the role of genetic studies and neuroimaging is being redefined; indeed, these approaches are able to provide support not only in the clinical diagnosis of dementia, but also in its presymptomatic evaluation. Many researchers agree that early identification of AD, before abnormal accumulation of amyloid and tau proteins, could provide an opportunity to hinder the progression of the disease. [18 F]2-fluoro-2-deoxy-D-glucose (FDG) PET studies have shown that decreased glucose metabolism in AD precedes clinical diagnosis and that the degree of clinical disability in AD correlates closely with the magnitude of the reduction in brain glucose metabolism. Data on presymptomatic mutation carriers from families with known early-onset autosomal dominant AD (familial AD) show reductions in the cerebral metabolic rate of glucose (CMRglc), consistent with the expected AD PET pattern, in the absence of severe atrophy on MRI. These results suggest that PET CMRglc measures have the potential to serve as preclinical biomarkers of dementia, useful also for tracking disease progression. This review highlights the role of genetics and FDG PET in understanding the pathogenesis of dementia.

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Section: Fdg Pet and Apoe-associated Genetic Riskmentioning

confidence: 96%

FDG PET and the genetics of dementia

Nacmias

Berti

Piaceri

et al. 2013

Clin Transl Imaging

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show abstract

“…Cellular bioenergetics at the level of the mitochondrion is intimately linked to glucose metabolism through the provision of pyruvate as a substrate for respiration and NADPH for protection against oxidative stress. Importantly, glucose metabolism is altered in stroke and neurodegenerative diseases, [33][34][35][36][37] emphasizing the need for understanding the potential link between cellular bioenergetics, autophagy and neuronal viability. In support of this concept, our published studies in differentiated SH-SY5Y neuroblastoma cells have shown that HNE decreases mitochondrial function and glycolysis, and can cause cell death.…”

Section: Basic Research Papermentioning

confidence: 99%

Inhibition of glycolysis attenuates 4-hydroxynonenal-dependent autophagy and exacerbates apoptosis in differentiated SH-SY5Y neuroblastoma cells

et al. 2013

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“…In the present article, we extend these prior findings by investigating the longitudinal effect of FH and APOE4 on brain morphometry within this cohort, with a particular focus on temporoparietal regions that are now known to be vulnerable to AD pathology. 16,17 In addition, because it has recently been shown that the sex of the ADaffected parent may be influential, with maternal FH being more deleterious, 5,7,8,18 we conducted supplementary analyses to determine whether any observed FH effects were possibly driven by maternal FH. In parallel analyses, we also investigated the effect of FH and APOE4 on cognitive decline.…”

mentioning

confidence: 99%

Family history of Alzheimer disease predicts hippocampal atrophy in healthy middle-aged adults

Okonkwo¹,

Xu²,

Dowling³

et al. 2012

Neurology

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Objective: To evaluate the longitudinal influence of family history (FH) of Alzheimer disease (AD) and apolipoprotein E ⑀4 allele (APOE4) on brain atrophy and cognitive decline over 4 years among asymptomatic middle-aged individuals.Methods: Participants were cognitively healthy adults with (FHϩ) (n ϭ 60) and without (FHϪ) (n ϭ 48) a FH of AD (mean age at baseline 54 years) enrolled in the Wisconsin Registry for Alzheimer's Prevention. They underwent APOE genotyping, cognitive testing, and an MRI scan at baseline and 4 years later. A covariate-adjusted voxel-based analysis interrogated gray matter (GM) modulated probability maps at the 4-year follow-up visit as a function of FH and APOE4. We also examined the influence of parent of origin on GM atrophy. Parallel analyses investigated the effects of FH and APOE4 on cognitive decline.Results: Neither FH nor APOE4 had an effect on regional GM or cognition at baseline. Longitudinally, a FH ϫ APOE4 interaction was found in the right posterior hippocampus, which was driven by a significant difference between the FHϩ and FHϪ subjects who were APOE4Ϫ. In addition, a significant FH main effect was observed in the left posterior hippocampus. No significant APOE4 main effects were detected. Persons with a maternal history of AD were just as likely as those with a paternal history of AD to experience posterior hippocampal atrophy. There was no longitudinal decline in cognition within the cohort. Conclusion:Over a 4-year interval, asymptomatic middle-aged adults with FH of AD exhibit significant atrophy in the posterior hippocampi in the absence of measurable cognitive changes. This result provides further evidence that detectable disease-related neuroanatomic changes do occur early in the AD pathologic cascade. Neurology ® 2012;78:1769-1776 GLOSSARY AD ϭ Alzheimer disease; ANCOVA ϭ analysis of covariance; FH ϭ family history; GM ϭ gray matter; mFH ϭ maternal family history; MNI ϭ Montreal Neurological Institute; pFH ϭ paternal family history; WRAP ϭ Wisconsin Registry for Alzheimer's Prevention.

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Declining brain glucose metabolism in normal individuals with a maternal history of Alzheimer disease

Abstract: Background:At cross-section, cognitively normal individuals (NL) with a maternal history of late-

Cited by 181 publications

References 35 publications

FDG PET and the genetics of dementia

FDG PET and the genetics of dementia

Inhibition of glycolysis attenuates 4-hydroxynonenal-dependent autophagy and exacerbates apoptosis in differentiated SH-SY5Y neuroblastoma cells

Family history of Alzheimer disease predicts hippocampal atrophy in healthy middle-aged adults

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