Cerebral glucose metabolism in patients with AD and different
            <i>APOE</i>
            genotypes

Drzezga, Alexander; Riemenschneider, Matthias; Strassner, B.; Grimmer, Timo; Peller, M.; Knoll, Abraham; Wagenpfeil, Stefan; Minoshima, Satoshi; Schwaiger, Markus; Kurz, Alexander

doi:10.1212/01.wnl.0000148478.39691.d3

Cited by 109 publications

(84 citation statements)

References 38 publications

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“…FDG-PET studies of presymptomatic individuals carrying autosomal dominant mutations responsible for early-onset familial AD also show consistent hypometabolism in these regions, as long as 15 years before symptoms onset (7,8). Studies in MCI, considered by many as a transitional state between healthy aging and dementia (13), have shown severe hypometabolism in these same brain regions among MCI patients before converting to AD as compared with those who remained stable over time (9)(10)(11)20). We recently showed that reduced MTL CMRglc in normal elderly is a risk factor for declining to MCI and AD (15,16).…”

Section: Discussionmentioning

confidence: 91%

Maternal family history of Alzheimer's disease predisposes to reduced brain glucose metabolism

Mosconi

Bryś

Switalski

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

215

232

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Having a parent affected with late-onset Alzheimer's disease (AD) is a risk factor for developing AD among cognitively normal subjects. We examined whether cognitively normal subjects with a parental family history of AD show cerebral metabolic rate of glucose (CMRglc) reductions consistent with AD as compared with those without a family history and whether there are parent gender effects. Fortynine 50-to 80-year-old normal subjects were examined who received clinical, neuropsychological, and 2-[ 18 F]fluoro-2-deoxy-D-glucosepositron emission tomography examinations, including 16 subjects with a maternal (FHm) and eight with a paternal (FHp) family history of AD and 25 with no family history (FH ؊ ). FH groups were comparable for demographic and neuropsychological measures. As compared with both FH ؊ and FHp groups, FHm subjects showed CMRglc reductions in the same regions as clinically affected AD patients, involving the posterior cingulate cortex/precuneus, parietotemporal and frontal cortices, and medial temporal lobes (P < 0.05, corrected for multiple comparisons). These effects remained significant after accounting for possible risk factors for AD, including age, gender, education, apolipoprotein E genotype, and subjective memory complaints. No CMRglc differences were found between FHp and FH ؊ subjects. This study shows a relationship between reduced CMRglc in AD-vulnerable brain regions and a maternal family history of AD in cognitively normal individuals.A fter advanced age, the most significant risk factor for late-onset Alzheimer's disease (AD) is a family history of AD (1). Normal individuals with a first-degree relative affected by AD, especially a parent, are at a 4-to 10-fold higher risk for developing AD as compared with individuals with a negative family history (2-4). Apart from the rare early-onset form of familial AD related to autosomal dominant genetic mutations, genes with a clear Mendelian pattern of transmission for lateonset familial AD have not been identified. To date, the 4 allele of the apolipoprotein E (ApoE) gene is the only established genetic risk factor for late-onset AD and is found in Ϸ40% of late-onset AD cases with a positive family history (1). The ApoE-4 genotype has, however, no clear familial pattern of transmission and appears to act as a risk modifier by lowering the age at onset of clinical symptoms, rather than as a genetic determinant (see ref. 5 for review), indicating that other factors contribute to the etiology and phenotypic expression of disease. The biological mechanisms through which family history of AD confers increased susceptibility to late-onset AD are not known.A consistent feature of AD is the marked reduction of the cerebral metabolic rate of glucose (CMRglc) as measured by using positron emission tomography (PET) imaging with 2-[ 18 F]fluoro-2-deoxy-D-glucose (FDG) as the tracer (FDG-PET). FDG-PET studies demonstrate a specific pattern of CMRglc impairment in AD, involving the parietotemporal, posterior cingulate, and to a lesser extent frontal cort...

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Section: Discussionmentioning

confidence: 91%

Maternal family history of Alzheimer's disease predisposes to reduced brain glucose metabolism

Mosconi

Bryś

Switalski

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

215

232

View full text Add to dashboard Cite

show abstract

“…Carriers of the APOE*4 allele (APOE*4+) have an increased risk of developing mild cognitive impairment (MCI) and AD (11,50,66) and appear to have increased pathologic burden (54,67). Imaging with PET and SPECT lend support to the hypothesis that the APOE*4 allele worsens AD, with both increased (29,39) and decreased (17,35,39,51) resting metabolism being reported in demented APOE*4 carriers as compared to demented non-carriers. In MCI, carriers of the APOE*4 allele reduced metabolism in the parietal-temporal regions and medial parietal lobe, including the posterior cingulate and retrosplenial area (40), perhaps reflecting greater pathologic burden and worse prognosis for these patients (for review see (10,41)).…”

Section: Introductionmentioning

confidence: 90%

Altered medial temporal lobe responses during visuospatial encoding in healthy APOE*4 carriers

Borghesani¹,

Johnson²,

Shelton³

et al. 2008

Neurobiology of Aging

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The apolipoprotein ε4 allele (APOE*4) is a major genetic risk factor for Alzheimer's disease (AD) and has been associated with altered cortical activation as assessed by functional neuroimaging in cognitively normal younger and older carriers. We chose to evaluate medial temporal lobe (MTL) activation during encoding and recognition using a perspective dependent (route or survey) visuospatial memory task by monitoring the blood-oxygen-level-dependent (BOLD) fMRI response in older, non-demented APOE*4 carriers (APOE*4+) and non-carriers (APOE*4−). During encoding, the APOE*4− group had greater average task-associated BOLD responses in ventral visual pathways, including the MTLs, as compared to the APOE*4+ group. Furthermore, MTL activation was greater during route encoding than survey encoding on average in APOE*4−, but not APOE*4 +, subjects. During recognition, both groups performed similarly and no BOLD signal differences were found. Finally, within-group analysis revealed MTL activation during encoding was correlated with recognition performance in APOE*4−, but not APOE*4+ subjects. Reduced task-associated MTL activation that does not correlate with either visuospatial perspective or task performance suggests that MTL dysregulation occurs prior to clinical symptoms of dementia in APOE*4 carriers.

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“…A similar pattern of cerebral hypometabolism was also detected between patients with APOE 4 -positive and -negative AD but with stronger abnormalities in 4 carriers in the parietal, temporal, and posterior cingulate cortical regions. 18 Recently Ossenkoppele et al 19 found a reversed APOE 4 dose effect for amyloid deposition in the frontal lobe, whereas APOE 4 carriership was associated with more profound metabolic impairment in the posterior parts of the cortex. These findings suggest that the APOE genotype has a differential effect on the distribution of amyloid plaques and glucose metabolism.…”

Section: Effects Of Apoe On Fdg-pet and Amyloid Imaging Of Alzheimer mentioning

confidence: 99%

“…Because the half-life of the 11 C isotope is short, 11 C-PiB is available only in specific institutions that have a cyclotron and a synthesis system. Conversely, the half-life of the 18 F isotope is 110 minutes, and 18 F-labeled amyloid imaging tracers will become widely used following production by radiopharmaceutical companies. Currently there are a few 18 F-labeled amyloid imaging tracers available (Table 1), 29 though in 2012, 18 F-AV-45 (florbetapir) 30 was approved by the FDA for PET imaging of ␤-amyloid neuritic plaques in the living brain.…”

Section: Amyloid Imaging In Alzheimer Diseasementioning

confidence: 99%

“…Neurofibrillary tangles are preferentially located in the hippocampus and associative cortical regions. 18 F-2-(1-{6-[(2-[F]Fluoroethyl)(methyl)amino]-2-naphthyl}-ethylidene)malononitrile or FDDNP was initially developed for A␤ imaging, though this ligand binds to both A␤ plaques and neurofibrillary tangles in the brain. As such, FDDNP was expected to demonstrate both amyloid and neurofibrillary tangle deposits 61 but has limited value for accurate measurement of -related pathology in patients with AD.…”

Section: Tau Imagingmentioning

confidence: 99%

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PET Approaches for Diagnosis of Dementia

Ishii

2013

AJNR Am J Neuroradiol

101

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SUMMARY:There is increasing use of neuroimaging modalities, including PET, for diagnosing dementia. For example, FDG-PET demonstrates hypometabolic regions in the posterior cingulate gyri, precuneus, and parietotemporal association cortices, while amyloid PET indicates amyloid deposition in Alzheimer disease and mild cognitive impairment due to Alzheimer disease. Furthermore, the use of combination PET with structural MR imaging can improve the diagnostic accuracy of dementia. In other neurodegenerative dementias, each disease exhibits a specific metabolic reduction pattern. In dementia with Lewy bodies, occipital glucose metabolism is decreased, while in frontotemporal dementia, frontal and anterior temporal metabolism is predominantly decreased. These FDG-PET findings and positive or negative amyloid deposits are important biomarkers for various neurodegenerative dementias. ABBREVIATIONS:A␤ ϭ amyloid ␤ peptide; AD ϭ Alzheimer disease; APOE ϭ apolipoprotein E; CBD ϭ corticobasal degeneration; DLB ϭ dementia with Lewy

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Cerebral glucose metabolism in patients with AD and different APOE genotypes

Abstract: A generally similar pattern of cerebral hypometabolism was detected in APOE epsilon4-positive and -negative patients with Alzheimer disease. However, in direct comparison of the two matched groups, the abnormalities in the epsilon4-positive group were demonstrated to be more pronounced.

Cited by 109 publications

References 38 publications

Maternal family history of Alzheimer's disease predisposes to reduced brain glucose metabolism

Maternal family history of Alzheimer's disease predisposes to reduced brain glucose metabolism

Altered medial temporal lobe responses during visuospatial encoding in healthy APOE*4 carriers

PET Approaches for Diagnosis of Dementia

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