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FDG and Amyloid PET in Cognitively Normal Individuals at Risk for Late-Onset Alzheimer's Disease.
Adv J Mol Imaging. 2014 Apr; 4(2):15-26.AJ

Abstract

Having a parent affected by late-onset Alzheimer's disease (AD) is a major risk factor for cognitively normal (NL) individuals. This study explores the potential of PET with 18F-FDG and the amyloid- β (Aβ) tracer 11C-Pittsburgh Compound B (PiB) for detection of individual risk in NL adults with AD-parents.

METHODS

FDG- and PiB-PET was performed in 119 young to late-middle aged NL individuals including 80 NL with positive family history of AD (FH+) and 39 NL with negative family history of any dementia (FH-). The FH+ group included 50 subjects with maternal (FHm) and 30 with paternal family history (FHp). Individual FDG and PiB scans were Z scored on a voxel-wise basis relative to modality-specific reference databases using automated procedures and rated as positive or negative (+/-) for AD-typical abnormalities using predefined criteria. To determine the effect of age, the cohort was separated into younger (49 ± 9 y) and older (68 ± 5 y) groups relative to the median age (60 y).

RESULTS

Among individuals of age >60 y, as compared to controls, NL FH+ showed a higher frequency of FDG+ scans vs. FH- (53% vs. 6% p < 0.003), and a trend for PiB+ scans (27% vs. 11%; p = 0.19). This effect was observed for both FHm and FHp groups. Among individuals of age ≤60 y, NL FHm showed a higher frequency of FDG+ scans (29%) compared to FH- (5%, p = 0.04) and a trend compared to FHp (11%) (p = 0.07), while the distribution of PiB+ scans was not different between groups. In both age cohorts, FDG+ scans were more frequent than PiB+ scans among NL FH+, especially FHm (p < 0.03). FDG-PET was a significant predictor of FH+ status. Classification according to PiB status was significantly less successful.

CONCLUSIONS

Automated analysis of FDG- and PiB-PET demonstrates higher rates of abnormalities in at-risk FH+ vs FH- subjects, indicating potentially ongoing early AD-pathology in this population. The frequency of metabolic abnormalities was higher than that of Aβ pathology in the younger cohort, suggesting that neuronal dysfunction may precede major aggregated Aβ burden in young NL FH+. Longitudinal follow-up is required to determine if the observed abnormalities predict future AD.

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Authors+Show Affiliations

Murray J
New York University School of Medicine, New York, USA.
Tsui WH
New York University School of Medicine, New York, USA.
Li Y
New York University School of Medicine, New York, USA.
McHugh P
New York University School of Medicine, New York, USA.
Williams S
New York University School of Medicine, New York, USA.
Cummings M
New York University School of Medicine, New York, USA.
Pirraglia E
New York University School of Medicine, New York, USA.
Solnes L
Weill Cornell Medical College, New York, USA.
Osorio R
New York University School of Medicine, New York, USA.
Glodzik L
New York University School of Medicine, New York, USA.
Vallabhajosula S
Weill Cornell Medical College, New York, USA.
Drzezga A
University of Cologne, Cologne, Germany.
Minoshima S
University of Washington, Seattle, USA.
de Leon MJ
New York University School of Medicine, New York, USA.
Mosconi L
New York University School of Medicine, New York, USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

25530915

Citation

Murray, John, et al. "FDG and Amyloid PET in Cognitively Normal Individuals at Risk for Late-Onset Alzheimer's Disease." Advances in Molecular Imaging, vol. 4, no. 2, 2014, pp. 15-26.
Murray J, Tsui WH, Li Y, et al. FDG and Amyloid PET in Cognitively Normal Individuals at Risk for Late-Onset Alzheimer's Disease. Adv J Mol Imaging. 2014;4(2):15-26.
Murray, J., Tsui, W. H., Li, Y., McHugh, P., Williams, S., Cummings, M., Pirraglia, E., Solnes, L., Osorio, R., Glodzik, L., Vallabhajosula, S., Drzezga, A., Minoshima, S., de Leon, M. J., & Mosconi, L. (2014). FDG and Amyloid PET in Cognitively Normal Individuals at Risk for Late-Onset Alzheimer's Disease. Advances in Molecular Imaging, 4(2), 15-26.
Murray J, et al. FDG and Amyloid PET in Cognitively Normal Individuals at Risk for Late-Onset Alzheimer's Disease. Adv J Mol Imaging. 2014;4(2):15-26. PubMed PMID: 25530915.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - FDG and Amyloid PET in Cognitively Normal Individuals at Risk for Late-Onset Alzheimer's Disease. AU - Murray,John, AU - Tsui,Wai H, AU - Li,Yi, AU - McHugh,Pauline, AU - Williams,Schantel, AU - Cummings,Megan, AU - Pirraglia,Elizabeth, AU - Solnes,Lilja, AU - Osorio,Ricardo, AU - Glodzik,Lidia, AU - Vallabhajosula,Shankar, AU - Drzezga,Alexander, AU - Minoshima,Satoshi, AU - de Leon,Mony J, AU - Mosconi,Lisa, PY - 2014/12/23/entrez PY - 2014/12/23/pubmed PY - 2014/12/23/medline KW - Alzheimer’s Disease KW - Amyloid Imaging KW - Early Detection KW - Glucose Metabolism KW - Normal Aging KW - Positron Emission Tomography SP - 15 EP - 26 JF - Advances in molecular imaging JO - Adv J Mol Imaging VL - 4 IS - 2 N2 - : Having a parent affected by late-onset Alzheimer's disease (AD) is a major risk factor for cognitively normal (NL) individuals. This study explores the potential of PET with 18F-FDG and the amyloid- β (Aβ) tracer 11C-Pittsburgh Compound B (PiB) for detection of individual risk in NL adults with AD-parents. METHODS: FDG- and PiB-PET was performed in 119 young to late-middle aged NL individuals including 80 NL with positive family history of AD (FH+) and 39 NL with negative family history of any dementia (FH-). The FH+ group included 50 subjects with maternal (FHm) and 30 with paternal family history (FHp). Individual FDG and PiB scans were Z scored on a voxel-wise basis relative to modality-specific reference databases using automated procedures and rated as positive or negative (+/-) for AD-typical abnormalities using predefined criteria. To determine the effect of age, the cohort was separated into younger (49 ± 9 y) and older (68 ± 5 y) groups relative to the median age (60 y). RESULTS: Among individuals of age >60 y, as compared to controls, NL FH+ showed a higher frequency of FDG+ scans vs. FH- (53% vs. 6% p < 0.003), and a trend for PiB+ scans (27% vs. 11%; p = 0.19). This effect was observed for both FHm and FHp groups. Among individuals of age ≤60 y, NL FHm showed a higher frequency of FDG+ scans (29%) compared to FH- (5%, p = 0.04) and a trend compared to FHp (11%) (p = 0.07), while the distribution of PiB+ scans was not different between groups. In both age cohorts, FDG+ scans were more frequent than PiB+ scans among NL FH+, especially FHm (p < 0.03). FDG-PET was a significant predictor of FH+ status. Classification according to PiB status was significantly less successful. CONCLUSIONS: Automated analysis of FDG- and PiB-PET demonstrates higher rates of abnormalities in at-risk FH+ vs FH- subjects, indicating potentially ongoing early AD-pathology in this population. The frequency of metabolic abnormalities was higher than that of Aβ pathology in the younger cohort, suggesting that neuronal dysfunction may precede major aggregated Aβ burden in young NL FH+. Longitudinal follow-up is required to determine if the observed abnormalities predict future AD. SN - 2161-6728 UR - https://www.unboundmedicine.com/medline/citation/25530915/FDG_and_Amyloid_PET_in_Cognitively_Normal_Individuals_at_Risk_for_Late_Onset_Alzheimer's_Disease_ DB - PRIME DP - Unbound Medicine ER -