Amyloid Deposition, Hypometabolism, and Longitudinal Cognitive Decline

Overview

Journal Ann Neurol

Specialty Neurology

Date 2012 Oct 31

PMID 23109153

Citations 385

Authors

Susan M Landau

Mark A Mintun

Abhinay D Joshi

Robert A Koeppe

Ronald C Petersen

Paul S Aisen

Michael W Weiner

William J Jagust

Affiliations

Soon will be listed here.

Abstract

Objective: Using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) population, we examined (1) cross-sectional relationships between amyloid deposition, hypometabolism, and cognition, and (2) associations between amyloid and hypometabolism measurements and longitudinal cognitive measurements.

Methods: We examined associations between mean cortical florbetapir uptake, mean (18) F-fluorodeoxyglucose-positron emission tomography (FDG-PET) within a set of predefined regions, and Alzhiemer's Disease Assessment Scale (ADAS-cog) performance in 426 ADNI participants (126 normal, 162 early mild cognitive impairment [EMCI], 85 late MCI [LMCI], 53 Alzheimer disease [AD] patients). For a subset of these (76 normal, 81 LMCI) we determined whether florbetapir and FDG-PET were associated with retrospective decline in longitudinal ADAS-cog measurements.

Results: Twenty-nine percent of normal subjects, 43% of EMCI patients, 62% of LMCI patients, and 77% of AD patients were categorized as florbetapir positive. Florbetapir was negatively associated with concurrent FDG and ADAS-cog in both MCI groups. In longitudinal analyses, florbetapir-positive subjects in both normal and LMCI groups had greater ongoing ADAS-cog decline than those who were florbetapir negative. However, in normal subjects, florbetapir positivity was associated with greater ADAS-cog decline than FDG, whereas in LMCI, FDG positivity was associated with greater decline than florbetapir.

Interpretation: Although both hypometabolism and β-amyloid (Aβ) deposition are detectable in normal subjects and all diagnostic groups, Aβ showed greater associations with cognitive decline in normal participants. In view of the minimal cognitive deterioration overall in this group, this suggests that amyloid deposition has an early and subclinical impact on cognition that precedes metabolic changes. At moderate and later stages of disease (LMCI/AD), hypometabolism becomes more pronounced and more closely linked to ongoing cognitive decline.

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References

Mormino E, Kluth J, Madison C, Rabinovici G, Baker S, Miller B . Episodic memory loss is related to hippocampal-mediated beta-amyloid deposition in elderly subjects. Brain. 2008; 132(Pt 5):1310-23. PMC: 2677792. DOI: 10.1093/brain/awn320. View

Pearl G . Diagnosis of Alzheimer's disease in a community hospital-based brain bank program. South Med J. 1997; 90(7):720-2. DOI: 10.1097/00007611-199707000-00013. View

Mintun M, Larossa G, Sheline Y, Dence C, Lee S, Mach R . [11C]PIB in a nondemented population: potential antecedent marker of Alzheimer disease. Neurology. 2006; 67(3):446-52. DOI: 10.1212/01.wnl.0000228230.26044.a4. View

Rabinovici G, Rosen H, Alkalay A, Kornak J, Furst A, Agarwal N . Amyloid vs FDG-PET in the differential diagnosis of AD and FTLD. Neurology. 2011; 77(23):2034-42. PMC: 3236517. DOI: 10.1212/WNL.0b013e31823b9c5e. View

Forster S, Grimmer T, Miederer I, Henriksen G, Yousefi B, Graner P . Regional expansion of hypometabolism in Alzheimer's disease follows amyloid deposition with temporal delay. Biol Psychiatry. 2011; 71(9):792-7. DOI: 10.1016/j.biopsych.2011.04.023. View

Reiman E, Chen K, Alexander G, Caselli R, Bandy D, Osborne D . Functional brain abnormalities in young adults at genetic risk for late-onset Alzheimer's dementia. Proc Natl Acad Sci U S A. 2003; 101(1):284-9. PMC: 314177. DOI: 10.1073/pnas.2635903100. View

Joshi A, Pontecorvo M, Clark C, Carpenter A, Jennings D, Sadowsky C . Performance characteristics of amyloid PET with florbetapir F 18 in patients with alzheimer's disease and cognitively normal subjects. J Nucl Med. 2012; 53(3):378-84. DOI: 10.2967/jnumed.111.090340. View

Ewers M, Insel P, Jagust W, Shaw L, Trojanowski J, Aisen P . CSF biomarker and PIB-PET-derived beta-amyloid signature predicts metabolic, gray matter, and cognitive changes in nondemented subjects. Cereb Cortex. 2011; 22(9):1993-2004. PMC: 3500862. DOI: 10.1093/cercor/bhr271. View

Lim A, Tsuang D, Kukull W, Nochlin D, Leverenz J, McCormick W . Clinico-neuropathological correlation of Alzheimer's disease in a community-based case series. J Am Geriatr Soc. 1999; 47(5):564-9. DOI: 10.1111/j.1532-5415.1999.tb02571.x. View

10.

Chetelat G, Villemagne V, Pike K, Ellis K, Ames D, Masters C . Relationship between memory performance and β-amyloid deposition at different stages of Alzheimer's disease. Neurodegener Dis. 2012; 10(1-4):141-4. DOI: 10.1159/000334295. View

11.

Fleisher A, Chen K, Liu X, Roontiva A, Thiyyagura P, Ayutyanont N . Using positron emission tomography and florbetapir F18 to image cortical amyloid in patients with mild cognitive impairment or dementia due to Alzheimer disease. Arch Neurol. 2011; 68(11):1404-11. DOI: 10.1001/archneurol.2011.150. View

12.

Clark C, Schneider J, Bedell B, Beach T, Bilker W, Mintun M . Use of florbetapir-PET for imaging beta-amyloid pathology. JAMA. 2011; 305(3):275-83. PMC: 7041965. DOI: 10.1001/jama.2010.2008. View

13.

Rowe C, Ellis K, Rimajova M, Bourgeat P, Pike K, Jones G . Amyloid imaging results from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging. Neurobiol Aging. 2010; 31(8):1275-83. DOI: 10.1016/j.neurobiolaging.2010.04.007. View

14.

Mosconi L, Mistur R, Switalski R, Tsui W, Glodzik L, Li Y . FDG-PET changes in brain glucose metabolism from normal cognition to pathologically verified Alzheimer's disease. Eur J Nucl Med Mol Imaging. 2009; 36(5):811-22. PMC: 2774795. DOI: 10.1007/s00259-008-1039-z. View

15.

Rodrigue K, Kennedy K, Devous Sr M, Rieck J, Hebrank A, Diaz-Arrastia R . β-Amyloid burden in healthy aging: regional distribution and cognitive consequences. Neurology. 2012; 78(6):387-95. PMC: 3280058. DOI: 10.1212/WNL.0b013e318245d295. View

16.

Shimada H, Ataka S, Takeuchi J, Mori H, Wada Y, Watanabe Y . Pittsburgh compound B-negative dementia: a possibility of misdiagnosis of patients with non-alzheimer disease-type dementia as having AD. J Geriatr Psychiatry Neurol. 2011; 24(3):123-6. DOI: 10.1177/0891988711409410. View

17.

Landau S, Harvey D, Madison C, Reiman E, Foster N, Aisen P . Comparing predictors of conversion and decline in mild cognitive impairment. Neurology. 2010; 75(3):230-8. PMC: 2906178. DOI: 10.1212/WNL.0b013e3181e8e8b8. View

18.

Edison P, Archer H, Hinz R, Hammers A, Pavese N, Tai Y . Amyloid, hypometabolism, and cognition in Alzheimer disease: an [11C]PIB and [18F]FDG PET study. Neurology. 2006; 68(7):501-8. DOI: 10.1212/01.wnl.0000244749.20056.d4. View

19.

Villemagne V, Pike K, Chetelat G, Ellis K, Mulligan R, Bourgeat P . Longitudinal assessment of Aβ and cognition in aging and Alzheimer disease. Ann Neurol. 2011; 69(1):181-92. PMC: 3045039. DOI: 10.1002/ana.22248. View

20.

Jagust W, Landau S, Shaw L, Trojanowski J, Koeppe R, Reiman E . Relationships between biomarkers in aging and dementia. Neurology. 2009; 73(15):1193-9. PMC: 2764726. DOI: 10.1212/WNL.0b013e3181bc010c. View