Amyloid deposition, hypometabolism, and longitudinal cognitive decline

• Published in: Annals of neurology Vol. 72; no. 4; pp. 578 - 586
• Main Authors: Landau, Susan M., Mintun, Mark A., Joshi, Abhinay D., Koeppe, Robert A., Petersen, Ronald C., Aisen, Paul S., Weiner, Michael W., Jagust, William J.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01-10-2012; Wiley-Liss; Wiley Subscription Services, Inc
• Subjects: Aged; Alzheimer's disease; Amyloid - metabolism; Aniline Compounds; Biological and medical sciences; Body Burden; Cognition & reasoning; Cognition Disorders - diagnostic imaging; Cognition Disorders - metabolism; Cognition Disorders - psychology; Cognitive Dysfunction - pathology; Cognitive Dysfunction - psychology; Cross-Sectional Studies; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Disease Progression; Ethylene Glycols; Female; Fluorodeoxyglucose F18; Humans; Image Processing, Computer-Assisted; Longitudinal Studies; Male; Medical sciences; Middle Aged; Neurology; Neuropsychological Tests; Positron-Emission Tomography; Nervous system diseases; Amyloid; Cognitive disorder
• ISSN: 0364-5134; 1531-8249
• DOI: 10.1002/ana.23650

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 18F‐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. ANN NEUROL 2012;72:578–586