FDG-PET changes in brain glucose metabolism from normal cognition to pathologically verified Alzheimer's disease

Abstract

Purpose: We report the first clinicopathological series of longitudinal FDG-PET scans in post-mortem (PM) verified cognitively normal elderly (NL) followed to the onset of Alzheimer's-type dementia (DAT), and in patients with mild DAT with progressive cognitive deterioration.

Methods: Four NL subjects and three patients with mild DAT received longitudinal clinical, neuropsychological and dynamic FDG-PET examinations with arterial input functions. NL subjects were followed for 13 +/- 5 years, received FDG-PET examinations over 7 +/- 2 years, and autopsy 6 +/- 3 years after the last FDG-PET. Two NL declined to mild cognitive impairment (MCI), and two developed probable DAT before death. DAT patients were followed for 9 +/- 3 years, received FDG-PET examinations over 3 +/- 2 years, and autopsy 7 +/- 1 years after the last FDG-PET. Two DAT patients progressed to moderate-to-severe dementia and one developed vascular dementia.

Results: The two NL subjects who declined to DAT received a PM diagnosis of definite AD. Their FDG-PET scans indicated a progression of deficits in the cerebral metabolic rate for glucose (CMRglc) from the hippocampus to the parietotemporal and posterior cingulate cortices. One DAT patient showed AD with diffuse Lewy body disease (LBD) at PM, and her last in vivo PET was indicative of possible LBD for the presence of occipital as well as parietotemporal hypometabolism.

Conclusion: Progressive CMRglc reductions on FDG-PET occur years in advance of clinical DAT symptoms in patients with pathologically verified disease. The FDG-PET profiles in life were consistent with the PM diagnosis.

Fig. 1

Progression of CMRglc abnormalities in patient 1 who declined from normal cognition to MCI and received a postmortem diagnosis of probable AD. a 3D-SSP maps and corresponding Z scores reflecting CMRglc reductions in the patient as compared with the normative database are displayed using a color-coded scale ranging from 0 (black)to 6(red) on the right and left lateral, superior, inferior, anterior, posterior, right and left medial views of a standardized brain template image. b Regional CMRglc values at each timepoint are compared to reference control values (white; error bars are standard errors) [25]. *p≤ 0.05 vs controls (IPL inferior parietal lobe, HIP hippocampus, LTL lateral temporal lobe, PCC posterior cingulate cortex, FCx frontal cortex; L left, R right hemisphere)

fig. 2

Progression of CMRglc abnormalities in patient 2 who declined from normal cognition to MCI and received a postmortem diagnosis of Parkinson's disease with additional AD-related pathological lesions. a, b See legend to Fig. 1

Fig. 3

Progression of CMRglc abnormalities in patient 3 who declined from normal cognition to DAT and received a postmortem diagnosis of definite AD. a, b See legend to Fig. 1

Fig. 4

Progression of CMRglc abnormalities in patient 4 who declined from normal cognition to DAT and received a postmortem diagnosis of definite AD. a, b See legend to Fig. 1. c Original FDG-PET scans are displayed as transaxial slices 10 mm apart from the bottom (left) to the top (right) of the brain. CMRglc values are displayed on a color-coded scale ranging from 0 to 50 μmol/ 100 g per minute

Fig. 5

Progression of CMRglc abnormalities in patient 5 who progressed from mild to severe DAT in life, and received a postmortem diagnosis of definite AD. a, b See legend to Fig. 1

Fig. 6

Progression of CMRglc abnormalities in patient 6 who progressed from mild DAT to probable vascular dementia in life and received a post-mortem diagnosis of definite AD. a, b See legend to Fig. 1

Fig. 7

Progression of CMRglc abnormalities in patient 7 who progressed from mild to moderate DAT in life and received a post-mortem diagnosis of definite AD. a, b See legend to Fig. 1