-amyloid imaging and memory in non-demented individuals: evidence for preclinical Alzheimer's disease

Abstract

Beta-amyloid (Abeta) deposition is pathognomic for Alzheimer's disease (AD), but may occur in normal elderly people without apparent cognitive effect. Episodic memory impairment is an early and prominent sign of AD, but its relationship with Abeta burden in non-demented persons and in AD patients is unclear. We examined this relationship using 11C-PIB-PET as a quantitative marker of Abeta burden in vivo in healthy ageing (HA), mild cognitive impairment (MCI) and AD. Thirty-one AD, 33 MCI and 32 HA participants completed neuropsychological assessment and a 11C-PIB-PET brain scan. Multiple linear regression analyses were conducted relating episodic memory performance and other cognitive functions to Abeta burden. Ninety-seven percent of AD, 61% of MCI and 22% of HA cases had increased cortical PIB binding, indicating the presence of Abeta plaques. There was a strong relationship between impaired episodic memory performance and PIB binding, both in MCI and HA. This relationship was weaker in AD and less robust for non-memory cognitive domains. Abeta deposition in the asymptomatic elderly is associated with episodic memory impairment. This finding, together with the strong relationship between PIB binding and the severity of memory impairment in MCI, suggests that individuals with increased cortical PIB binding are on the path to Alzheimer's disease. The data also suggests that early intervention trials for AD targeted to non-demented individuals with cerebral Abeta deposition are warranted.

Presence of the APOE ε4 allele modifies the relationship between type 2 diabetes and cognitive performance: the Maine–Syracuse Study

“…Thus, the increased insulin levels associated with diabetes may result in less IDE available for the regulation of Aβ [34]. A recent neuroimaging study indicates that Aβ levels are associated with cognitive impairment in non-demented individuals [35]. Furthermore, Alzheimer's disease patients with an APOE ε4 allele exhibit lower levels of IDE in the hippocampus than those without an APOE ε4 allele [36].…”

Effects of theApolipoprotein Eε4 Allele on Functional MRI duringn-Back Working Memory Tasks in Healthy Middle-Aged Adults

“…Numerous studies have proved that amyloid burden can occur many years before objective or subjective cognitive declines, especially among APOE4 carriers. 8,48,49 In the present study, amyloid pathology, which results in brain subclinical dysfunction, might potentially have contributed to the increase in BOLD. Second, the sample size of this study was small.…”

Clearance mechanisms of Alzheimer's amyloid-β peptide: implications for therapeutic design and diagnostic tests

“…42 Interestingly, PIB retention has also been observed in cognitively normal, aged controls and has been associated with episodic memory impairment. 44,45 PIB retention in cognitively healthy aging individuals may therefore be indicative of a pre-clinical disease process.…”