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

beta-amyloid (A beta) 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 A beta burden in non-demented persons and in AD patients is unclear. We examined this relationship using C-11-PIB-PET as a quantitative marker of A beta 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 C-11-PIB-PET brain scan. Multiple linear regression analyses were conducted relating episodic memory performance and other cognitive functions to A beta burden. Ninety-seven percent of AD, 61% of MCI and 22% of HA cases had increased cortical PIB binding, indicating the presence of A beta 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. A beta 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 A beta deposition are warranted.