The consequences of Aβ deposition in ageing and Alzheimer’s disease: Results from 366 elderly subjects

Objectives To study the development of Alzheimer’s disease (AD) in an elderly population by periodical assessment of a spectrum of biochemical and neuroimaging biomarkers.

Methods 366 participants -195 elderly healthy controls (HC) (age 72.2±7.2 years); 92 Mild Cognitive Impairment (MCI) subjects; and 79 mild AD patients, were evaluated at enrolment and 20 and 36 months later, with 5% of participants already reaching the 54-month follow-up mark. On each visit, participants underwent a comprehensive clinical and neuropsychological examination, 3D MRI, and 11C-PiB PET imaging.

Results At baseline, AD and MCI had significantly lower hippocampal volumes than HC, while 98% of AD, 63% of MCI and 34% of HC had high PiB (PiB+). By the latest follow-up of the MCI subjects, 42 met criteria for dementia, (38 AD, 2 dementia with Lewy bodies, 1 frontotemporal dementia, 1 vascular dementia) and 3 were re-classified as HC. Progression to AD occurred in 54% of PiB+ MCI vs. 14% of PiB- MCI, while 13% of PiB- MCI progressed to other dementias. Of the PiB+ HC, 10% developed MCI and 5% AD by 3 years. Three (2%) PiB- HC developed MCI.

Conclusions Extensive Aβ_ deposition precedes cognitive impairment and is associated with a higher risk of cognitive decline, denoting the non-benign nature of Aβ deposition. Based on our results, there is a >98% (95% CI, 93-99%) chance that an asymptomatic PiB- elderly HC will remain cognitively stable over 3 years in contrast to the 15% risk of developing MCI or AD in PiB+ HC