Abstract
Background
We used 72-month longitudinal data from the AIBL study to calculate the rates of Aβ deposition.
Methods
Two-hundred-and-one participants (149HC; 34MCI; 20AD) were evaluated at enrolment and every 18 months for a mean follow-up of 4.9 (range 2.5-10.6) years. On each visit, participants underwent neuropsychological examination, MRI, and a PiB-PET scan. Aβ burden was calculated using the cerebellar cortex as reference region, and 1.4 SUVR (16 Centiloids-CL) was used to discriminate high from low Aβ burdens. Rates of change for Aβ deposition were derived from the slope of the linear regression plots. All participants with positive rates of Aβ deposition, deemed to be on the “AD-pathway,” were used for the analyses.
Results
At baseline higher Aβ burdens were observed in AD (2.3±0.4 SUVR/87±15 CL) and MCI (2.0±0.7 SUVR/64±22 CL) when compared to HC (1.4±0.4 SUVR/16±5 CL). At follow-up 164 (82%) of the participants showed positive rates of Aβ accumulation. Confirming our previous findings but with longer follow-up, Aβ deposition spanned more than two decades, averaging 30 (CI 25-39) years to go from the levels observed in Aβ- HC (1.2±0.1 SUVR/0.6±0.05 CL) to those in mild AD, with rates of 0.048 -CI 0.041-0.056- SUVR/yr or 3.8 -CI 3.2-4.4- CL/yr, between the threshold of PiB abnormality to the levels observed in AD. As dementia progresses, the rate of Aβ deposition slows, approaching a plateau. There were no associations between the rates of Aβ deposition and the rates of hippocampal or grey matter atrophy. There was a significant association between rates of Aβ deposition and rates of episodic memory decline but only in Aβ+ HC accumulators (R2=0.20; p=0.04), an association that disappeared after adjusting for baseline Aβ-burden. ApoE-ε4 carriers had faster accumulation only when <1.4 SUVR (16 CL).
Conclusions
Re-assessment with a longer follow-up confirmed our previous findings that Aβ deposition is a protracted process, likely to extend for more than two decades, even in ε4 carriers. The effects of Aβ accumulation over cognition seem to be limited to the early stages of accumulation suggesting that anti-Aβ therapeutic interventions aimed at modifying the course of AD could be most effective at preclinical stages of the disease.