J Alzheimers Dis. 2017;57(3):765-773. doi: 10.3233/JAD-161074.

AmyloidDeposition and Long-Term Progression in Mild Cognitive Impairment due to Alzheimer’s Disease Defined with Amyloid PET Imaging.

Hatashita S1, Wakebe D2.

1 Neurology, Shonan Atsugi Hospital, Atsugi, Japan.
2 Radiology, Shonan Atsugi Hospital, Atsugi, Japan.

Abstract

The aim was to evaluate brain amyloid-β (Aβ) deposition in patients with mild cognitive impairment (MCI) due to Alzheimer’s disease (AD) using amyloid PET imaging and clarify the relationship between the annual change in Aβ deposition and disease progression. Forty-eight MCI patients underwent neuropsychological assessment and amyloid PET imaging using [11C]-PIB over a follow-up of 5.7±1.5 years. Thirty-nine MCI patients who had an amyloid-positive scan were defined as MCI due to AD, and 9 MCI patients who had an amyloid-negative scan were included. Regions of interest were defined on co-registered MRI, and the PIB standardized uptake value ratio (SUVR) on the same regions was used over follow-up. Annual change in PIB SUVR was calculated. Patients with MCI due to AD had higher baseline PIB SUVR (1.81±0.32, n = 39, p < 0.01) and a greater annual rate of change in PIB SUVR (0.044±0.027, n = 39, p < 0.01) compared to amyloid-negative MCI patients. Twenty-eight (71.8%) progressed to AD. In patients who progressed during a short duration of 1.7±0.8 years, the annual rate of increase in PIB SUVR was 0.101±0.094 (n = 16, p < 0.05), which was greater compared to patients with long conversion or stable patients. There was a negative correlation between the annual rate of increase in PIB SUVR and duration of progression to AD among individual MCI converters (r = -0.47, n = 28, p < 0.05). The patients defined as MCI due to AD could progress to AD with a shorter period if they have a greater increased annual rate in brain Aβ deposition.

KEYWORDS:

Alzheimer’s disease; amyloid PET imaging; amyloid-β; mild cognitive impairment; progression

PMID: 28304292

 

Supplement:  

We demonstrate that 16 (41.0%) of the 39 patients who were identified by [11C]-PIB PET as MCI due to AD progressed to AD dementia within 3 years and 26 (78.7%) of 33 patients progressed within 6 years. The pattern of the consecutive progression rate of MCI due to AD to AD dementia best fit a curvilinear regression line (Figure). The patients with MCI due to AD could progress to AD dementia if they are defined with amyloid PET.

The present study found that the cortical PIB SUVR at baseline was significantly higher in MCI patients who progressed to AD over a short-term follow-up of 1.7±0.8 years than that in patients ho progressed over a long-term follow-up of 4.4±1.1 years or in patients who did not progress. In addition, the annual rate of increase of PIB SUVR was greater in patients with short-term progression. The annual increase of PIB SUVR was significantly correlated to the period of MCI progression to AD. These findings indicate that the patients with MCI due to AD quickly progress to AD when they have greater increased annual rate in Aβ deposition in addition to higher brain Aβ deposition at baseline.

Furthermore, the present study showed that patients with MCI due to AD had greater rate of increases in brain Aβ deposition during the process of progression to AD, followed by smaller rates of increase in Aβ deposition at AD stage. An annual rate of increase in Aβ deposition was significantly correlated to an annual rate of decline in MMSE scores among the MCI patients until the progression to AD. It is suggested that the greater rate of increase in Aβ deposition accelerates cognitive decline and progression from MCI to AD.

If the rate of new Aβ production or volume of Aβ deposition is reduced by the Aβ-lowing strategies in the asymptomatic stage of AD spectrum, brain Aβ deposition could be smaller, leading to potentially slower progression to AD.