Brain amyloidosis is associated with worse cognitive performance in both the cognitively normal and impaired stages: A [18F]flutemetamol PET study


      Alzheimer’s pathology develops gradually over time and the latent stages of the disease often go undetected. The Mini Mental State Examination (MMSE) is generally thought to be insensitive in meaningfully capturing cognitive decline during the presymptomatic stages.


      To explore the relationship between [18F]Flutemetamol binding and MMSE in cognitively normal and cognitively impaired individuals.


      MMSE and [18F]Flutemetamol PET were administered to 34 and 64 cognitively normal elderly at UCLA (UCLA-NC) and University of Leuven (Leuven-NC), respectively. [18F]Flutemetamol mean standard uptake volume ratios (SUVR) (Clark method), as well as mean lobar and basal ganglia (BG) SUVR measurements were obtained. We used linear regression to study the association between MMSE and SUVR measures. We repeated the analyses after the inclusion of 19 MCI and 12 dementia UCLA subjects. All regression analyses were adjusted for age, education and ApoE4 genotype.


      Compared to Leuven-NC, UCLA-NC were on average older (75.8 vs. 65.3 years, p<0.0001) and more educated (16.5 vs. 13.6 years, p=0.001). There were no differences in gender, ApoE4 genotype distribution, MMSE, mean or lobar SUVR. Leuven-NC had significantly higher BG SUVR (1.5 vs. 1.3, p=0.0002). Parietal SUVR was the single amyloid measure that predicted MMSE (beta coefficient =1.2, p=0.045). Mixed effect linear regression with random subject and fixed MMSE effects showed that for each unit decline in MMSE parietal and posterior cingulate SUVR increased by 0.04 (p=0.047) and 0.05 (p=0.02), respectively. In the combined analyses one unit decline in MMSE was associated with significant increase in cingulate SUVR in all three diagnostic categories (UCLA/Leuven-NC ΔSUVR=0.06, p=0.01; MCI ΔSUVR=0.13, p<0.0001; dementia ΔSUVR=0.04, p=0.0007). An effect was also seen for parietal SUVR in MCI (ΔSUVR=0.1, p=0.0004) and UCLA/Leuven-NC (ΔSUVR=0.05, p=0.04) as well as in frontal (ΔSUVR=0.09, p=0.0006) temporal (ΔSUVR=0.08, p=0.005), occipital (ΔSUVR=0.1, p=0.0004) and basal ganglia (ΔSUVR=0.08, p=0.0016) SUVR in MCI only.


      Higher SUVR is associated with worse cognitive performance in both the cognitively normal and impaired stages. Most significant SUVR increases per unit MMSE were seen in MCI, followed by NC and finally demented subjects in agreement with the sigmoid curve of increasing amyloid deposition.