Evaluation of in vivo staging of amyloid deposition in cognitively unimpaired elderly aged 78–94

Abstract

Amyloid-beta (Aβ) deposition is common in cognitively unimpaired (CU) elderly >85 years. This study investigated amyloid distribution and evaluated three published in vivo amyloid-PET staging schemes from a cognitively unimpaired (CU) cohort aged 84.9 ± 4.3 years (n = 75). SUV-based principal component analysis (PCA) was applied to 18F-flutemetamol PET data to determine an unbiased regional covariance pattern of tracer uptake across grey matter regions. PET staging schemes were applied to the data and compared to the PCA output. Concentration of p-tau181 was measured in blood plasma. The PCA revealed three distinct components accounting for 91.2% of total SUV variance. PC1 driven by the large common variance of uptake in neocortical and striatal regions was significantly positively correlated with global SUVRs, APOE4 status and p-tau181 concentration. PC2 represented mainly non-specific uptake in typical amyloid-PET reference regions, and PC3 the occipital lobe. Application of the staging schemes demonstrated that the majority of the CU cohort (up to 93%) were classified as having pathological amount and distribution of Aβ. Good correspondence existed between binary (+/−) classification and later amyloid stages, however, substantial differences existed between schemes for low stages with 8–17% of individuals being unstageable, i.e., not following the sequential progression of Aβ deposition. In spite of the difference in staging outcomes there was broad spatial overlap between earlier stages and PC1, most prominently in default mode network regions. This study critically evaluated the utility of in vivo amyloid staging from a single PET scan in CU elderly and found that early amyloid stages could not be consistently classified. The majority of the cohort had pathological Aβ, thus, it remains an open topic what constitutes abnormal brain Aβ in the oldest-old and what is the best method to determine that.

Alzheimer’s Amyloid Hypothesis and Antibody Therapy: Melting Glaciers?

“…In another, they ranged from 2.7% in cognitive healthy persons aged 50 to 59 years to 41.3% in those aged 80 to 89 years [19]. Amyloid positivity was also reported in up to 93% of cognitively unimpaired elderly, aged 78-94 [20]. Thus, probably 50% of all cognitively unimpaired elderly persons are amyloid-PET-positive when they die.…”

The use of neuroimaging techniques in the early and differential diagnosis of dementia

“…The use of amyloid PET imaging has several limitations as it does not correlate with symptom onset and disease severity, cannot predict time of onset of dementia syndrome while its use in older populations seem to require more research as amyloid pathology is prevalent in a large proportion of elderly cognitively unimpaired individuals [177]. In summary, amyloid PET is an important tool for the specific diagnosis of AD in the early and preclinical stages, has revolutionised our understanding of the chronology of AD pathophysiology and has opened new therapeutic windows for identification of people more at risk of getting AD and for use in therapeutic AD trials.…”