Prevalence of amyloid PET positivity in dementia syndromes: a meta-analysis

Abstract

Importance: Amyloid-β positron emission tomography (PET) imaging allows in vivo detection of fibrillar plaques, a core neuropathological feature of Alzheimer disease (AD). Its diagnostic utility is still unclear because amyloid plaques also occur in patients with non-AD dementia.

Objective: To use individual participant data meta-analysis to estimate the prevalence of amyloid positivity on PET in a wide variety of dementia syndromes.

Data sources: The MEDLINE and Web of Science databases were searched from January 2004 to April 2015 for amyloid PET studies.

Study selection: Case reports and studies on neurological or psychiatric diseases other than dementia were excluded. Corresponding authors of eligible cohorts were invited to provide individual participant data.

Data extraction and synthesis: Data were provided for 1359 participants with clinically diagnosed AD and 538 participants with non-AD dementia. The reference groups were 1849 healthy control participants (based on amyloid PET) and an independent sample of 1369 AD participants (based on autopsy).

Main outcomes and measures: Estimated prevalence of positive amyloid PET scans according to diagnosis, age, and apolipoprotein E (APOE) ε4 status, using the generalized estimating equations method.

Results: The likelihood of amyloid positivity was associated with age and APOE ε4 status. In AD dementia, the prevalence of amyloid positivity decreased from age 50 to 90 years in APOE ε4 noncarriers (86% [95% CI, 73%-94%] at 50 years to 68% [95% CI, 57%-77%] at 90 years; n = 377) and to a lesser degree in APOE ε4 carriers (97% [95% CI, 92%-99%] at 50 years to 90% [95% CI, 83%-94%] at 90 years; n = 593; P < .01). Similar associations of age and APOE ε4 with amyloid positivity were observed in participants with AD dementia at autopsy. In most non-AD dementias, amyloid positivity increased with both age (from 60 to 80 years) and APOE ε4 carriership (dementia with Lewy bodies: carriers [n = 16], 63% [95% CI, 48%-80%] at 60 years to 83% [95% CI, 67%-92%] at 80 years; noncarriers [n = 18], 29% [95% CI, 15%-50%] at 60 years to 54% [95% CI, 30%-77%] at 80 years; frontotemporal dementia: carriers [n = 48], 19% [95% CI, 12%-28%] at 60 years to 43% [95% CI, 35%-50%] at 80 years; noncarriers [n = 160], 5% [95% CI, 3%-8%] at 60 years to 14% [95% CI, 11%-18%] at 80 years; vascular dementia: carriers [n = 30], 25% [95% CI, 9%-52%] at 60 years to 64% [95% CI, 49%-77%] at 80 years; noncarriers [n = 77], 7% [95% CI, 3%-18%] at 60 years to 29% [95% CI, 17%-43%] at 80 years.

Conclusions and relevance: Among participants with dementia, the prevalence of amyloid positivity was associated with clinical diagnosis, age, and APOE genotype. These findings indicate the potential clinical utility of amyloid imaging for differential diagnosis in early-onset dementia and to support the clinical diagnosis of participants with AD dementia and noncarrier APOE ε4 status who are older than 70 years.

Figure 1. Flow Diagram of Participant Selection for Dementia Syndromes

MCI indicates mild cognitive impairment. MEDLINE and Web of Science databases were searched from January 2004 to April 2015.

Figure 2. Prevalence of Amyloid Positivity on PET According to Age for the Different Dementia Diagnostic Groups

PET indicates positron emission tomography. The curves were plotted using the point estimates generated by generalized estimating equations and are within the age limits of the diagnostic groups. The models were adjusted for study effects. The 95% CIs are presented in Table 2 and eFigure 3 in the Supplement.

Figure 3. Relative Odds of Non–Alzheimer Dementias vs Alzheimer Dementia

AD indicates Alzheimer disease. The curves were plotted using the point estimates generated by generalized estimating equations and represent odds ratios of amyloid positivity for the different non–AD dementia syndromes (with patients with AD dementia as the reference group) as a function of age. The models include amyloid status on PET (positive or negative), age (as a continuous variable), and an interaction between amyloid status and age. The curves are within the age limits of the diagnostic groups.