Prevalence of Cerebral Amyloid Pathology in Persons Without Dementia

By Willemijn J. Jansen, Rik Ossenkoppele, Dirk L. Knol, B. Tijms, Philip Scheltens, F. Verhey, Pieter Jelle Visser. Journal of the American Medical Association (JAMA), 2015

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IMPORTANCE Cerebral amyloid-β aggregation is an early pathological event in Alzheimer disease (AD), starting decades before dementia onset. Estimates of the prevalence of amyloid pathology in persons without dementia are needed to understand the development of AD and to design prevention studies. OBJECTIVE To use individual participant data meta-analysis to estimate the prevalence of amyloid pathology as measured with biomarkers in participants with normal cognition, subjective cognitive impairment (SCI), or mild cognitive impairment (MCI). DATA SOURCES Relevant biomarker studies identified by searching studies published before April 2015 using the MEDLINE and Web of Science databases and through personal communication with investigators. STUDY SELECTION Studies were included if they provided individual participant data for participants without dementia and used an a priori defined cutoff for amyloid positivity. DATA EXTRACTION AND SYNTHESIS Individual records were provided for 2914 participants with normal cognition, 697 with SCI, and 3972 with MCI aged 18 to 100 years from 55 studies. MAIN OUTCOMES AND MEASURES Prevalence of amyloid pathology on positron emission tomography or in cerebrospinal fluid according to AD risk factors (age, apolipoprotein E [APOE] genotype, sex, and education) estimated by generalized estimating equations. RESULTS The prevalence of amyloid pathology increased from age 50 to 90 years from 10% (95% CI, 8%-13%) to 44% (95% CI, 37%-51%) among participants with normal cognition; from 12% (95% CI, 8%-18%) to 43% (95% CI, 32%-55%) among patients with SCI; and from 27% (95% CI, 23%-32%) to 71% (95% CI, 66%-76%) among patients with MCI. APOE-ε4 carriers had 2 to 3 times higher prevalence estimates than noncarriers. The age at which 15% of the participants with normal cognition were amyloid positive was approximately 40 years for APOEε4ε4 carriers, 50 years for ε2ε4 carriers, 55 years for ε3ε4 carriers, 65 years for ε3ε3 carriers, and 95 years for ε2ε3 carriers. Amyloid positivity was more common in highly educated participants but not associated with sex or biomarker modality. CONCLUSIONS AND RELEVANCE Among persons without dementia, the prevalence of cerebral amyloid pathology as determined by positron emission tomography or cerebrospinal fluid findings was associated with age, APOEgenotype, and presence of cognitive impairment. These findings suggest a 20- to 30-year interval between first development of amyloid positivity and onset of dementia.

Subfields: Neurology, Physiology, Psychiatry and Mental health

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Citations in the corpus

Clinical diagnosis of Alzheimer’s disease: recommendations of the International Working Group (2021, result): “In this regard, it is noteworthy that the frequency of CSF AD profiles between those with normal cognition and SMC is similar 58 .”
Clinical Neurology and Epidemiology of the Major Neurodegenerative Diseases. (2018, background): “Although amyloid-PET imaging can reliably detect the presence or absence of amyloid with high sensitivity, amyloid commonly is found in elderly patients even without cognitive impairment (30%–40% at age 80) (Jansen et al. 2015; Ossenkoppele et al. 2015a).”
Preclinical Alzheimer’s disease: Definition, natural history, and diagnostic criteria (2016, background): “A recent meta-analysis estimated the prevalence of Ab biomarker positivity (as defined by either CSFAb42 or amyloid PET) in nearly 3000 cognitively normal individuals [46].”
Tau PET patterns mirror clinical and neuroanatomical variability in Alzheimer's disease. (2016, background): “Age-related comorbid amyloid-b pathology is unusual at the patient’s age (16–18% across cognitively normal persons aged 60; Jack et al., 2014; Jansen et al., 2015) and Alzheimer’s disease path- ology may be a more frequent cause of corticobasal syn- drome in young patients (Ossenkoppele et al.,…”