Prevalence Estimates of Amyloid Abnormality Across the Alzheimer Disease Clinical Spectrum
Por:
Jansen, WJ, Janssen, O, Tijms, BM, Vos, SJB, Ossenkoppele, R, Visser, PJ, Alcolea D., Amyloid Biomarker Study Grp
Publicada:
1 mar 2022
Ahead of Print:
1 ene 2022
Resumen:
IMPORTANCE One characteristic histopathological event in Alzheimer disease (AD) is cerebral amyloid aggregation, which can be detected by biomarkers in cerebrospinal fluid (CSF) and on positron emission tomography (PET) scans. Prevalence estimates of amyloid pathology are important for health care planning and clinical trial design.
OBJECTIVE To estimate the prevalence of amyloid abnormality in persons with normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia and to examine the potential implications of cutoff methods, biomarker modality (CSF or PET), age, sex, APOE genotype, educational level, geographical region, and dementia severity for these estimates.
DESIGN, SETTING, AND PARTICIPANTS This cross-sectional, individual-participant pooled study included participants from 85 Amyloid Biomarker Study cohorts. Data collection was performed from January 1, 2013, to December 31, 2020. Participants had normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia. Normal cognition and subjective cognitive decline were defined by normal scores on cognitive tests, with the presence of cognitive complaints defining subjective cognitive decline. Mild cognitive impairment and clinical AD dementia were diagnosed according to published criteria.
EXPOSURES Alzheimer disease biomarkers detected on PET or in CSF.
MAIN OUTCOMES AND MEASURES Amyloid measurements were dichotomized as normal or abnormal using cohort-provided cutoffs for CSF or PET or by visual reading for PET. Adjusted data-driven cutoffs for abnormal amyloid were calculated using gaussian mixture modeling. Prevalence of amyloid abnormality was estimated according to age, sex, cognitive status, biomarker modality, APOE carrier status, educational level, geographical location, and dementia severity using generalized estimating equations.
RESULTS Among the 19 097 participants (mean [SD] age, 69.1 [9.8] years; 10148 women [53.1%]) included, 10139 (53.1%) underwent an amyloid PET scan and 8958 (46.9%) had an amyloid CSF measurement. Using cohort-provided cutoffs, amyloid abnormality prevalences were similar to 2015 estimates for individuals without dementia and were similar across PETand CSF-based estimates (24%; 95% CI, 21%-28%) in participants with normal cognition, 27% (95% CI, 21%-33%) in participants with subjective cognitive decline, and 51% (95% CI, 46%-56%) in participants with mild cognitive impairment, whereas for dinical AD dementia the estimates were higher for PET than CSF (87% vs 79%; mean difference, 8%; 95% CI, 0%-16%; P = .04). Gaussian mixture modeling-based cutoffs for amyloid measures on PET scans were similar to cohort-provided cutoffs and were not adjusted. Adjusted CSF cutoffs resulted in a 10% higher amyloid abnormality prevalence than PET-based estimates in persons with normal cognition (mean difference, 9%; 95% CI, 3%-15%; P = .004), subjective cognitive decline (9%; 95% CI, 3%-15%; P = .005), and mild cognitive impairment (10%; 95% CI, 3%-17%; P = .004), whereas the estimates were comparable in persons with clinical AD dementia (mean difference, 4%; 95% CI, -2% to 9%; P = .18).
CONCLUSIONS AND RELEVANCE This study found that CSF-based estimates using adjusted data-driven cutoffs were up to 10% higher than PET-based estimates in people without dementia, whereas the results were similar among people with dementia. This finding suggests that preclinical and prodromal AD may be more prevalent than previously estimated, which has important implications for clinical trial recruitment strategies and health care planning policies.
Filiaciones:
Jansen, WJ:
Maastricht Univ, Sch Mental Hlth & Neurosci, Dept Psychiat & Neuropsychol, Alzheimer Ctr Limburg, Maastricht, Netherlands
Banner Alzheimers Inst, Phoenix, AZ 85006 USA
Janssen, O:
Maastricht Univ, Sch Mental Hlth & Neurosci, Dept Psychiat & Neuropsychol, Alzheimer Ctr Limburg, Maastricht, Netherlands
Tijms, BM:
Vrije Univ Amsterdam, Dept Neurol, Alzheimer Ctr Amsterdam, Amsterdam Univ Med Ctr UMC, Amsterdam, Netherlands
Vos, SJB:
Maastricht Univ, Sch Mental Hlth & Neurosci, Dept Psychiat & Neuropsychol, Alzheimer Ctr Limburg, Maastricht, Netherlands
Ossenkoppele, R:
Vrije Univ Amsterdam, Dept Neurol, Alzheimer Ctr Amsterdam, Amsterdam Univ Med Ctr UMC, Amsterdam, Netherlands
Lund Univ, Clin Memory Res Unit, Dept Clin Sci, Lund, Sweden
Visser, PJ:
Maastricht Univ, Sch Mental Hlth & Neurosci, Dept Psychiat & Neuropsychol, Alzheimer Ctr Limburg, Maastricht, Netherlands
Vrije Univ Amsterdam, Dept Neurol, Alzheimer Ctr Amsterdam, Amsterdam Univ Med Ctr UMC, Amsterdam, Netherlands
Karolinska Inst, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden
Alcolea D.:
Memory Unit, Neurology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden
Department of Neurodegenerative Disease, University College London (UCL), Queen Square Institute of Neurology, Queen Square, London, United Kingdom
UK Dementia Research Institute, London, United Kingdom
Neuropsychiatric Epidemiology Unit, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
Hong Kong Center for Neurodegenerative Diseases, Hong Kong, Hong Kong
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