Age-specific and sex-specific prevalence of cerebral β-amyloidosis, tauopathy, and neurodegeneration in cognitively unimpaired individuals aged 50–95 years: a cross-sectional study

Abstract

SummaryBackgroundA new descriptive classification scheme for biomarkers used in Alzheimer's and cognitive aging research, labeled ATN, was recently proposed. One implementation of this ATN construct dichotomizes biomarkers of amyloid, tau, and neurodegeneration/neuronal injury as normal or abnormal resulting in 2 × 2× 2=8 possible biomarker profiles. We determined the clinical characteristics and prevalence of each ATN group among clinically normal individuals aged 50 and older from a population based cohort.MethodsAll individuals in this study were participants in the Mayo Clinic Study of Aging, a population-based study of cognitive aging. Potential participants were randomly selected from the Olmsted County, Minnesota population by age- and sex-stratification and invited to participate in cognitive evaluations and undergo multimodality imaging. To be eligible for inclusion in this study, participants must have been judged clinically to have no cognitive impairment and have undergone multi-modality imaging. Imaging studies were obtained from October 11, 2006 to October 5, 2016. All participants were classified as having normal (A−) or abnormal (A+) amyloid using amyloid PET, normal (T−) or abnormal (T+) tau using tau PET, and normal (−) or abnormal (N+) neurodegeneration/neuronal injury using cortical thickness. The cut points used were SUVR 1·42 (centiloid 19) for amyloid PET, 1·23 SUVR for tau PET, and 2·67 mm for MRI cortical thickness. Age- and sex- specific prevalences of the eight ATN biomarker groups were determined using 435 individuals with amyloid PET, tau PET, and MR imaging and 1113 additional clinically normal individuals who underwent amyloid PET and MR imaging, but not tau PET imaging.FindingsThere were 165 A−T−N-, 35 A−T+N-, 63 A−T−N+, 19 A−T+N+, 44 A+T−N−, 25 A+T+N−, 35 A+T−N+, and 49 A+T+N+ individuals. Age differed by ATN group (p<0 001) ranging from a median age of 57 in the A−T−N-−and A−T+N− groups to 80 in the A+T−N+ and A+T+N+ groups. The frequency of APOE ε4 carriers differed by ATN group (p=0·04) with ε4 carriers roughly twice as frequent in A+ versus A−. White matter hyperintensity volume (p<0·0001), and cognitive performance (p<0·0001) also differed by ATN group. Tau PET and neurodegeneration biomarkers were discordant in the majority of individuals who would be labeled stage 2/3 preclinical AD (86% at age 65 and 51% at age 80) or suspected non-Alzheimer's pathophysiology (SNAP) (92% at age 65 and 78% at age 80). From age 50, A−T−N− prevalence declines while A+T+N+ and A−T+N+ increase continuously with age. In both men and women, A−T−N− is the most prevalent group until their late 70s. After about age 80, A+T+N+ is the most prevalent group until their late 70s. After about age 80, A+T+N+ is the most prevalent group. The remaining ATN groups reach individual peaks in the 60–90 age range and then decline in prevalence. By age 85 over 90% of men and women have one or more biomarker abnormalities.InterpretationBiomarkers of fibrillar tau deposition can be included with those of Aβ and neur...

Cognitive and neuroimaging features and brain β-amyloidosis in individuals at risk of Alzheimer's disease (INSIGHT-preAD): a longitudinal observational study

“…The follow-up is still on-going and the number of progressors might increase during further analyses according to a recent estimate of prevalence 59 . However, the number is low and may result from a possible selection bias.…”

Cortical microstructure in young onset Alzheimer's disease using neurite orientation dispersion and density imaging

“…Five of the ROIs were chosen on the basis of being early sites of neuropathological change in AD. These included four regions that comprise the Mayo Clinic cortical signature of AD (entorhinal cortex, inferior temporal gyrus, middle temporal gyrus, and fusiform gyrus) (Jack et al, ; Schwarz et al, ), all of which have been implicated to undergo grey matter atrophy at a relatively early stage of AD (Braak and Braak, ; Dickerson et al, ; Jack et al, ; Petersen et al, ; Weston et al, ) and the precuneus, which has been reported to undergo more pronounced atrophy in YOAD patients (Ishii et al, ; Karas et al, ; Möller et al, ). To investigate if cortical NODDI metrics are potentially a more sensitive marker of AD pathology than cortical macrostructural metrics, the precentral gyrus (primary motor cortex) was included as a ROI.…”

Prevalence and correlates of dementia and mild cognitive impairment classified with different versions of the modified Telephone Interview for Cognitive Status (TICS‐m)

“…An objective hearing test and an assessment of motivation could be useful additions to the interview. Our results are generalizable only to adults in their 70s, which is nonetheless an important period from the point of brain aging …”