Lower Locus Coeruleus Integrity Signals Elevated Entorhinal Tau and Clinical Progression in Asymptomatic Older Individuals
Year: 2024
Type: article
Study design: Observational Study
Abstract: OBJECTIVE: Elevated entorhinal cortex (EC) tau in low beta-amyloid individuals can predict accumulation of pathology and cognitive decline. We compared the accuracy of magnetic resonance imaging (MRI)-derived locus coeruleus integrity, neocortical beta-amyloid burden by positron emission tomography (PET), and hippocampal volume in identifying elevated entorhinal tau signal in asymptomatic individuals who are considered beta-amyloid PET-negative. METHODS: We included 188 asymptomatic individuals (70.78 ± 11.51 years, 58% female) who underwent 3T-MRI of the locus coeruleus, Pittsburgh compound-B (PiB), and Flortaucipir (FTP) PET. Associations between elevated EC tau and neocortical PiB, hippocampal volume, or locus coeruleus integrity were evaluated and compared using logistic regression and receiver operating characteristic analyses in the PiB- sample with a clinical dementia rating (CDR) of 0. Associations with clinical progression (CDR-sum-of-boxes) over a time span of 6 years were evaluated with Cox proportional hazard models. RESULTS: We identified 26 (21%) individuals with high EC FTP in the CDR = 0/PiB- sample. Locus coeruleus integrity was a significantly more sensitive and specific predictor of elevated EC FTP (area under the curve [AUC] = 85%) compared with PiB (AUC = 77%) or hippocampal volume (AUC = 76%). Based on the Youden-index, locus coeruleus integrity obtained a sensitivity of 77% and 85% specificity. Using the resulting locus coeruleus Youden cut-off, lower locus coeruleus integrity was associated with a two-fold increase in clinical progression, including mild cognitive impairment. INTERPRETATION: Locus coeruleus integrity has promise as a low-cost, non-invasive screening instrument to detect early cortical tau deposition and associated clinical progression in asymptomatic, low beta-amyloid individuals. ANN NEUROL 2024;96:650-661.
Source: Annals of Neurology
DOI: 10.1002/ana.27022
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,300
Funders: Centre d'Imagerie BioMédicale, National Institutes of Health, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, National Institute on Aging, NIH Office of the Director, National Institute of Biomedical Imaging and Bioengineering, National Center for Research Resources
Awards: G1215728109, G1220546045, G1360098495, G2227408383, Elevated locus coeruleus metabolism as mechanism driving Alzheimer's disease pathology, G3549079774, G393103480, G4170966788, G4507898398, G4922088058, Inference by interference: Task-dependent pupil responses as an early detection method for Alzheimer's disease related brainstem functional change, Tracking the origin of tau pathology, Disentangling the contribution of tau to aging and AD, Computeserver Structural &Functional Image Analysis, 3T MRI for Clinical and Translational Imaging, Gamma counter and continuous blood sampler for quantitative PET imaging, G653110949, Center for Molecular Imaging Technology & Translation (CMITT), A Siemens MAGNETOTOM Trio 3 Tesla MRI System, Center for Functional Imaging Technologies, A Storage Area Network for Structural and Functional Image Analysis, Locus coeruleus network architecture of Alzheimer's disease vulnerability, Impact of Amyloid and Tau on the Aging Brain: The Harvard Aging Brain Study, Contribution of locus coeruleus activity patterns on tau deposition in Alzheimer's disease, The wandering nerve: gateway to boost Alzheimer's disease related cognitive performance, Silicon Graphics Prism Extreme 128P/1TB
OpenAlex ID: W4400656747