80 Chapter 4 ABSTRACT Background and Objectives Multiple biomarkers have been suggested to measure neurodegeneration (N) in the AT(N) framework, leading to inconsistencies between studies. We investigated the association of five N biomarkers with clinical progression and cognitive decline in individuals with subjective cognitive decline (SCD). Methods We included individuals with SCD from the Amsterdam Dementia Cohort and SCIENCe project, a longitudinal cohort study (follow-up 4±3y). We used the following N biomarkers: CSF total (t)-tau, medial temporal atrophy visual rating on MRI, hippocampal volume (HV), serum neurofilament light (NfL) and serum glial fibrillary acidic protein (GFAP). We determined correlations between biomarkers. We assessed associations between N biomarkers and clinical progression to mild cognitive impairment or dementia (Cox regression), and MMSE over time (linear mixed models). Models included age and sex, CSF β-amyloid (Aβ) (A), and CSF p-tau (T) as covariates, in addition to the N biomarker. Results We included 401 individuals (61±9y, 42%F, MMSE28±2, vascular comorbidities 8-19%). N biomarkers were modestly to moderately correlated (range r -0.28 – 0.58). Serum NfL and GFAP correlated most strongly (r 0.58, p<0.01). T-tau was strongly correlated with p-tau (r 0.89, p<0.01), although these biomarkers supposedly represent separate biomarker groups. All N biomarkers individually predicted clinical progression, but only HV, NfL and GFAP added predictive value beyond Aβ and p-tau (HR 1.52 (95%CI 1.11-2.09); 1.51 (1.05-2.17); 1.50 (1.04-2.15)). T-tau, HV and GFAP individually predicted MMSE slope (range Aβ -0.17 – -0.11, p<0.05), but only HV remained associated beyond Aβ and p-tau (Aβ -0.13 (SE 0.04), p<0.05). Discussion In cognitively unimpaired elderly, correlations between different N biomarkers were only moderate, indicating they reflect different aspects of neurodegeneration and should not be used interchangeably. T-tau was strongly associated with p-tau (T), which makes it less desirable to use as measure for N. HV, NfL and GFAP predicted clinical progression beyond A and T. Our results do not allow to choose one most suitable biomarker for N, but illustrate the added prognostic value of N beyond A and T.
RkJQdWJsaXNoZXIy MjY0ODMw