A Multi-Dimensional Comparison of Alzheimer's Disease Neurodegenerative Biomarkers.

BACKGROUND: In the 2018 AT(N) framework, neurodegenerative (N) biomarkers plays an essential role in the research and staging of Alzheimer's disease (AD); however, the different choice of N may result in discordances. OBJECTIVE: We aimed to compare different potential N biomarkers. METHODS: We examined these N biomarkers among 1,238 participants from Alzheimer's Disease Neuroimaging Initiative (ADNI) in their 1) diagnostic utility, 2) cross-sectional and longitudinal correlations between different N biomarkers and clinical variables, and 3) the conversion risk of different N profiles. RESULTS: Six neurodegenerative biomarkers changed significantly from preclinical AD, through prodromal AD to AD dementia stage, thus they were chosen as the candidate N biomarkers: hippocampal volume (HV), 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET), cerebrospinal fluid (CSF), total tau (T-tau), plasma neurofilament light chain (NFL), CSF NFL, and CSF neurogranin (Ng). Results indicated that FDG-PET not only had the greatest diagnostic utility in differentiating AD from controls (area under the curve: FDG-PET, 0.922), but also had the strongest association with cognitive scores. Furthermore, FDG-PET positive group showed the fastest memory decline (hazard ratio: FDG-PET, 3.45), which was also true even in the presence of amyloid-ß pathology. Moreover, we observed great discordances between three valuable N biomarkers (FDG-PET, HV, and T-tau). CONCLUSION: These results underline the importance of using FDG-PET as N in terms of cognitive decline and AD conversion, followed by HV, and could be a great complement to the AT(N) framework.

APOE genotype and neuroimaging markers of Alzheimer's disease: systematic review and meta-analysis.

OBJECTIVE: We aimed to examine the association of apolipoprotein E (APOE) ɛ4 genotype with neuroimaging markers of Alzheimer's disease: hippocampal volume, brain amyloid deposition and cerebral metabolism. METHODS: We performed a systematic review and meta-analysis of 14 cross-sectional studies identified in Pubmed from 1996 to 2014 (n=1628). The pooled standard mean difference (SMD) was used to estimate the association between APOE and hippocampal volume and amyloid deposition. Meta-analysis was performed using effect size signed differential mapping using coordinates extracted from clusters with statistically significant difference in cerebral metabolic rate for glucose between APOE ɛ4+ and ɛ4- groups. RESULTS: APOE ɛ4 carrier status was associated with atrophic hippocampal volume (pooled SMD: -0.47; 95% CI -0.82 to -0.13; p=0.007) and increased cerebral amyloid positron emission tomography tracer (pooled SMD: 0.62, 95% CI 0.27 to 0.98, p=0.0006). APOE ɛ4 was also associated with decreased cerebral metabolism, especially in right middle frontal gyrus. CONCLUSIONS: APOE ɛ4 was associated with atrophic hippocampal volume in MRI markers, increased cerebral amyloid deposition and cerebral hypometabolism. Theses associations may indicate the potential role of the APOE gene in the pathophysiology of Alzheimer's disease.