For example, for the pathways significantly enriched with top 100 differentially expressed genes of cognitive decline (Fig. 5A), the Thyrotropin releasing hormone (TRH) receptor signaling pathway (FDR = 3.54 × 10–2) has been associated with aging and neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease38. The gene discussed is TRH; the disease is early-onset autosomal dominant Alzheimer disease.