Cognitive decline caused by ageing and neurodegeneration is a considerable healthcare challenge in our rapidly ageing population. This chapter delves into the critical function of RNA transcriptomics in understanding and treating age- and neurodegeneration-related cognitive alterations. We provide a detailed overview of numerous RNA modifications and their regulatory mechanisms, including changes to messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). Specific tRNA changes, including 5-methylcytosine (m5C), queuosine (Q), and pseudouridine (Ψ), have been identified as key participants in neurodegenerative processes. The chapter also looks at the regulatory roles of noncoding RNAs, including microRNAs and long noncoding RNAs, in cognitive function and dysfunction. We address how RNA alterations affect synaptic plasticity and memory formation and their changed patterns in diverse neurodegenerative diseases. We also look at the therapeutic potential of targeting RNA changes and the promising function of epigenetic medicines in cognitive health.