Physical Inactivity is Associated with Parkinson's Disease Mild Cognitive Impairment and Dementia.

The blood-brain barrier (BBB) offers a highly specialized protective boundary for the brain, but severely limits therapeutic delivery, posing major challenges for treating neurological diseases and solid tumors. Focused ultrasound (FUS) has emerged as a powerful tool to noninvasively and transiently disrupt the BBB to enable localized delivery of drugs and gene therapies. More commonly paired with viral vectors like adeno-associated virus (AAV), FUS is now being explored with non-viral vectors such as polymeric and lipid nanoparticles, which offer tunable chemistry, repeat dosing potential, and capability to deliver varying cargos. Upon promising advances, future directions aim to improve safety, target immune modulation, and integrate diagnostic imaging for theranostic potential. Overall, the convergence of FUS and non-viral nanocarrier technologies represents a transformative approach for precise, minimally invasive, and accessible gene delivery to the central nervous system.