- Alzheimer's disease and Lewy body disease commonly produce spatial navigation impairments; these deficits are less pronounced in frontotemporal dementia and limbic-predominant age-related TDP-43 encephalopathy.
- Basal forebrain degeneration occurs across neurodegenerative diseases, but cholinergic pathway disruption and cholinergic deficits are principally observed in Alzheimer's disease and Lewy body disease.
- Disease-related basal forebrain changes are linked to impaired spatial navigation in humans, underscoring cholinergic mechanisms as targets for understanding and treating navigation deficits.
Trends Neurosci. 2026 Sep 5:S0166-2236(26)00165-7. doi: 10.1016/j.tins.2026.08.005. Online ahead of print.
ABSTRACT
Neurodegenerative diseases such as Alzheimer’s disease (AD) and Lewy body disease (LBD) are frequently associated with spatial navigation impairments. However, these impairments are less pronounced in frontotemporal dementia and limbic-predominant age-related TDP-43 encephalopathy. While basal forebrain degeneration occurs in all of these diseases, disruption of cholinergic pathways and related cholinergic deficits has been primarily observed in AD and LBD, and in both of these conditions, basal forebrain degeneration appears to be associated with spatial navigation deficits. In this review, we discuss current understanding of spatial navigation impairments in neurodegenerative diseases, with a particular focus on disease-related changes in the basal forebrain and their associations with impaired spatial navigation abilities in humans.
PMID:42701059 | DOI:10.1016/j.tins.2026.08.005
Share Evidence Blueprint
Save to Google Notes
Search Google Scholar
Save as PDF
⭐ My Revision List
