Spatial navigation deficits — overlooked cognitive marker for preclinical Alzheimer disease?
Open accessAbstract
Detection of incipient Alzheimer disease (AD) pathophysiology is critical to identify preclinical individuals and target potentially disease-modifying therapies towards them. Current neuroimaging and biomarker research is strongly focused in this direction, with the aim of establishing AD fingerprints to identify individuals at high risk of developing this disease. By contrast, cognitive fingerprints for incipient AD are virtually non-existent as diagnostics and outcomes measures are still focused on episodic memory deficits as the gold standard for AD, despite their low sensitivity and specificity for identifying at-risk individuals. This Review highlights a novel feature of cognitive evaluation for incipient AD by focusing on spatial navigation and orientation deficits, which are increasingly shown to be present in at-risk individuals. Importantly, the navigation system in the brain overlaps substantially with the regions affected by AD in both animal models and humans. Notably, spatial navigation has fewer verbal, cultural and educational biases than current cognitive tests and could enable a more uniform, global approach towards cognitive fingerprints of AD and better cognitive treatment outcome measures in future multicentre trials. The current Review appraises the available evidence for spatial navigation and/or orientation deficits in preclinical, prodromal and confirmed AD and identifies research gaps and future research priorities.
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This cellular pathology explains the early cognitive symptoms of AD, such as memory impairment and spatial disorientation.
“However, this cellular pathology explains the early cognitive symptoms of AD, such as memory impairment and spatial disorientation [11].”
From Abnormal accumulation of extracellular vesicles in hippocampal dystrophic axons and regulation by the primary cilia in Alzheimer's disease (2023) · cites this paper as [11]
In “Neuropathology over the lifetime,” the review says neuronal loss is believed to underlie symptoms including forgetfulness and disorientation. The Introduction also describes spatial disorientation in early AD. The claim presents that proposed causal explanation as established fact, whereas the review qualifies it as a belief. (LLM, conf=0.86)
Experimental — accuracy not yet measuredSpatial navigation patterns are affected by dementia and are considered as one of the earliest symptoms.
“Spatial navigation patterns are affected by dementia and are considered as one of the earliest symptoms [112].”
From Human-centred artificial intelligence for mobile health sensing: challenges and opportunities (2023) · cites this paper as [112]
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- Authors
- Coughlan, G., Laczó, J., Hort, J., Minihane, A.-M., & Hornberger, M.
- Affiliations
- University of East Anglia (GB)
- Charles University (CZ)
- Corresponding author
- Hornberger, Michael
- Venue
- Nature Reviews Neurology
- Published
- 2018-07-06
- Volume
- 14
- Issue
- 8
- Pages
- 496-506
- ISSN
- 1759-4758 (ISSN-L)
- 1759-4766
- OpenAlex
- W2810517026
- Cited by
- 500
- References
- 159
- Citations by year
- 2026: 63 · 2025: 73 · 2024: 77 · 2023: 90 · 2022: 66 · 2021: 57 · 2020: 38 · 2019: 32 · 2018: 3 · 2017: 1
- FWCI
- 5.02
- Type
- journal article
- Language
- en
- Open access
- green
- ueaeprints.uea.ac.uk
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Reviews Neurology (publishedVersion)
- PubMed (publishedVersion)
- UEA Digital Repository (University of East Anglia) (acceptedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Physical Sciences › Engineering › Automotive Engineering › Spatial Cognition and Navigation
- Keywords
- preclinical Alzheimer's disease, spatial orientation, prodromal Alzheimer's disease, episodic memory, cognitive outcome measures, Alzheimer's disease biomarkers
- MeSH terms
- Alzheimer Disease, Animals, Humans, Biomarkers, Prodromal Symptoms, Spatial Navigation
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