The DOI matches its Crossref record; 159 of the 159 references it cites were found in a registry or an index.
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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“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]
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“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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(1978) · UA Campus Repository (The University of Arizona) · Cited by 8,010
The hippocampus as a cognitive map
Passingham, R. E. (1979) · Neuroscience · doi:10.1016/0306-4522(79)90015-0 · Cited by 5,128
2016 Alzheimer's disease facts and figures
Alzheimer's Association (2016) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2016.03.001 · Cited by 5,069
Morris water maze: procedures for assessing spatial and related forms of learning and memory
Vorhees, C. V., & Williams, M. T. (2006) · Nature Protocols · doi:10.1038/nprot.2006.116 · Cited by 4,629
Microstructure of a spatial map in the entorhinal cortex
Hafting, T., Fyhn, M., Molden, S., Moser, M.-B., & Moser, E. I. (2005) · Nature · doi:10.1038/nature03721 · Cited by 4,068
Advancing research diagnostic criteria for Alzheimer's disease: the IWG-2 criteria
Dubois, B., Feldman, H. H., Jacova, C., Hampel, H., Molinuevo, J. L., Blennow, K., DeKosky, S. T., Gauthier, S., Selkoe, D., Bateman, R., et al. (2014) · The Lancet Neurology · doi:10.1016/s1474-4422(14)70090-0 · Cited by 3,321
Blennow, K., de Leon, M. J., & Zetterberg, H. (2006) · The Lancet · doi:10.1016/s0140-6736(06)69113-7 · Cited by 3,134
The antibody aducanumab reduces Aβ plaques in Alzheimer’s disease
Sevigny, J., Chiao, P., Bussière, T., Weinreb, P. H., Williams, L., Maier, M., Dunstan, R., Salloway, S., Chen, T., Ling, Y., et al. (2016) · Nature · doi:10.1038/nature19323 · Cited by 3,059
Mental Rotations, a Group Test of Three-Dimensional Spatial Visualization
Vandenberg, S. G., & Kuse, A. R. (1978) · Perceptual and Motor Skills · doi:10.2466/pms.1978.47.2.599 · Cited by 2,620
Nelson, P. T., Alafuzoff, I., Bigio, E. H., Bouras, C., Braak, H., Cairns, N. J., Castellani, R. J., Crain, B. J., Davies, P., Tredici, K. D., et al. (2012) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e31825018f7 · Cited by 2,050
Research works printed but not linked: 1
- Cushman, L. A. & Duffy, C. J. Virtual reality identifies navigational defects in Alzheimer disease and cognitive aging. Nat. Clin. Pract. Neurol. 4, 638–639 (2008).
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Howett, D., Castegnaro, A., Krzywicka, K., Hagman, J., Marchment, D., Henson, R. N., Rio, M., King, J. A., Burgess, N., & Chan, D. (2019) · Brain · doi:10.1093/brain/awz116 · Cited by 243
Coutrot, A., Schmidt, S., Coutrot, L., Pittman, J., Hong, L., Wiener, J. M., Hölscher, C., Dalton, R. C., Hornberger, M., & Spiers, H. J. (2019) · PLOS ONE · doi:10.1371/journal.pone.0213272 · Cited by 177
Self-citationMobile cognition: imaging the human brain in the ‘real world’
Stangl, M., Maoz, S. L., & Suthana, N. (2023) · Nature reviews. Neuroscience · doi:10.1038/s41583-023-00692-y · Cited by 206
Shaw, K., Bell, L., Boyd, K., Grijseels, D. M., Clarke, D., Bonnar, O., Crombag, H. S., & Hall, C. N. (2021) · Nature Communications · doi:10.1038/s41467-021-23508-y · Cited by 198
Toward personalized cognitive diagnostics of at-genetic-risk Alzheimer’s disease
Coughlan, G., Coutrot, A., Khondoker, M. R., Minihane, A. M., Spiers, H. J., & Hornberger, M. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1901600116 · Cited by 191
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Metadata
- 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
- 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
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Social Sciences › Psychology › Experimental and Cognitive Psychology › 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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