Spatial navigation is a skill of determining and maintaining a trajectory from one place to another. Mild progressive decline of spatial navigation develops gradually during the course of physiological ageing. Nevertheless, severe spatial navigation deficit can be the first sign of incipient Alzheimer's disease (AD), occurring in the stage of mild cognitive impairment (MCI), preceding the development of a full blown dementia. Patients with amnestic MCI, especially those with the hippocampal type of amnestic syndrome, are at very high risk of AD. These patients present with the same pattern of spatial navigation impairment as do the patients with mild AD. Spatial navigation testing of elderly as well as computer tests developed for routine clinical use thus represents a possibility for further investigation of this cognitive domain, but most of all, an opportunity for making early diagnosis of AD.

Department of Neurology Memory Disorders Clinic 2nd Faculty of Medicine Charles University Prague and University Hospital Motol Prague 5 Czech Republic

See more in PubMed

Albert M. S., DeKosky S. T., Dickson D., Dubois B., Feldman H. H., Fox N. C., Gamst A., Holtzman D. M., Jagust W. J., Petersen R. C., Snyder P. J., Carrillo M. C., Thies B., Phelps C. H. (2011). The diagnosis of mild cognitive impairment due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 7, 270–279 10.1016/j.jalz.2011.03.008 PubMed DOI PMC

Astur R. S., Taylor L. B., Mamelak A. N., Philpott L., Sutherland R. J. (2002). Humans with hippocampus damage display severe spatial memory impairments in a virtual Morris water task. Behav. Brain Res. 132, 77–84 10.1016/S0166-4328(01)00399-0 PubMed DOI

Barrash J. (1994). Age-related decline in route learning ability. Dev. Neuropsychol. 10, 189–201

Baudic S., Barba G. D., Thibaudet M. C., Smagghe A., Remy P., Traykov L. (2006). Executive function deficits in early Alzheimer's disease and their relations with episodic memory. Arch. Clin. Neuropsychol. 21, 15–21 10.1016/j.acn.2005.07.002 PubMed DOI

Begega A., Cienfuegos S., Rubio S., Santín J. L., Miranda R., Arias J. L. (2001). Effects of ageing on allocentric and egocentric spatial strategies in the Wistar rat. Behav. Processes 53, 75–85 10.1016/S0376-6357(00)00150-9 PubMed DOI

Bellassen V., Iglói K., de Souza L. C., Dubois B., Rondi-Reig L. (2012). Temporal order memory assessed during spatiotemporal navigation as a behavioral cognitive marker for differential Alzheimer's disease diagnosis. J. Neurosci. 32, 1942–1952 10.1523/JNEUROSCI.4556-11.2012 PubMed DOI PMC

Braak H., Braak E. (1991). Neuropathological staging of Alzheimer-related changes. Acta Neuropathol. 82, 239–259 PubMed

Brun V. H., Leutgeb S., Wu H. Q., Schwarcz R., Witter M. P., Moser E. I., Moser M. B. (2008). Impaired spatial representation in CA1 after lesion of direct input from entorhinal cortex. Neuron 57, 290–302 10.1016/j.neuron.2007.11.034 PubMed DOI

Burns P. C. (1999). Navigation and the mobility of older drivers. J. Gerontol. B Psychol. Sci. Soc. Sci. 54, 49–55 PubMed

Cabeza R., Grady C. L., Nyberg L., McIntosh A. R., Tulving E., Kapur S., Jennings J. M., Houle S., Craik F. I. (1997). Age-related differences in neural activity during memory encoding and retrieval: a positron emission tomography study. J. Neurosci. 17, 391–400 10.1001/archneur.1989.00520400045018 PubMed DOI PMC

Carlesimo G. A., Perri R., Caltagirone C. (2011). Category cued recall following controlled encoding as a neuropsychological tool in the diagnosis of Alzheimer's disease: a review of the evidence. Neuropsychol. Rev. 21, 54–65 10.1007/s11065-010-9153-7 PubMed DOI

Chételat G., Fouquet M., Kalpouzos G., Denghien I., De la Sayette V., Viader F., Mézenge F., Landeau B., Baron J. C., Eustache F., Desgranges B. (2008). Three-dimensional surface mapping of hippocampal atrophy progression from MCI to AD and over normal aging as assessed using voxel-based morphometry. Neuropsychologia 46, 1721–1731 10.1016/j.neuropsychologia.2007.11.037 PubMed DOI

Cushman L. A., Stein K., Duffy C. J. (2008). Detecting navigational deficits in cognitive aging and Alzheimer disease using virtual reality. Neurology 71, 888–895 10.1212/01.wnl.0000326262.67613.fe PubMed DOI PMC

deIpolyi A. R., Rankin K. P., Mucke L., Miller B. L., Gorno-Tempini M. L. (2007). Spatial cognition and the human navigation network in AD and MCI. Neurology 69, 986–997 10.1212/01.wnl.0000271376.19515.c6 PubMed DOI

de Jager C. A., Honey T. E., Birks J., Wilcock G. K. (2010). Retrospective evaluation of revised criteria for the diagnosis of Alzheimer's disease using a cohort with post-mortem diagnosis. Int. J. Geriatr. Psychiatry 25, 988–997 10.1002/gps.2448 PubMed DOI

Desikan R. S., Sabuncu M. R., Schmansky N. J., Reuter M., Cabral H. J., Hess C. P., Weiner M. W., Biffi A., Anderson C. D., Rosand J., Salat D. H., Kemper T. L., Dale A. M., Sperling R. A., Fischl B. (2010). Alzheimer's disease neuroimaging initiative. Selective disruption of the cerebral neocortex in Alzheimer's disease. PLoS ONE 5:e12853 10.1371/journal.pone.0012853 PubMed DOI PMC

Devanand D. P., Bansal R., Liu J., Hao X., Pradhaban G., Peterson B. S. (2012). MRI hippocampal and entorhinal cortex mapping in predicting conversion to Alzheimer's disease. Neuroimage 60, 1622–1629 10.1016/j.neuroimage.2012.01.075 PubMed DOI PMC

Driscoll I., Hamilton D. A., Petropoulos H., Yeo R. A., Brooks W. M., Baumgartner R. N., Sutherland R. J. (2003). The aging hippocampus: cognitive, biochemical and structural findings. Cereb. Cortex 13, 1344–1351 10.1093/cercor/bhg081 PubMed DOI

Dubois B. (2000). ‘Prodromal Alzheimer's disease’: a more useful concept than mild cognitive impairment? Curr. Opin. Neurol. 13, 367–369 PubMed

Dubois B., Albert M. L. (2004). Amnestic MCI or prodromal Alzheimer's disease? Lancet Neurol. 3, 246–248 10.1016/S1474-4422(04)00710-0 PubMed DOI

Dubois B., Feldman H. H., Jacova C., Dekosky S. T., Barberger-Gateau P., Cummings J., Delacourte A., Galasko D., Gauthier S., Jicha G., Meguro K., O'brien J., Pasquier F., Robert P., Rossor M., Salloway S., Stern Y., Visser P. J., Scheltens P. (2007). Research criteria for the diagnosis of Alzheimer's disease: revising the NINCDS-ADRDA criteria. Lancet Neurol. 6, 734–746 10.1016/S1474-4422(07)70178-3 PubMed DOI

Frisoni G. B., Ganzola R., Canu E., Rüb U., Pizzini F. B., Alessandrini F., Zoccatelli G., Beltramello A., Caltagirone C., Thompson P. M. (2008). Mapping local hippocampal changes in Alzheimer's disease and normal ageing with MRI at 3 Tesla. Brain 131, 3266–3276 10.1093/brain/awn280 PubMed DOI

Gallistel C. R. (1990). The Organization of Learning. Cambridge, MA: MIT Press; 10.1016/j.beproc.2006.10.007 DOI

Grady C. L., McIntosh A. R., Rajah M. N., Beig S., Craik F. I. (1999). The effects of age on the neural correlates of episodic encoding. Cereb. Cortex 9, 805–814 10.1093/cercor/9.8.805 PubMed DOI

Grober E., Buschke H., Crystal H., Bang S., Dresner R. (1988). Screening for dementia by memory testing. Neurology 38, 900–903 PubMed

Head D., Isom M. (2010). Age effects on wayfinding and route learning skills. Behav. Brain Res. 209, 49–58 10.1016/j.bbr.2010.01.012 PubMed DOI

Henderson V. W., Mack W., Williams B. W. (1989). Spatial disorientation in Alzheimer's disease. Arch. Neurol. 46, 391–394 PubMed

Holdstock J. S., Mayes A. R., Cezayirli E., Isaac C. L., Aggleton J. P., Roberts N. (2000). A comparison of egocentric and allocentric spatial memory in a patient with selective hippocampal damage. Neuropsychologia 38, 410–425 10.1016/S0028-3932(99)00099-8 PubMed DOI

Hort J., Laczó J., Vyhnálek M., Bojar M., Bures J., Vlcek K. (2007). Spatial navigation deficit in amnestic mild cognitive impairment. Proc. Natl. Acad. Sci. U.S.A. 104, 4042–4047 10.1073/pnas.0611314104 PubMed DOI PMC

Hulstaert F., Blennow K., Ivanoiu A., Schoonderwaldt H. C., Riemenschneider M., De Deyn P. P., Bancher C., Cras P., Wiltfang J., Mehta P. D., Iqbal K., Pottel H., Vanmechelen E., Vanderstichele H. (1999). Improved discrimination of AD patients using beta-amyloid(1-42) and tau levels in CSF. Neurology 52, 1555–1562 PubMed

Iaria G., Palermo L., Committeri G., Barton J. (2009). Age differences in the formation and use of cognitive maps. Behav. Brain Res. 196, 187–191 10.1016/j.bbr.2008.08.040 PubMed DOI

Ingram D. K. (1988). Complex maze learning in rodents as a model of age-related memory impairment. Neurobiol. Aging 9, 475–485 PubMed

Jack C. R., Jr., Petersen R. C., Xu Y. C., O'Brien P. C., Smith G. E., Ivnik R. J., Tangalos E. G., Kokmen E. (1998). Rate of medial temporal lobe atrophy in typical aging and Alzheimer's disease. Neurology 51, 993–999 PubMed PMC

Jack C. R., Jr., Petersen R. C., Xu Y. C., Waring S. C., O'Brien P. C., Tangalos E. G., Smith G. E., Ivnik R. J., Kokmen E. (1997). Medial temporal atrophy on MRI in normal aging and very mild Alzheimer's disease. Neurology 49, 786–794 PubMed PMC

Kase C. S., Troncoso J. F., Court J. E., Tapia J. F., Mohr J. P. (1977). Global spatial disorientation. Clinico-pathologic correlations. J. Neurol. Sci. 34, 267–278 10.1016/0022-510X(77)90074-0 PubMed DOI

Kavcic V., Fernandez R., Logan D., Duffy C. J. (2006). Neurophysiological and perceptual correlates of navigational impairment in Alzheimer's disease. Brain 129, 736–746 10.1093/brain/awh727 PubMed DOI

Kertesz A., Appell J., Fisman M. (1986). The dissolution of language in Alzheimer's disease. Can. J. Neurol. Sci. 13, 415–418 PubMed

Klein D. A., Steinberg M., Galik E., Steele C., Sheppard J. M., Warren A., Rosenblatt A., Lyketsos C. G. (1999). Wandering behaviour in community-residing persons with dementia. Int. J. Geriatr. Psychiatry 14, 272–279 PubMed

Laczó J., Andel R., Vlèek K., Macoška V., Vyhnálek M., Tolar M., Bojar M. (2011). Spatial navigation and APOE in amnestic mild cognitive impairment. Neurodegener. Dis. 8, 169–177 10.1159/000321581 PubMed DOI

Laczó J., Andel R., Vyhnalek M., Vlcek K., Magerova H., Varjassyova A., Nedelska Z., Gazova I., Bojar M., Sheardova K., Hort J. (2012). From morris water maze to computer tests in the prediction of Alzheimer's disease. Neurodegener. Dis. 10, 153–157 10.1159/000333121 PubMed DOI

Laczó J., Vlček K., Vyhnálek M., Vajnerová O., Ort M., Holmerová I., Tolar M., Anděl R., Bojar M., Hort J. (2009). Spatial navigation testing discriminates two types of amnestic mild cognitive imairment. Behav. Brain Res. 202, 252–259 10.1016/j.bbr.2009.03.041 PubMed DOI

Levine D. N., Warach J., Farah M. (1985). Two visual systems in mental imagery: dissociation of “what” and “where” in imagery disorders due to bilateral posterior cerebral lesions. Neurology 35, 1010–1018 PubMed

Lipman P. D. (1991). Age and exposure differences in acquisition of route information. Psychol. Aging 6, 128–133 PubMed

Maguire E. A., Burgess N., Donnett J. G., Frackowiak R. S., Frith C. D., O'Keefe J. (1998). Knowing where and getting there: a human navigation network. Science 280, 921–924 10.1126/science.280.5365.921 PubMed DOI

Mapstone M., Steffenella T. M., Duffy C. J. (2003). A visuospatial variant of mild cognitive impairment: getting lost between aging and AD. Neurology 60, 802–808 PubMed

McKhann G. M., Knopman D. S., Chertkow H., Hyman B. T., Jack C. R., Jr., Kawas C. H., Klunk W. E., Koroshetz W. J., Manly J. J., Mayeux R., Mohs R. C., Morris J. C., Rossor M. N., Scheltens P., Carrillo M. C., Thies B., Weintraub S., Phelps C. H. (2011). The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 7, 263–269 10.1016/j.jalz.2011.03.005 PubMed DOI PMC

McLay R. N., Freeman S. M., Harlan R. E., Kastin A. J., Zadina J. E. (1999). Tests used to assess the cognitive abilities of aged rats: their relation to each other and to hippocampal morphology and neurotrophin expression. Gerontology 45, 143–155 PubMed

Modrego P. J., Fayed N., Sarasa M. (2011). Magnetic resonance spectroscopy in the prediction of early conversion from amnestic mild cognitive impairment to dementia: a prospective cohort study. BMJ Open 1, e000007 10.1136/bmjopen-2010-000007 PubMed DOI PMC

Moffat S. D., Kennedy K. M., Rodrigue K. M., Raz N. (2006). Extrahippocampal contributions to age differences in human spatial navigation. Cereb. Cortex 17, 1274–1282 10.1093/cercor/bhl036 PubMed DOI

Moffat S. D., Resnick S. M. (2002). Effects of age on virtual environment place navigation and allocentric cognitive mapping. Behav. Neurosci. 116, 851–859 PubMed

Monacelli A. M., Cushman L. A., Kavcic V., Duffy C. J. (2003). Spatial disorientation in Alzheimer's disease: the remembrance of things passed. Neurology 61, 1491–1497 PubMed

Morris G. M. (1981). Spatial localization does not require the presence of local cues. Learn. Motiv. 12, 239–260

Morris R. G., Garrud P., Rawlins J. N., O'Keefe J. (1982). Place navigation impaired in rats with hippocampal lesions. Nature 297, 681–683 PubMed

Morris J. C., Storandt M., Miller J. P., McKeel D. W., Price J. L., Rubin E. H., Berg L. (2001). Mild cognitive impairment represents early-stage Alzheimer disease. Arch. Neurol. 58, 397–405 PubMed

Mountcastle V. B., Lynch J. C., Georgopoulos A., Sakata H., Acuna C. (1975). Posterior parietal association cortex of the monkey: command functions for operations within extrapersonal space. J. Neurophysiol. 38, 871–908 PubMed

Mueller S. G., Weiner M. W. (2009). Selective effect of age, Apo e4, and Alzheimer's disease on hippocampal subfields. Hippocampus 19, 558–564 10.1002/hipo.20614 PubMed DOI PMC

Nedelska Z., Andel R., Laczó J., Vlcek K., Horinek D., Lisy J., Sheardova K., Bures J., Hort J. (2012). Spatial navigation impairment is proportional to right hippocampal volume. Proc. Natl. Acad. Sci. U.S.A. 109, 2590–2594 10.1073/pnas.1121588109 PubMed DOI PMC

Newman M. C., Kaszniak A. W. (2000). Spatial memory and aging: performance on a human analog of the Morris water maze task. Aging Neuropsychol. Cogn. 7, 86–93

O'Keefe J., Dostrovsky J. (1971). The hippocampus as a spatial map. Preliminary evidence from unit activity in the freely-moving rat. Brain Res. 34, 171–175 10.1016/0006-8993(71)90358-1 PubMed DOI

O'Keefe J., Nadel L. (1978). The Hippocampus as A Cognitive Map. Oxford: Clarendon

Pai M. C., Jacobs W. J. (2004). Topographical disorientation in community-residing patients with Alzheimer's disease. Int. J. Geriatr. Psychiatry 19, 250–255 PubMed

Park D. C. (2000). “Basic mechanisms accounting for age-related decline in cognitive functions,” in Cognitive Ageing. A Primer, eds Park D. C., Schwarz N. (Philadelphia, PA: Psychology; ), 3–21

Petersen R. C., Doody R., Kurz A., Mohs R. C., Morris J. C., Rabins P. V., Ritchie K., Rossor M., Thal L., Winblad B. (2001). Current concepts in mild cognitive impairment. Arch. Neurol. 58, 1985–1992 PubMed

Petersen R. C., Morris J. C. (2003). “Clinical features,” in Mild Cognitive Impairment: Aging to Alzheimer's Disease, ed. Petersen R. C. (New York, NY: Oxford University Press, Inc.), 15–40

Petersen R. C., Smith G. E., Waring S. C., Ivnik R. J., Tangalos E. G., Kokmen E. (1999). Mild cognitive impairment: clinical characterization and outcome. Arch. Neurol. 56, 303–308 PubMed

Resnick S. M., Pham D. L., Kraut M. A., Zonderman A. B., Davatzikos C. (2003). Longitudinal magnetic resonance imaging studies of older adults: a shrinking brain. J. Neurosci. 23, 3295–3301 PubMed PMC

Resnick S. M., Sojkova J., Zhou Y., An Y., Ye W., Holt D. P., Dannals R. F., Mathis C. A., Klunk W. E., Ferrucci L., Kraut M. A., Wong D. F. (2010). Longitudinal cognitive decline is associated with fibrillar amyloid-beta measured by [11C]PiB. Neurology 74, 807–815 10.1212/WNL.0b013e3181d3e3e9 PubMed DOI PMC

Rodgers M. K., Sindone J. A., III., Moffat S. D. (2012). Effects of age on navigation strategy. Neurobiol. Aging 33, 202.e15–22 10.1016/j.neurobiolaging.2010.07.021 PubMed DOI PMC

Sarazin M., Berr C., De Rotrou J., Fabrigoule C., Pasquier F., Legrain S., Michel B., Puel M., Volteau M., Touchon J., Verny M., Dubois B. (2007). Amnestic syndrome of the medial temporal type identifies prodromal AD: a longitudinal study. Neurology 69, 1859–1867 10.1212/01.wnl.0000279336.36610.f7 PubMed DOI

Sarazin M., Chauviré V., Gerardin E., Colliot O., Kinkingnéhun S., de Souza L. C., Hugonot-Diener L., Garnero L., Lehéricy S., Chupin M., Dubois B. (2010). The amnestic syndrome of hippocampal type in Alzheimer's disease: an MRI study. J. Alzheimers Dis. 22, 285–294 10.3233/JAD-2010-091150 PubMed DOI

Scahill R. I., Schott J. M., Stevens J. M., Rossor M. N., Fox N. C. (2002). Mapping the evolution of regional atrophy in Alzheimer's disease: unbiased analysis of fluid-registered serial MRI. Proc. Natl. Acad. Sci. U.S.A. 99, 4703–4707 10.1073/pnas.052587399 PubMed DOI PMC

Shaw L., Vanderstichele H., Knapik-Czajka M., Clark C., Aisen P., Petersen R. C., Blennow K., Soares H., Simon A., Lewczuk P., Dean R., Siemers E., Potter W., Lee V. M., Trojanowski J. Q. (2009). Alzheimer's disease neuroimaging initiative. Cerebrospinal fluid biomarker signature in Alzheimer's disease neuroimaging initiative subjects. Ann. Neurol. 65, 403–413 10.1002/ana.21610 PubMed DOI PMC

Small S. A., Perera G. M., DeLaPaz R., Mayeux R., Stern Y. (1999). Differential regional dysfunction of the hippocampal formation among elderly with memory decline and Alzheimer's disease. Ann. Neurol. 45, 466–472 PubMed

Squire L. R. (1992). Memory and the hippocampus: a synthesis from findings with rats, monkeys and humans. Psychol. Rev. 99, 195–231 PubMed

Stark M., Coslett H. B., Saffran E. M. (1996). Impairment of an egocentric map of locations: implications for perception and action. Cogn. Neuropsychol. 13, 481–524

Suthana N. A., Ekstrom A. D., Moshirvaziri S., Knowlton B., Bookheimer S. Y. (2009). Human hippocampal CA1 involvement during allocentric encoding of spatial information. J. Neurosci. 29, 10512–10519 10.1523/JNEUROSCI.0621-09.2009 PubMed DOI PMC

Tierney M. C., Szalai J. P., Snow W. G., Fisher R. H., Nores A., Nadon G., Dunn E., St. George-Hyslop P. H. (1996). Prediction of probable Alzheimer's disease in memory-impaired patients: a prospective longitudinal study. Neurology 46, 661–665 PubMed

Tolman E. C. (1948). Cognitive maps in rats and men. Psychol. Rev. 56, 144–155 PubMed

Visser P. J., Scheltens P., Verhey F. R., Schmand B., Launer L. J., Jolles J., Jonker C. (1999). Medial temporal lobe atrophy and memory dysfunction as predictors for dementia in subjects with mild cognitive impairment. J. Neurol. 246, 477–485 10.1007/s004150050387 PubMed DOI

Vlcek K. (2011). “Spatial navigation impairment in healthy aging and Alzheimer's disease,” in The Clinical Spectrum of Alzheimer's Disease. The Charge toward Comprehensive Diagnostic and Therapeutic Strategies, ed. De La Monte S. (Rijeka, Croatia: Intech; ), 75–100

Weniger G., Ruhleder M., Lange C., Wolf S., Irle E. (2011). Egocentric and allocentric memory as assessed by virtual reality in individuals with amnestic mild cognitive impairment. Neuropsychologia 49, 518–527 10.1016/j.neuropsychologia.2010.12.031 PubMed DOI

Wilkniss S. M., Jones M. G., Korol D. L., Gold P. E., Manning C. A. (1997). Age-related differences in an ecologically based study of route learning. Psychol. Aging 12, 372–375 PubMed

Spatial navigation is associated with subcortical alterations and progression risk in subjective cognitive decline

The McGill Transgenic Rat Model of Alzheimer's Disease Displays Cognitive and Motor Impairments, Changes in Anxiety and Social Behavior, and Altered Circadian Activity

Neural correlates of spatial navigation changes in mild cognitive impairment and Alzheimer's disease

Spatial navigation in young versus older adults