Spatial Navigation and APOE in Amnestic Mild Cognitive Impairment

Background: The effect of APOE Ε4 allele (Ε4) on spatial navigation in amnestic mild cognitive impairment (aMCI) is unknown. Objective: Our purpose was to examine the characteristics of spatial navigation impairment in Ε4-positive (Ε4+) and Ε4-negative (Ε4–) aMCI subgroups. Methods: Blood samples were collected to determine the APOE genotype. A total of 34 aMCI patients were stratified into aMCI-Ε4– (n = 23) and aMCI-Ε4+ (n = 11) groups. Control (n = 28) and mild Alzheimer’s disease (AD; n = 16) groups were also used. We used a human analogue of the Morris water maze (enclosed arena 2.9 m in diameter) to examine body-centered (egocentric) and world-centered (allocentric) spatial navigation. Results: The aMCI-Ε4+ group performed poorer on spatial navigation than the aMCI-Ε4– group in both egocentric and allocentric tasks even though these 2 groups did not differ in global cognitive functioning or neuropsychological tests. The aMCI-Ε4+ and mild AD groups performed similarly on all Morris Water Maze tasks and were outperformed by the aMCI-Ε4– group, which also resembled the control group in performance on the egocentric tasks. The aMCI groups showed poor spatial navigation learning regardless of their Ε4 positivity. Conclusion: We found more profound deficits in spatial navigation in aMCI-Ε4+ relative to aMCI-Ε4– patients. The aMCI-Ε4+ group resembled the mild AD group in spatial navigation performance. Although the Ε4 genotype was indicative of spatial navigation performance, it was not indicative of the aMCI patients’ ability to learn the tasks. Spatial navigation testing represents a promising area with respect to identifying individuals at higher risk for AD among the heterogeneous MCI population.

[1]  Jan Bureš,et al.  Allothetic orientation and sequential ordering of places is impaired in early stages of Alzheimer's disease: corresponding results in real space tests and computer tests , 2005, Behavioural Brain Research.

[2]  R. Morris,et al.  Place navigation impaired in rats with hippocampal lesions , 1982, Nature.

[3]  J. Feigenbaum,et al.  Allocentric versus egocentric spatial memory after unilateral temporal lobectomy in humans. , 2004, Neuropsychology.

[4]  Jan Bures,et al.  A battery of tests for quantitative examination of idiothetic and allothetic place navigation modes in humans , 2003, Behavioural Brain Research.

[5]  Richard J. Beninger,et al.  The Hippocampal and Parietal Foundations of Spatial Cognition , 2001 .

[6]  J. Woo,et al.  Apolipoprotein E ε4 allele is not associated with the cognitive impairment in community‐dwelling normal elderly individuals , 2002 .

[7]  J. Lindeboom,et al.  Association between apolipoprotein E ε4 and the rate of cognitive decline in community-dwelling elderly individuals with and without dementia , 1998 .

[8]  David A Wolk,et al.  Apolipoprotein E (APOE) genotype has dissociable effects on memory and attentional–executive network function in Alzheimer’s disease , 2010, Proceedings of the National Academy of Sciences.

[9]  M. Pericak-Vance,et al.  Specificity, sensitivity, and predictive value of apolipoprotein-E genotyping for sporadic Alzheimer's disease , 1996, The Lancet.

[10]  R. Petersen.  Mild cognitive impairment as a diagnostic entity , 2004, Journal of internal medicine.

[11]  D. Selkoe,et al.  In search of γ-secretase: Presenilin at the cutting edge , 2000 .

[12]  M. Folstein,et al.  Clinical diagnosis of Alzheimer's disease: Report of the NINCDS—ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease , 2011, Neurology.

[13]  K. Jeffery,et al.  The Hippocampal and Parietal Foundations of Spatial Cognition , 1999 .

[14]  J. Mortimer,et al.  Is APOE-ε4 a risk factor for cognitive impairment in normal aging? , 2000, Neurology.

[15]  V. Henderson,et al.  Spatial disorientation in Alzheimer's disease. , 1989, Archives of Neurology.

[16]  Raja Parasuraman,et al.  Genetics and visual attention: Selective deficits in healthy adult carriers of the ɛ4 allele of the apolipoprotein E gene , 2000 .

[17]  L. Mucke,et al.  Isoform-specific effects of human apolipoprotein E on brain function revealed in ApoE knockout mice: increased susceptibility of females. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[18]  L. Mucke,et al.  Alzheimer's disease: Apolipoprotein E and cognitive performance , 2000, Nature.

[19]  Lars Bäckman,et al.  Apolipoprotein E and cognitive performance: a meta-analysis. , 2004, Psychology and aging.

[20]  J. O'Keefe,et al.  The hippocampus as a spatial map. Preliminary evidence from unit activity in the freely-moving rat. , 1971, Brain research.

[21]  R. Parasuraman,et al.  Effects of apolipoprotein E genotype on spatial attention, working memory, and their interaction in healthy, middle-aged adults: results From the National Institute of Mental Health's BIOCARD study. , 2005, Neuropsychology.

[22]  L. Mucke,et al.  Spatial cognition and the human navigation network in AD and MCI , 2007, Neurology.

[23]  W. Snow,et al.  A prospective study of the clinical utility of ApoE genotype in the prediction of outcome in patients with memory impairment , 1996, Neurology.

[24]  R. Frackowiak,et al.  Clinical and Neuroimaging Features of Familial Alzheimer's Disease a , 1996, Annals of the New York Academy of Sciences.

[25]  N Butters,et al.  Episodic memory changes are associated with the APOE- epsilon 4 allele in nondemented older adults , 1995, Neurology.

[26]  G. Alexander,et al.  Regional glucose metabolic abnormalities are not the result of atrophy in Alzheimer's disease , 1998, Neurology.

[27]  J. Laczó,et al.  Human Analogue of the Morris Water Maze for Testing Subjects at Risk of Alzheimer’s Disease , 2010, Neurodegenerative Diseases.

[28]  L. Baxter,et al.  Longitudinal changes in cognition and behavior in asymptomatic carriers of the APOE e4 allele , 2004, Neurology.

[29]  J. Mazziotta,et al.  Cerebral metabolic and cognitive decline in persons at genetic risk for Alzheimer's disease. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[30]  D. T. Vernier,et al.  Restriction isotyping of human apolipoprotein E by gene amplification and cleavage with HhaI. , 1990, Journal of lipid research.

[31]  S. Rapoport,et al.  Functional brain imaging to identify affected subjects genetically at risk for Alzheimer's disease. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[32]  E G Tangalos,et al.  Apolipoprotein E genotype influences cognitive ‘phenotype’ in patients with Alzheimer's disease but not in healthy control subjects , 1998, Neurology.

[33]  J. Haines,et al.  Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families. , 1993, Science.

[34]  Eric M. Reiman,et al.  Preclinical memory decline in cognitively normal apolipoprotein E–ε4 homozygotes , 1999, Neurology.

[35]  M. D’Esposito,et al.  Topographical disorientation: a synthesis and taxonomy. , 1999, Brain : a journal of neurology.

[36]  L. Thal,et al.  Neuropsychological function and apolipoprotein E genotype in the preclinical detection of Alzheimer's disease. , 1999, Psychology and aging.

[37]  P A Parmelee,et al.  Geriatric Depression Scale , 2002 .

[38]  D. Schaid,et al.  Apolipoprotein E status as a predictor of the development of Alzheimer's disease in memory-impaired individuals. , 1995, JAMA.

[39]  D. Selkoe.  In search of X-secretase : Presenilins at the cutting edge , 2000 .

[40]  Adam N Mamelak,et al.  Humans with hippocampus damage display severe spatial memory impairments in a virtual Morris water task , 2002, Behavioural Brain Research.

[41]  Martin Klein,et al.  Cognitive Impairment in Alzheimer’s Disease Is Modified by APOE Genotype , 2007, Dementia and Geriatric Cognitive Disorders.

[42]  R. Parasuraman,et al.  The apolipoprotein E gene, attention, and brain function. , 2002, Neuropsychology.

[43]  Jakub Hort,et al.  Spatial navigation testing discriminates two types of amnestic mild cognitive impairment , 2009, Behavioural Brain Research.

[44]  J. Raber,et al.  Effects of sex and APOE ε4 on object recognition and spatial navigation in the elderly , 2007, Neuroscience.

[45]  J. Bureš,et al.  Spatial navigation deficit in amnestic mild cognitive impairment , 2007, Proceedings of the National Academy of Sciences.