Environmental enrichment improves cognition in aged Alzheimer's transgenic mice despite stable &bgr;-amyloid deposition

Environmental enrichment (EE) has been shown to improve cognitive performance and brain indices of cognition in normal mice and rats. Because the therapeutic potential of intensive, long-term EE to benefit patients with Alzheimer's disease (AD) has yet to be explored, the present study evaluated the effect of long-term EE on cognition in an animal model of AD, the APPsw transgenic mouse. Beginning at 16 months of age, APPsw mice were put into EE or standard housing for 4 months and then tested in four cognitive-based tasks (Morris maze, circular platform, platform recognition, and radial arm water maze) between 20 and 22 months of age. Our results indicate that long-term EE of aged APPsw mice results in global, overall improvement in cognitive function across these tasks without decreasing brain beta-amyloid (A&bgr;) deposition. The results suggest that long-term EE/cognitive stimulation could provide cognitive stabilization or improvement to AD patients through mechanisms independent of A&bgr; deposition and clearance.

[1]  Robert P. Friedland,et al.  Patients with Alzheimer's disease have reduced activities in midlife compared with healthy control-group members , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[2]  D. Diamond,et al.  Progressive, age-related behavioral impairments in transgenic mice carrying both mutant amyloid precursor protein and presenilin-1 transgenes , 2001, Brain Research.

[3]  J. Hardy,et al.  Aβ peptide vaccination prevents memory loss in an animal model of Alzheimer's disease , 2000, Nature.

[4]  D Commenges,et al.  Are sex and educational level independent predictors of dementia and Alzheimer’s disease? Incidence data from the PAQUID project , 1999, Journal of neurology, neurosurgery, and psychiatry.

[5]  B. Shukitt-Hale,et al.  Blueberry Supplementation Enhances Signaling and Prevents Behavioral Deficits in an Alzheimer Disease Model , 2003, Nutritional neuroscience.

[6]  D. Lockhart,et al.  Effects of environmental enrichment on gene expression in the brain. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[7]  A. Granholm,et al.  Long-Term Environmental Enrichment Leads to Regional Increases in Neurotrophin Levels in Rat Brain , 2000, Experimental Neurology.

[8]  M. Hutton,et al.  Multi-metric behavioral comparison of APPsw and P301L models for Alzheimer's Disease: linkage of poorer cognitive performance to tau pathology in forebrain , 2004, Brain Research.

[9]  V. Ramirez-Amaya,et al.  Spatial Long-Term Memory Is Related to Mossy Fiber Synaptogenesis , 2001, The Journal of Neuroscience.

[10]  Satoru Kobayashi,et al.  Effects of enriched environments with different durations and starting times on learning capacity during aging in rats assessed by a refined procedure of the Hebb‐Williams maze task , 2002, Journal of neuroscience research.

[11]  G. Kempermann,et al.  Neuroplasticity in old age: Sustained fivefold induction of hippocampal neurogenesis by long‐term environmental enrichment , 2002, Annals of neurology.

[12]  S. Paul,et al.  α-1-Antichymotrypsin Promotes β-Sheet Amyloid Plaque Deposition in a Transgenic Mouse Model of Alzheimer's Disease , 2001, The Journal of Neuroscience.

[13]  S. Czaja,et al.  Cognitive rehabilitation of mildly impaired Alzheimer disease patients on cholinesterase inhibitors. , 2004, The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry.

[14]  J. G. McCoy,et al.  Environmental enrichment: Effects on spatial memory and hippocampal CREB immunoreactivity , 2001, Physiology & Behavior.

[15]  H. Buschke,et al.  Leisure activities and the risk of dementia in the elderly. , 2003, The New England journal of medicine.

[16]  S. Paul,et al.  Cognitive impairment in PDAPP mice depends on ApoE and ACT-catalyzed amyloid formation , 2004, Neurobiology of Aging.

[17]  R. N. Davis,et al.  Cognitive Intervention in Alzheimer Disease: A Randomized Placebo-Controlled Study , 2001, Alzheimer disease and associated disorders.