Exercise counteracts declining hippocampal function in aging and Alzheimer's disease

Gene Dose of Apolipoprotein E Type 4 Allele and the Risk of Alzheimer's Disease in Late Onset Families

1993 • 8,888 citations

Long‐lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path

1973 • 7,118 citations

Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid β-peptide

2007 • 4,449 citations

Imaging brain amyloid in Alzheimer's disease with Pittsburgh Compound‐B

2004 • 4,223 citations

Correlative Memory Deficits, Aβ Elevation, and Amyloid Plaques in Transgenic Mice

1996 • 4,118 citations

Exercise training increases size of hippocampus and improves memory

2011 • 4,105 citations

Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus

1999 • 3,805 citations

Fitness Effects on the Cognitive Function of Older Adults

2003 • 3,561 citations

Forecasting the global burden of Alzheimer's disease

2007 • 3,191 citations

Neurogenesis in the dentate gyrus of the adult rat: age-related decrease of neuronal progenitor proliferation

1996 • 3,079 citations

Running enhances neurogenesis, learning, and long-term potentiation in mice

1999 • 2,829 citations

Regional Brain Changes in Aging Healthy Adults: General Trends, Individual Differences and Modifiers

2005 • 2,727 citations

Exercise: a behavioral intervention to enhance brain health and plasticity

2002 • 2,571 citations

The projected effect of risk factor reduction on Alzheimer's disease prevalence

2011 • 2,475 citations

Neural consequences of enviromental enrichment

2000 • 2,376 citations

Exercise Enhances Learning and Hippocampal Neurogenesis in Aged Mice

2005 • 2,005 citations

Brain interleukin 1 and S-100 immunoreactivity are elevated in Down syndrome and Alzheimer disease.

1989 • 1,752 citations

2013 Alzheimer's disease facts and figures

2013 • 1,698 citations

Aerobic Exercise and Neurocognitive Performance: A Meta-Analytic Review of Randomized Controlled Trials

2010 • 1,566 citations

Enhanced Neurofibrillary Degeneration in Transgenic Mice Expressing Mutant Tau and APP

2001 • 1,543 citations

Effect of Physical Activity on Cognitive Function in Older Adults at Risk for Alzheimer Disease

2008 • 1,529 citations

Transcriptional Paradigms in Mammalian Mitochondrial Biogenesis and Function

2008 • 1,461 citations

Exercise Is Associated with Reduced Risk for Incident Dementia among Persons 65 Years of Age and Older

2006 • 1,444 citations

Hippocampal long-term potentiation is impaired in mice lacking brain-derived neurotrophic factor.

1995 • 1,416 citations

Hippocampal BDNF mediates the efficacy of exercise on synaptic plasticity and cognition

2004 • 1,345 citations

An in vivo correlate of exercise-induced neurogenesis in the adult dentate gyrus

2007 • 1,288 citations

Recombinant BDNF Rescues Deficits in Basal Synaptic Transmission and Hippocampal LTP in BDNF Knockout Mice

1996 • 1,219 citations

The effects of exercise training on elderly persons with cognitive impairment and dementia: A meta-analysis11No commercial party having a direct financial interest in the results of the research supporting this article has or will confer a benefit upon the author(s) or upon any organization with which the author(s) is/are associated.

2004 • 1,206 citations

Alzheimer's disease: clinical trials and drug development

2010 • 1,152 citations

Learning causes synaptogenesis, whereas motor activity causes angiogenesis, in cerebellar cortex of adult rats.

1990 • 1,142 citations

Physical activity and risk of cognitive decline: a meta-analysis of prospective studies

2010 • 1,072 citations

Effects of Aerobic Exercise on Mild Cognitive Impairment

2010 • 1,066 citations

Leisure-time physical activity at midlife and the risk of dementia and Alzheimer's disease

2005 • 1,043 citations

Oxidative damage to mitochondrial DNA is increased in Alzheimer's disease

1994 • 1,020 citations

Production of interleukin‐6 in contracting human skeletal muscles can account for the exercise‐induced increase in plasma interleukin‐6

2000 • 984 citations

Circulating Insulin-Like Growth Factor I Mediates Exercise-Induced Increases in the Number of New Neurons in the Adult Hippocampus

2001 • 976 citations

Immune function in sport and exercise

2007 • 952 citations

Aerobic fitness is associated with hippocampal volume in elderly humans

2009 • 940 citations

2011 Alzheimer's disease facts and figures

2011 • 907 citations

Physical activity and risk of neurodegenerative disease: a systematic review of prospective evidence

2008 • 890 citations

BDNF mRNA is decreased in the hippocampus of individuals with Alzheimer's disease

1991 • 887 citations

Physical Activity, Diet, and Risk of Alzheimer Disease

2009 • 875 citations

Environmental Enrichment Reduces Aβ Levels and Amyloid Deposition in Transgenic Mice

2005 • 859 citations

VEGF links hippocampal activity with neurogenesis, learning and memory

2004 • 815 citations

VEGF is necessary for exercise‐induced adult hippocampal neurogenesis

2003 • 801 citations

Physical Exercise as a Preventive or Disease-Modifying Treatment of Dementia and Brain Aging

2011 • 793 citations

APOE predicts amyloid‐beta but not tau Alzheimer pathology in cognitively normal aging

2009 • 785 citations

Brain Regional Correspondence Between Alzheimer's Disease Histopathology and Biomarkers of Protein Oxidation

1995 • 784 citations

Voluntary Exercise Decreases Amyloid Load in a Transgenic Model of Alzheimer's Disease

2005 • 769 citations

Oxidative damage to mitochondrial DNA shows marked age‐dependent increases in human brain

1993 • 759 citations

Reversal of age-related increase in brain protein oxidation, decrease in enzyme activity, and loss in temporal and spatial memory by chronic administration of the spin-trapping compound N-tert-butyl-alpha-phenylnitrone.

1991 • 734 citations

Exercise and IL‐6 infusion inhibit endotoxin‐induced TNF‐α production in humans

2003 • 730 citations

Coordinated Interaction of Neurogenesis and Angiogenesis in the Adult Songbird Brain

2002 • 718 citations

Impact of aging on hippocampal function: plasticity, network dynamics, and cognition

2003 • 711 citations

Inflammatory markers and cognition in well-functioning African-American and white elders

2003 • 686 citations

Total daily physical activity and the risk of AD and cognitive decline in older adults

2012 • 636 citations

Persistence of Long-Term Memory Storage Requires a Late Protein Synthesis- and BDNF- Dependent Phase in the Hippocampus

2007 • 616 citations

Environmental enrichment and voluntary exercise massively increase neurogenesis in the adult hippocampus via dissociable pathways

2006 • 559 citations

Alzheimer's brains harbor somatic mtDNA control-region mutations that suppress mitochondrial transcription and replication

2004 • 537 citations

Insulin-like growth factor I interfaces with brain-derived neurotrophic factor-mediated synaptic plasticity to modulate aspects of exercise-induced cognitive function

2006 • 516 citations

Memory loss in old rats is associated with brain mitochondrial decay and RNA/DNA oxidation: Partial reversal by feeding acetyl- <scp>l</scp> -carnitine and/or R -α-lipoic acid

2002 • 510 citations

Physical activity and memory functions: An interventional study

2009 • 477 citations

Physical activity predicts gray matter volume in late adulthood

2010 • 472 citations

Beneficial effects of moderate exercise on mice aging: survival, behavior, oxidative stress, and mitochondrial electron transfer

2004 • 462 citations

Physical exercise prevents age-related decline in precursor cell activity in the mouse dentate gyrus

2005 • 461 citations

Exercise primes a molecular memory for brain-derived neurotrophic factor protein induction in the rat hippocampus

2005 • 455 citations

Differential effects of acute and chronic exercise on plasticity‐related genes in the rat hippocampus revealed by microarray

2002 • 433 citations

RETRACTED: SIRT1 Suppresses β-Amyloid Production by Activating the α-Secretase Gene ADAM10

2010 • 429 citations

Interleukin-1β (IL-1β) and tumour necrosis factor (TNF) inhibit long-term potentiation in the rat dentate gyrus in vitro

1996 • 425 citations

Additive effects of physical exercise and environmental enrichment on adult hippocampal neurogenesis in mice

2009 • 402 citations

Differential Expression of Oxidative Phosphorylation Genes in Patients With Alzheimer's Disease: Implications for Early Mitochondrial Dysfunction and Oxidative Damage

2004 • 398 citations

Regular exercise improves cognitive function and decreases oxidative damage in rat brain

2001 • 376 citations

Running is the neurogenic and neurotrophic stimulus in environmental enrichment

2011 • 366 citations

Microglia and inflammatory mechanisms in the clearance of amyloid β peptide

2002 • 365 citations

Cardiorespiratory fitness and brain atrophy in early Alzheimer disease

2008 • 363 citations

Oxidative stress in Alzheimer's disease brain: New insights from redox proteomics

2006 • 357 citations

PGC-1α Expression Decreases in the Alzheimer Disease Brain as a Function of Dementia

2009 • 352 citations

Virus-mediated gene transfer into hippocampal CA1 region restores long-term potentiation in brain-derived neurotrophic factor mutant mice.

1996 • 350 citations

Can Cognitive Exercise Prevent the Onset of Dementia? Systematic Review of Randomized Clinical Trials with Longitudinal Follow-up

2009 • 333 citations

Effects of Exercise on Gene-Expression Profile in the Rat Hippocampus

2001 • 329 citations

Intracerebral production of tumor necrosis factor-alpha, a local neuroprotective agent, in Alzheimer disease and vascular dementia.

1999 • 328 citations

Inflammation in Alzheimer's disease: Amyloid-β oligomers trigger innate immunity defence via pattern recognition receptors

2009 • 325 citations

Presynaptic BDNF Required for a Presynaptic but Not Postsynaptic Component of LTP at Hippocampal CA1-CA3 Synapses

2003 • 325 citations

Amyloid‐β associated cortical thinning in clinically normal elderly

2010 • 316 citations

Brain-Derived Neurotrophic Factor Promotes Long-Term Potentiation-Related Cytoskeletal Changes in Adult Hippocampus

2007 • 313 citations

Exercise and Alzheimer's disease biomarkers in cognitively normal older adults

2010 • 311 citations

Voluntary exercise and caloric restriction enhance hippocampal dendritic spine density and BDNF levels in diabetic mice

2009 • 311 citations

Regional Effects of Wheel Running and Environmental Enrichment on Cell Genesis and Microglia Proliferation in the Adult Murine Neocortex

2003 • 308 citations

Exercise training increases mitochondrial biogenesis in the brain

2011 • 304 citations

Gender differences in the amount and deposition of amyloidβ in APPswe and PS1 double transgenic mice

2003 • 282 citations

Serum TNF-alpha levels are increased and correlate negatively with free IGF-I in Alzheimer disease

2006 • 266 citations

Physical activity and cognitive decline, the role of the apolipoprotein e4 allele

2001 • 262 citations

Augmented Senile Plaque Load in Aged Female β-Amyloid Precursor Protein-Transgenic Mice

2001 • 260 citations

The exercise-induced expression of BDNF within the hippocampus varies across life-span

2005 • 256 citations

Memory for context is impaired by a post context exposure injection of interleukin-1 beta into dorsal hippocampus

2002 • 254 citations

BDNF serum and CSF concentrations in Alzheimer’s disease, normal pressure hydrocephalus and healthy controls

2006 • 254 citations

Exercise Engagement as a Moderator of the Effects of &lt;emph type="ital"&gt;APOE&lt;/emph&gt; Genotype on Amyloid Deposition

2012 • 253 citations

Contribution of Metabolic Syndrome Components to Cognition in Older Individuals

2007 • 248 citations

Abnormal tau, mitochondrial dysfunction, impaired axonal transport of mitochondria, and synaptic deprivation in Alzheimer's disease

2011 • 248 citations

Exercise and Toll-like receptors.

2006 • 247 citations

Age-Related Activation of Microglia and Astrocytes: In Vitro Studies Show Persistent Phenotypes of Aging, Increased Proliferation, and Resistance to Down-Regulation

1998 • 246 citations

Effects of voluntary and forced exercise on plaque deposition, hippocampal volume, and behavior in the Tg2576 mouse model of Alzheimer's disease

2009 • 240 citations

Effects of environmental enrichment and voluntary exercise on neurogenesis, learning and memory, and pattern separation: BDNF as a critical variable?

2011 • 239 citations

Physical Exercise Protects Against Alzheimer's Disease in 3xTg-AD Mice

2011 • 232 citations

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

2004 • 231 citations

Exercise alters the immune profile in Tg2576 Alzheimer mice toward a response coincident with improved cognitive performance and decreased amyloid

2008 • 224 citations

Exercise moderates age-related atrophy of the medial temporal lobe

2009 • 221 citations

Brain-Derived Neurotrophic Factor-Dependent Synaptic Plasticity Is Suppressed by Interleukin-1β via p38 Mitogen-Activated Protein Kinase

2012 • 217 citations

Peripheral Nerve Injury Leads to Working Memory Deficits and Dysfunction of the Hippocampus by Upregulation of TNF-α in Rodents

2011 • 217 citations

Environmental Enrichment Exacerbates Amyloid Plaque Formation in a Transgenic Mouse Model of Alzheimer Disease

2003 • 214 citations

Comparative signaling pathways of insulin‐like growth factor‐1 and brain‐derived neurotrophic factor in hippocampal neurons and the role of the PI3 kinase pathway in cell survival

2004 • 213 citations

Enrichment improves cognition in AD mice by amyloid-related and unrelated mechanisms

2006 • 212 citations

Cardiorespiratory Fitness and Preserved Medial Temporal Lobe Volume in Alzheimer Disease

2009 • 209 citations

Exercise improves cognition and hippocampal plasticity in APOE ɛ4 mice

2009 • 200 citations

Complex Mental and Physical Activity in Older Women and Cognitive Performance: A 6-month Randomized Controlled Trial

2010 • 196 citations

Treadmill exercise represses neuronal cell death in an aged transgenic mouse model of Alzheimer's disease

2010 • 195 citations

Influence of Physical Activity on Serum IL-6 and IL-10 Levels in Healthy Older Men

2004 • 195 citations

A dual role for interleukin-1 in LTP in mouse hippocampal slices

2003 • 193 citations

Exercise training acts as a therapeutic strategy for reduction of the pathogenic phenotypes for Alzheimer's disease in an NSE/APPsw-transgenic model

1998 • 191 citations

Interleukin‐6 release from the human brain during prolonged exercise

2002 • 189 citations

Short-term exercise in aged Tg2576 mice alters neuroinflammation and improves cognition

2008 • 188 citations

Time course of oxidative damage in different brain regions following transient cerebral ischemia in gerbils

2001 • 187 citations

The association between systemic inflammation and cognitive performance in the elderly: the Sydney Memory and Ageing Study

2011 • 182 citations

Moderate exercise improves antibody response to influenza immunization in older adults

2003 • 176 citations

Exercise-Induced Changes in Local Cerebral Glucose Utilization in the Rat

1996 • 173 citations

Anxiety- and depression-like behaviors are accompanied by an increase in oxidative stress in a rat model of fetal alcohol spectrum disorders: Protective effects of voluntary physical exercise

2011 • 169 citations

Cardiovascular Exercise Training Extends Influenza Vaccine Seroprotection in Sedentary Older Adults: The Immune Function Intervention Trial

2009 • 167 citations

Wheel running attenuates microglia proliferation and increases expression of a proneurogenic phenotype in the hippocampus of aged mice

2011 • 166 citations

Exercise affects energy metabolism and neural plasticity‐related proteins in the hippocampus as revealed by proteomic analysis

2006 • 165 citations

APOE E4 status predicts age-related cognitive decline in the ninth decade: longitudinal follow-up of the Lothian Birth Cohort 1921

2011 • 159 citations

Coupling energy metabolism with a mechanism to support brain-derived neurotrophic factor-mediated synaptic plasticity

2006 • 158 citations

Exercise-Induced Synaptogenesis in the Hippocampus Is Dependent on UCP2-Regulated Mitochondrial Adaptation

2008 • 155 citations

Activity Energy Expenditure and Incident Cognitive Impairment in Older Adults

2011 • 153 citations

Regional responses in antioxidant system to exercise training and dietary Vitamin E in aging rat brain

2003 • 152 citations

Beneficial effects of exercise in a transgenic mouse model of Alzheimer's disease-like Tau pathology

2011 • 150 citations

The effects of moderate-, strenuous- and over-training on oxidative stress markers, DNA repair, and memory, in rat brain

2005 • 150 citations

Convergence of Amyloid-β and Tau Pathologies on Mitochondria In Vivo

2010 • 149 citations

Chronic endurance exercise training prevents aging‐related cognitive decline in healthy older adults: a randomized controlled trial

2009 • 145 citations

Treadmill exercise prevents decline in spatial learning and memory in APP/PS1 transgenic mice through improvement of hippocampal long-term potentiation

2010 • 144 citations

Mitochondrial complex I defects in aging.

1997 • 143 citations

Memantine reduces oxidative damage and enhances long-term recognition memory in aged rats

2007 • 139 citations

The Effect of Exercise on the Cerebral Vasculature of Healthy Aged Subjects as Visualized by MR Angiography

2009 • 136 citations

BDNF increases rat brain mitochondrial respiratory coupling at complex I, but not complex II

2004 • 134 citations

The effects on cognitive functions of a movement-based intervention in patients with Alzheimer's type dementia: a pilot study

2010 • 132 citations

Environmental enrichment, exercise and corticosterone affect endothelial cell proliferation in adult rat hippocampus and prefrontal cortex

2008 • 132 citations

Multiple Hormonal Deficiencies in Anabolic Hormones Are Found in Frail Older Women: The Women's Health and Aging Studies

2009 • 132 citations

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1997 • 131 citations

C-reactive protein is related to memory and medial temporal brain volume in older adults

2011 • 129 citations

Resting hippocampal blood flow, spatial memory and aging

2009 • 126 citations

Epigenetic Enhancement of BDNF Signaling Rescues Synaptic Plasticity in Aging

2011 • 122 citations

Cognitive Performance in Older Women Relative to ApoE-ε4 Genotype and Aerobic Fitness

2007 • 121 citations

Effects of muscle strength and aerobic training on basal serum levels of IGF-1 and cortisol in elderly women

2009 • 121 citations

BDNF-induced LTP in dentate gyrus is impaired with age: analysis of changes in cell signaling events

2004 • 118 citations

Effect of aerobic training on the cognitive performance of elderly patients with senile dementia of alzheimer type

1996 • 115 citations

Different types of exercise induce differential effects on neuronal adaptations and memory performance

2011 • 113 citations

Melatonin plus physical exercise are highly neuroprotective in the 3xTg-AD mouse

2011 • 109 citations

Differences in survival‐promoting effects and intracellular signaling properties of BDNF and IGF‐1 in cultured cerebral cortical neurons

2001 • 109 citations

Redox proteomics in aging rat brain: Involvement of mitochondrial reduced glutathione status and mitochondrial protein oxidation in the aging process

2010 • 108 citations

Exercise, but not environmental enrichment, improves learning after kainic acid-induced hippocampal neurodegeneration in association with an increase in brain-derived neurotrophic factor

2004 • 105 citations

Exercise, APOE, and working memory: MEG and behavioral evidence for benefit of exercise in epsilon4 carriers

2008 • 105 citations

Effects of aerobic and strength-based training on metabolic health indicators in older adults

2010 • 103 citations

Running reduces stress and enhances cell genesis in aged mice

2010 • 103 citations

Repression of tau hyperphosphorylation by chronic endurance exercise in aged transgenic mouse model of tauopathies

2009 • 98 citations

Physical Activity and Alzheimer Disease Course

2010 • 98 citations

Feasibility [corrected] of regular physical exercise for patients with moderate to severe Alzheimer disease.

2000 • 93 citations

Positron Emission Tomography Radiopharmaceuticals for Imaging Brain Beta-Amyloid

2011 • 90 citations

Gender-Specific Neuroimmunoendocrine Response to Treadmill Exercise in 3xTg-AD Mice

2010 • 90 citations

Long-term treadmill exercise induces neuroprotective molecular changes in rat brain

2011 • 89 citations

Environmental enrichment stimulates neurogenesis in apolipoprotein E3 and neuronal apoptosis in apolipoprotein E4 transgenic mice

2006 • 88 citations

Reduction of Amyloid Angiopathy and Aβ Plaque Burden after Enriched Housing in TgCRND8 Mice

2006 • 86 citations

Voluntary Running and Environmental Enrichment Restores Impaired Hippocampal Neurogenesis in a Triple Transgenic Mouse Model of Alzheimers Disease

2011 • 83 citations

Uncoupling protein-2 accumulates rapidly in the inner mitochondrial membrane during mitochondrial reactive oxygen stress in macrophages

2007 • 75 citations

Brain regional angiogenic potential at the neurovascular unit during normal aging

2011 • 73 citations

Exercise training alters kinetics of antioxidant enzymes in rat tissues.

1996 • 73 citations

Voluntary exercise induces adult hippocampal neurogenesis and BDNF expression in a rodent model of fetal alcohol spectrum disorders

2011 • 72 citations

Blood Leukocyte mRNA Expression for IL-10, IL-1Ra, and IL-8, but Not IL-6, Increases After Exercise

2006 • 72 citations

BDNF-, IGF-1- and GDNF-Secreting Human Neural Progenitor Cells Rescue Amyloid β-Induced Toxicity in Cultured Rat Septal Neurons

2011 • 71 citations

Body mass index, free insulin-like growth factor I, and physical function among older adults: results from the ilSIRENTE study

2006 • 69 citations

BDNF Facilitates L-LTP Maintenance in the Absence of Protein Synthesis through PKMζ

2011 • 67 citations

Cardiovascular exercise intervention improves the primary antibody response to keyhole limpet hemocyanin (KLH) in previously sedentary older adults

2008 • 61 citations

Mitochondrial DNA shifting in older adults following resistance exercise trainingThis paper article is one of a selection of papers published in this Special Issue, entitled 14th International Biochemistry of Exercise Conference – Muscles as Molecular and Metabolic Machines, and has undergone the Journal’s usual peer review process.

2009 • 60 citations

Neural protein synthesis during aging: effects on plasticity and memory

2010 • 51 citations

Uncoupling protein 2 regulates reactive oxygen species formation in islets and influences susceptibility to diabetogenic action of streptozotocin

2009 • 49 citations

Insulin-like growth factor I stimulate angiogenesis and the production of vascular endothelial growth factor

2000 • 47 citations

Plasma antioxidant activity and cutaneous microvascular endothelial function in athletes and sedentary controls

2004 • 46 citations

Decreased Release of the Angiogenic Peptide Vascular Endothelial Growth Factor in Alzheimer’s Disease: Recovering Effect with Insulin and DHEA Sulfate

2004 • 41 citations

UCP2 protects hypothalamic cells from TNF‐α‐induced damage

2008 • 32 citations

Aerobic Performance and Antioxidant Protection in Runners

2009 • 28 citations

Alzheimer's - Looking beyond plaques

2011 • 20 citations

Cardiovascular fitness is associated with altered cortical glucose metabolism during working memory in ε4 carriers

2012 • 18 citations

Plasma antioxidant activity and cutaneous microvascular endothelial function in athletes and sedentary controls

2004 • 14 citations

Proxy reports of physical activity were valid in older people with and without cognitive impairment

2009 • 11 citations

Impairment of secretory pattern of IGF-I from lymphomononuclear cells in aging and dementia of the Alzheimer's and vascular type.

2002 • 4 citations