No effective treatments are currently available for the prevention or cure of Alzheimer’s disease (AD), the most frequent form of dementia in the elderly. The most recognized risk factors, advancing age and having the apolipoprotein E Ɛ4 gene, cannot be modified or treated. Increasingly, scientists are looking toward other risk factors to identify preventive and therapeutic strategies. Much attention recently has focused on the metabolic syndrome (MetS), with a strong and growing body of research suggesting that metabolic disorders and obesity may play a role in the development of dementia.
A new supplement to the Journal of Alzheimer’s Disease provides a state-of-the-art assessment of research into the link between metabolic syndrome and cognitive disorders. The supplement is guest edited by Vincenza Frisardi, of the Department of Neurological and Psychiatric Sciences, University of Bari, and the Geriatric Unit and Gerontology-Geriatrics Research Laboratory, IRCCS, Foggia, Italy, and Bruno P. Imbimbo, Research and Development Department, Chiesi Farmaceutici, Parma, Italy.
The prevalence of MetS and obesity has increased over the past several decades. MetS is a cluster of vascular and metabolic risk factors including obesity, hypertension, an abnormal cholesterol profile, and impaired blood glucose regulation. “Although molecular mechanisms underlying the relationship between MetS and neurological disorders are not fully understood, it is becoming increasingly clear that cellular and biochemical alterations observed in MetS may represent a pathological bridge between MetS and various neurological disorders,” explains Dr. Frisardi.
Type 2 diabetes (T2D) has been linked with cognitive impairment in a number of studies. The risk for developing both T2D and AD increases proportionately with age, and evidence shows that individuals with T2D have a nearly twofold higher risk of AD than nondiabetic individuals.
Paula I. Moreira, Faculty of Medicine and Center for Neuroscience and Cell Biology, University of Coimbra, Portugal, outlines some of the likely mechanisms. Both AD and T2D present similar abnormalities in the mitochondria, which play a pivotal role in cellular processes that impair their ability to regulate oxidation in the cell. Human amylin, a peptide that forms deposits in the pancreatic cells of T2D patients, shares several properties with amyloid-ß plaques in the Alzheimer’s brain. Insulin resistance is another feature shared by both disorders. Impairment of insulin signalling is directly involved in the development of tau tangles and amyloid ß (Aß) plaques. “Understanding the key mechanisms underlying this deleterious interaction may provide opportunities for the design of effective therapeutic strategies,” Dr. Moreira notes.
In another article, author, José A. Luchsinger of the Division of General Medicine, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, notes that while there seems to be little dispute that T2D can cause cerebrovascular disease and vascular cognitive impairment, whether T2D can cause late onset AD remains to be determined. “Although the idea is highly speculative, the association between T2D and cognitive impairment may not be causal. Several lines of evidence provide some support to the idea that late onset Alzheimer’s disease could cause T2D, or that both could share causal pathways,” he notes. He reviews epidemiological, imaging, and pathological studies and clinical trials to provide insight. “Given the epidemic of T2D in the world, it’s important to determine whether the association between T2D and cognitive impairment, particularly late onset AD, is causal and if so, what are the mechanisms underlying it.”
Dr. Frisardi notes that most efforts by the pharmaceutical industry have been directed against the production and accumulation of amyloid-ß. “Unfortunately, these efforts have not produced effective therapies yet, since the exact mechanisms of AD are largely unknown. Given that the onset of AD most likely results from the interaction of genetic and environmental factors, the research agenda should consider new platforms of study, going beyond the monolithic outlook of AD, by synthesizing epidemiological, experimental, and biological data under a unique pathophysiological model as a point of reference for further advances in the field.”
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NOTES FOR EDITORS
Metabolic-Cognitive Syndrome: Update on the Metabolic Pathway in Neurodegenerative Disorders
Guest Editors: Vincenza Frisardi and Bruno P. Imbimbo
Journal of Alzheimer’s Disease, Volume 30 (2012), Supplement 2
Full text of the articles in the Supplement is available to credentialed journalists upon request. Contact Daphne Watrin, IOS Press at +31 20 688 3355, firstname.lastname@example.org to obtain a copy. To request an author interview contact Dr. Vincenza Frisardi at email@example.com.
Table of Contents
Metabolic-Cognitive Syndrome: Metabolic Approach for the Management of Alzheimer’s Disease Risk
V. Frisardi, B.P. Imbimbo
Metabolic Reserve as a Determinant of Cognitive Aging
A.M. Stranahan, M.P. Mattson
The “LEARn” (Latent Early-life Associated Regulation) Model: An Epigenetic Pathway Linking Metabolic and Cognitive Disorders
D.K. Lahiri, B. Maloney
Current Epidemiological Approaches to the Metabolic-Cognitive Syndrome
F. Panza, V. Solfrizzi, G. Logroscino, et al.
Metabolic Syndrome, Cognitive Performance, and Dementia
G. E. Crichton, M. F. Elias, J.D. Buckley, et al.
Cognitive Function and Decline in Obesity
K. Stanek Sellbom, J. Gunstad
Adiposity and Cognitive Decline: Underlying Mechanisms
Obesity, Cognitive Functioning and Dementia: Back to the Future
M.F. Elias, A.L Goodell, S. R Waldstein
Dyslipidemia and Dementia: Current Epidemiology, Genetic Evidence, and Mechanisms Behind the Associations
Cholesterol and Late-Life Cognitive Decline
P. van Vliet
Lipid Mediators and Their Metabolism in the Nucleus: Implications for Alzheimer’s Disease
The Saturated Fatty Acid Palmitate Induces Human Monocytic Cell Toxicity Toward Neuronal Cells: Exploring a Possible Link Between Obesity-Related Metabolic Impairments and Neuroinflammation
J.P. Little, J.M. Madeira, A. Klegeris
Type 2 Diabetes and Cognitive Impairment: Linking Mechanisms
Alzheimer’s Disease and Diabetes: An Integrative View of the Role of Mitochondria, Oxidative Stress, and Insulin
Dysfunctional Pro-Ceramide, ER Stress, and Insulin/IGF Signaling Networks with Progression of Alzheimer’s Disease
S.M. de la Monte, E. Re, L. Longato, et al.
Triangulated Mal-signaling in Alzheimer’s Disease: Roles of Neurotoxic Ceramides, ER Stress, and Insulin Resistance Reviewed
S.M. de la Monte
The Renin-Angiotensin System and Antihypertensive Drugs in Alzheimer’s Disease: Current Standing of the Angiotensin Hypothesis?
P.G Kehoe, P.A. Passmore
Calcium Channel Blockers and Alzheimer’s Disease: Potential Relevance in Treatment Strategies of Metabolic Syndrome
W.V. Goodison, V. Frisardi, P.G. Kehoe
Apolipoprotein E Genotype: The Innocent Bystander or Active Bridge between Metabolic Syndrome and Cognitive Impairment?
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