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      Dissociating Normal Aging from Alzheimer’s Disease: A View from Cognitive Neuroscience

      review-article
      a , b , *
      Journal of Alzheimer's Disease
      IOS Press
      Activation, aging, Alzheimer’s disease, atrophy, cognition, connectivity, fractional anisotropy, mean diffusivity, structural integrity, volume

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          Abstract

          Both normal aging and Alzheimer’s disease (AD) are associated with changes in cognition, grey and white matter volume, white matter integrity, neural activation, functional connectivity, and neurotransmission. Obviously, all of these changes are more pronounced in AD and proceed faster providing the basis for an AD diagnosis. Since these differences are quantitative, however, it was hypothesized that AD might simply reflect an accelerated aging process. The present article highlights the different neurocognitive changes associated with normal aging and AD and shows that, next to quantitative differences, there are multiple qualitative differences as well. These differences comprise different neurocognitive dissociations as different cognitive deficit profiles, different weights of grey and white matter atrophy, and different gradients of structural decline. These qualitative differences clearly indicate that AD cannot be simply described as accelerated aging process but on the contrary represents a solid entity.

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          Most cited references178

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          Alzheimer's disease.

          Alzheimer's disease is the most common cause of dementia. Research advances have enabled detailed understanding of the molecular pathogenesis of the hallmarks of the disease--ie, plaques, composed of amyloid beta (Abeta), and tangles, composed of hyperphosphorylated tau. However, as our knowledge increases so does our appreciation for the pathogenic complexity of the disorder. Familial Alzheimer's disease is a very rare autosomal dominant disease with early onset, caused by mutations in the amyloid precursor protein and presenilin genes, both linked to Abeta metabolism. By contrast with familial disease, sporadic Alzheimer's disease is very common with more than 15 million people affected worldwide. The cause of the sporadic form of the disease is unknown, probably because the disease is heterogeneous, caused by ageing in concert with a complex interaction of both genetic and environmental risk factors. This seminar reviews the key aspects of the disease, including epidemiology, genetics, pathogenesis, diagnosis, and treatment, as well as recent developments and controversies.
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            Hemispheric asymmetry reduction in older adults: the HAROLD model.

            A model of the effects of aging on brain activity during cognitive performance is introduced. The model is called HAROLD (hemispheric asymmetry reduction in older adults), and it states that, under similar circumstances, prefrontal activity during cognitive performances tends to be less lateralized in older adults than in younger adults. The model is supported by functional neuroimaging and other evidence in the domains of episodic memory, semantic memory, working memory, perception, and inhibitory control. Age-related hemispheric asymmetry reductions may have a compensatory function or they may reflect a dedifferentiation process. They may have a cognitive or neural origin, and they may reflect regional or network mechanisms. The HAROLD model is a cognitive neuroscience model that integrates ideas and findings from psychology and neuroscience of aging.
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              A review on Alzheimer's disease pathophysiology and its management: an update.

              Alzheimer's disease acknowledged as progressive multifarious neurodegenerative disorder, is the leading cause of dementia in late adult life. Pathologically it is characterized by intracellular neurofibrillary tangles and extracellular amyloidal protein deposits contributing to senile plaques. Over the last two decades, advances in the field of pathogenesis have inspired the researchers for the investigation of novel pharmacological therapeutics centered more towards the pathophysiological events of the disease. Currently available treatments i.e. acetylcholinesterase inhibitors (rivastigmine, galantamine, donepezil) and N-methyl d-aspartate receptor antagonist (memantine) contribute minimal impact on the disease and target late aspects of the disease. These drugs decelerate the progression of the disease, provide symptomatic relief but fail to achieve a definite cure. While the neuropathological features of Alzheimer's disease are recognized but the intricacies of the mechanism have not been clearly defined. This lack of understanding regarding the pathogenic process may be the likely reason for the non-availability of effective treatment which can prevent onset and progression of the disease. Owing to the important progress in the field of pathophysiology in the last couple of years, new therapeutic targets are available that should render the underlying disease process to be tackled directly. In this review, authors will discusses the different aspects of pathophysiological mechanisms behind Alzheimer's disease and its management through conventional drug therapy, including modern investigational therapeutic strategies, recently completed and ongoing.
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                Author and article information

                Journal
                J Alzheimers Dis
                J. Alzheimers Dis
                JAD
                Journal of Alzheimer's Disease
                IOS Press (Nieuwe Hemweg 6B, 1013 BG Amsterdam, The Netherlands )
                1387-2877
                1875-8908
                25 February 2017
                21 March 2017
                2017
                : 57
                : 2
                : 331-352
                Affiliations
                [a ]Department of Psychiatry and Psychotherapy Bethel, Research Division, Evangelisches Krankenhaus Bielefeld (EvKB) , Bielefeld, Germany
                [b ]Department of Psychiatry and Psychotherapy Bethel, Department of Geriatric Psychiatry, Evangelisches Krankenhaus Bielefeld (EvKB) , Bielefeld, Germany
                Author notes
                [* ]Correspondence to: Dr. Max Toepper, Evangelisches Krankenhaus Bielefeld (EvKB), Klinik für Psychiatrie und Psychotherapie Bethel, Haus Gilead IV, Forschungsabteilung, Dr. Max Toepper, Remterweg 69-71, D-33617 Bielefeld, Germany. Tel.: +49 521 77278521; Fax: +49 521 77278511; E-mail: max.toepper@ 123456evkb.de .
                Article
                JAD161099
                10.3233/JAD-161099
                5366251
                28269778
                ede3eb18-9b6b-4c9f-b5b5-2b10d72640b6
                IOS Press and the authors. All rights reserved

                This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial (CC BY-NC 4.0) License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 23 January 2017
                Categories
                Review

                activation,aging,alzheimer’s disease,atrophy,cognition,connectivity,fractional anisotropy,mean diffusivity,structural integrity,volume

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