Abstracts / Neurobiology of Aging 35 (2014) 715–724 717

Objectives. In this study, we investigated the interrelationship betweenclinical variables and working memory (WM) in Parkinson’s disease (PD).Specifically, the aim of the study was to investigate the relationship be-tween disease duration, dopaminergic medication dosage, and motordisability (UPDRS score) with WM in individuals with PD.Methods. We recruited three groups of subjects: unmedicated PD pa-tients, medicated PD patients, and healthy controls. All subjects weretested on three WM tasks: short-delay WM, long-delay WM, and the n-back task. Further, PD encompasses a spectrum that can be classified eitherinto akinesia/rigidity or resting tremor as the predominant motor pre-sentation of the disease. In addition to studying medication effects, wetested WM performance in tremor-dominant and akinesia-dominant pa-tients. We further correlated WM performance with disease duration andmedication dosage.Results. We found no difference between medicated and unmedicatedpatients in the short-delayWM task, but medicated patients outperformedunmedicated patients in the long-delay WM and n-back tasks. Interest-ingly, we also found that akinesia-dominant patients were more impairedthan tremor-dominant patients at various WM measures, which is inagreement with prior studies of the relationship between akinesiasymptom and basal ganglia dysfunction. Moreover, the results show thatdisease duration inversely correlates with more demanding WM tasks(long-delay WM and n-back tasks), but medication dosage positivelycorrelates with demanding WM performance.Conclusions. Our results show that WM impairment in PD patientsdepend on cognitive domain (simple vs.demanding WM task), subtype ofPD patients (tremor- vs. akinesia-dominant), as well as disease durationand medication dosage. Our results have implications for the interrela-tionship between motor and cognitive processes in PD, and for under-standing the role of cognitive training in treating motor symptoms in PD.

Molecular Aspects

HEALTHY BRAIN AGING AND THE MULTIPLE RESERVE HYPOTHESIS

Robert Frıedland. University of Louisville, Department of Neurology,Louisvile, Kentucky, USA

Those of us in the medical professions are trained since early years to beconcerned about the many forms and mechanisms of disease. We strive tobe aggressive in our diagnosis and treatment of disease and in our researchon disease mechanisms, known as pathogenesis. Often lost in our diseasefocused frame of mind is appreciation for the generation and maintenanceof health, known as salutogenesis. The absence of disease is not the sameas the presence of health, especially with aging. Many older people do nothave major illnesses, but remain limited in their functional capacities. It isvital for persons of all ages, as well as their physicians, to be aware of thisperspective and to enhance fitness in its many forms: cerebral, physical,social, psychological and spiritual. Enhanced fitness in these domainsprovides enhanced resistance to disease development. The presence of astroke accelerates development of Alzheimer dementia. Mental activity inmidlife, as well as education in early life, is related to Alzheimer risk.Furthermore, the ability to maintain cerebral function is dependent ongood functioning of the heart, kidneys and lungs, as well as other organs.People who are married and have good social support systems have alower risk of dementiawith aging. Depression in midlife is also a risk factorfor cognitive impairment. We found that Arab women who pray have alower risk of cognitive decline (Curr Alzheimer Res 2013;10:340-6).Physical fitness has also been linked to cognitive function with aging. Themultiple reserve hypothesis postulates that the quality of life in aging isdetermined by the ability to resist loss of function which accompaniessenescence. And this ability to maintain function is determined by thereserve capacities present in the brain, as well as all other organ systems,and the social, psychological and spiritual features of a person’s life. The USNational Library of Medicine shows 473 citations (9/20/2013) for thephrase ‘cognitive reserve’, which is undoubtedly a critical concept. We areconcerned that the additional reserves we discuss are not properlyrecognized for their important contributions to salutogenesis with aging.Furthermore, the concept of reserves often focuses onmidlife, because that

is the period most amenable to study. Cerebral, physical, social, psycho-logical and spiritual reserves are all related to early life events, which play acritical role in determining the quality of life with aging (J Dev BehavPediatr 2009;3:239-41).

THE ROLE OF TNF-ALPHA IN NEURODEGENERATION

Abdu Adem. United Arab Emirates University, College of Medicine and HealthSciences, Department of Pharmacology and Therapeutics, Al Ain, United ArabEmirates

Objectives. We have shown previously, that mice lacking tumor necrosisfactor-a (TNF-a) receptor 1 (TNFR1) exhibit greater hippocampal neuro-degeneration, suggesting that TNFR1may be protective in kainic acid (KA)-induced neurotoxicity. Here, we aim to clarify the role of TNF-a inneurodegenerative disorders and to elucidate its potential signalingpathways.Methods. TNF-a[1] knockout (KO) mice and wild-type (WT) mice weretreated with KA intranasally and, seizure severity measures obtained,Behavioral tests, including Elevated Plus-Maze�, open-field, Y-mazewere also performed. Five days following KA treatment, immunohisto-chemical methods were used to assess neuronal degeneration and glialactivation. The production of nitric oxide (NO) and the expression ofnuclear factor kappaB (NF-kB) and AKT in the hippocampus were alsomeasured.Results. ComparedwithWTmice, TNF-a KOmice weremore susceptibileto KA-induced neurotoxicity, as demonstrated by more severe seizures,measurable behavior changes, greater neuronal degeneration in hippo-campus, elevated glial activation and NO production. Additionally, KA-treatment up-regulated the expression of NFkB in TNF-a KO mice to agreater degree than in KA-treated WT mice.Conclusions. We conclude that TNF-a deficiency adversely influencesKA induced neurotoxicity and that TNF-amay play a protective role in KA-induced neurotoxicity via the down-regulation of NFkB signaling pathway.

PRESENCE OF CALBINDIN-D28K RETARDS THE PROCESS OF TANGLEFORMATION IN BASAL FOREBRAIN CHOLINERGIC NEURONS INALZHEIMER’S DISEASE

Saman S. Ahmadian, David Riascos, Melanie Peterson, ChangizGeula. Northwestern University, Feinberg School of Medicine, CognitiveNeurology and Alzheimer’s Disease Center, Chicago, Illinois, USA

Objectives. The reasons for selective vulnerability of specific neuronalpopulations in neurodegenerative disorders remains poorly understood.We have used the basal forebrain cholinergic neurons (BFCN) which areselectively vulnerable in a number of neurodegenerative disorders of theelderly, including Alzheimer’s disease (AD), to investigate the basis of thisvulnerability. The BFCN are exquisitely vulnerable to degeneration andtangle formation in AD. We have established that the majority of the BFCNin the human and non-human primate brain contain the calcium bindingprotein calbinding-D28K (CB) and that a large proportion of these neuronslose their CB in the course of normal aging. Importantly, the BFCN whichdegenerate in AD are those that lack CB. Given that tangle formation is alikely contributor to neuronal degeneration in AD, we investigated therelationship between the presence of CB in the BFCN and the process oftangle formation.Methods. We used pathologically confirmed normal and AD brains ob-tained from the brain bank at our center. One in 24 series of sectionsspanning the entire nucleus basalis (Ch4) component of BFCN, we inves-tigated the presence of neurofibrillary tangles in the CB-positive, whencompared with CB-negative BFCN, using the thioflavin-S stain, and singleas well as double immunohistochemistry with antibodies to CB, tau olig-omer complex-1, which appears early in the process of tangle formation,AT8 and PHF1 which are seen in an intermediate period in tangle forma-tion, and truncated MN422, which appears late in the process of tangle