Neural and behavioral substrates of disorientation in mild cognitive impairment and Alzheimer's disease

Alzheimer's and Dementia: Translational Research and Clinical Interventions - Tập 1 - Trang 37-45 - 2015
Amber Sousa1, Jesus J. Gomar1,2, Terry E. Goldberg1,3
1The Litwin-Zucker Research Center for the Study of Alzheimer's Disease, The Feinstein Institute for Medical Research, Manhasset, NY, USA
2FIDMAG Hermanas Hospitalarias Research Foundation & CIBERSAM, Sant Boi de Llobregat, Spain
3Psychiatry and Molecular Medicine Department, Hofstra North Shore LIJ School of Medicine, Hempstead, NY, USA

Tóm tắt

AbstractBackgroundThe neural and cognitive substrates of measures of orientation as used in clinical trials and examinations have not been comprehensively examined.MethodsWe studied 473 subjects diagnosed with mild cognitive impairment (MCI) and Alzheimer's disease (AD) at baseline in Alzheimer's Disease Neuroimaging Initiative. Regression analyses at baseline were conducted to find significant predictors of orientation score among cognitive, brain morphometry, and glucose metabolism measures. Mixed model longitudinal analysis was performed to examine consequences of orientation on functional decline, and Cox hazard models examined the risk of conversion to AD in the MCI group.ResultsIn MCI and AD subjects, orientation was predicted by poorer neurocognitive performance on immediate and delayed episodic memory and attention and processing speed. Among magnetic resonance imaging measures, orientation was predicted by entorhinal cortex thickness, hippocampal volume, and inferior temporal cortex thickness. Glucose metabolism in both middle‐inferior temporal cortex and hippocampus were also predictive of orientation score. Functioning was significantly lower in disoriented subjects after 4 years of follow‐up, and MCI patients who also were disoriented showed a higher rate of conversion to AD with a hazard ratio of 1.5.ConclusionsOrientation is associated with medial temporal lobe structure, temporal lobe glucose metabolism, and episodic memory function. In MCI individuals orientation was a risk factor for progression to AD, also associated with rapid functional decline and worse prognosis. Thus, orientation may serve as a surrogate for episodic memory in clinical examination. These results have direct implications for the use of orientation in MCI and AD clinical trials including ceiling effects in healthy controls and issues of redundancy with measures of memory, when both are used in composite scores.

Tài liệu tham khảo

10.1002/gps.2282 Hendrix S.B., 2013, Separation of cognitive domains to improve prediction of progression from mild cognitive impairment to Alzheimer's disease, Alzheimers Res Ther, 5, 22, 10.1186/alzrt176 Yew B., 2013, Lost and forgotten? Orientation versus memory in Alzheimer's disease and frontotemporal dementia, J Alzheimers Dis, 33, 473, 10.3233/JAD-2012-120769 10.1176/appi.neuropsych.14.3.311 10.1076/1385-4046(199911)13:04;1-Y;FT495 10.1159/000082034 10.1016/S0167-4943(98)80025-3 10.1098/rstb.2012.0510 10.1098/rstb.2012.0533 Schnider A., 1996, Disorientation in amnesia. A confusion of memory traces, Brain, 119, 1627, 10.1093/brain/119.5.1627 10.1136/jnnp.64.4.552 10.1016/j.jalz.2014.02.002 10.1001/jamaneurol.2014.803 Schneider L.S., 2014, Rethinking the Food and Drug Administration's 2013 guidance on developing drugs for early‐stage Alzheimer's disease, Alzheimers Dement, 10, 247, 10.1016/j.jalz.2013.12.002 10.1111/j.1532-5415.1989.tb05868.x 10.1001/archgenpsychiatry.2011.96 10.1016/j.jalz.2013.11.009 10.1016/0022-3956(75)90026-6 10.1212/WNL.43.11.2412-a 10.1212/WNL.34.7.939 Wechsler D., 1987, Wechsler Memory Scale—revised Rey A., 1964, L'examen clinique en psychologie Goodglass H., 1983, The assessment of aphasia and related disorders Wechsler D., 1981, Wechsler Adult Intelligence Scale‐Revised 10.1016/j.neurobiolaging.2009.07.002 10.1212/01.WNL.0000163856.13524.08 10.1093/geronj/37.3.323 10.1016/S0010-9452(87)80030-8 10.1176/appi.ajp.2012.12030383 Weintraub S., 2009, With or without FUS, it is the anatomy that dictates the dementia phenotype, Brain, 132, 2906, 10.1093/brain/awp286 10.1186/2051-5960-1-65 10.1016/S0079-6123(08)61258-3 10.1007/s004019900166 Alzforum.New frontier: developing outcome measures for pre‐dementia trials.2013 USA 10.1016/j.dadm.2014.11.003
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Alzheimer's and Dementia: Translational Research and Clinical Interventions

Tập 1

37-45

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