Current Alzheimer Research, 2011, 8, 689-698 689 1567-2050/11 $58.00+.00 © 2011 Bentham Science Publishers Follow-Up Study of Olfactory Deficits, Cognitive Functions, and Volume Loss of Medial Temporal Lobe Structures in Patients with Mild Cognitive Impairment W. Lojkowska 1,* , B. Sawicka 1 , M. Gugala 1 , H. Sienkiewicz-Jarosz 1 , A. Bochynska 1 , A. Scinska 2 , A. Korkosz 2 , E. Lojek 3 and D. Ryglewicz 1 1 1 st Department of Neurology and 2 Department of Pharmacology, Institute of Psychiatry and Neurology, Warsaw, Po- land; 3 Warsaw University, Poland Abstract: Background: At 3 years after diagnosis, the risk of Alzheimer disease (AD) for patients with mild cognitive impairment (MCI) is estimated to be 18% to 30%. To improve treatment of patients at high dementia risk there is a need for a better prediction of the risk for transition from MCI to AD. Olfactory deficits are a hypothetical predictor of conver- sion form MCI to AD. Furthermore, several studies point at volumetric reduction of medial temporal lobe structures as predictors of conversion form MCI to AD. The primary aim of this study was to evaluate whether investigations of odor deficits in MCI combined with neuropsychological tests and MRI examinations can improve prediction of the develop- ment of dementia. Methods: Changes in olfactory functions, cognitive functions, and volume of medial temporal lobe structures (hippocampus, parahippocampal gyrus, and amygdala) were evaluated in a 24-month follow-up study in 49 MCI patients and 33 controls. Results: In the MCI group, a prediction of strong cognitive functions deterioration based on poor performance in Olfactory Identification tests shows sensitivity of 57% and specificity of 88%. The test based on cognitive functions only shows a sensitivity of 44%, and 89%, respectively. Combined tests having a criteria of poor ol- factory identification performance AND poor results of neuropsychological tests showed a sensitivity of 100% and speci- ficity of 84%. Furthermore, correlation was found between the results of Olfactory Identification tests at baseline and de- terioration of cognitive functions at follow up. Odor identification threshold did not appear to be a dementia predictor. A correlation of progress of cognitive function deterioration, odor identification deterioration, and decrease of volume of the hippocampus was also observed. Conclusions: Prediction of MCI to dementia conversion can be improved by supple- menting the neuropsychological tests with odor identification tests. A follow up study of hippocampus volume reduction, OI performance and cognitive functions deterioration will further increase prediction accuracy. Keywords: Mild cognitive impairment, olfaction, odor, MRI, hippocampus, amygdala, parahippocampal gyrus, cognitive functions. 1. INTRODUCTION Mild cognitive impairment (MCI) refers to a transitional state between normal aging and mild dementia [1, 2]. Con- siderable research efforts concern improving the accuracy of MCI diagnosis and predicting conversion of MCI to Alz- heimer’s disease (AD) or other dementias [2]. The risk of AD for patients diagnosed with MCI is 18% to 30% at 3 years after diagnosis [3]. MCI patients can also show dete- rioration in cognitive functions that are seen with normal aging. Improved diagnostic methods are needed therefore to predict conversion of MCI to AD. A promising research di- rection is the assessment of olfactory function in participants with MCI as a predictor for dementia. There is extensive research to assess olfactory performance, i.e. odor identifica- tion (OI) and odor detection threshold (ODT), as predictors for AD [4-8] and in MCI diagnosis [9-13]. In a follow up study, Wilson et al. [10] showed that odor identification im- pairment is related to increased risk of incident MCI among older persons. Schubert et al. [14] reported that OI is useful in the identification of patients at risk for cognitive decline in *Address correspondence to this author at the 1 st Department of Neurology, Institute of Psychiatry and Neurology, Warsaw, Poland; Tel: +48-22-458- 2548; Fax: +48-22-458-2566; E-mail: wlojkowska@poczta.onet.pl high-risk settings, but not in the general population. Westervelt et al. [10] studied correlations between the neu- ropsychological test results and odor identification in older persons. They found strong correlations between odor identi- fication ability and tests of language, most aspects of mem- ory, and general cognitive functioning. They suggest that olfactory measures are underutilized in both neurologic and neuropsychologic exams, and may offer unique information about brain functioning. Concerning the prediction of AD, Djordjevic et al. [13] found that olfactory deficits occur be- fore full clinical symptoms of AD. In a recent follow up study of MCI participants, Devanand et al. [15] reported that a combination of five predictors improved prediction of MCI conversion to AD: Pfeffer Functional Activities Question- naire – informant report on functioning, University of Penn- sylvania Smell Identification Test, Selective Reminding Test, MRI hippocampal volume, and MRI entorhinal cortex volume. The authors suggested the need for future investiga- tions of such correlations to verify these findings in an inde- pendent study. In another paper by Devanand et al. [16], the authors reported the need for additional longitudinal studies to determine the predictive utility of OI in assessing decline from no MCI to MCI and from MCI to AD.