Olfactory Dysfunction And Hippocampal Structural Changes In Patients With Amnestic Cognitive Impairment

Background:Alzheimer's disease ?AD? is the most common form of clinical dementia which is characterized by progressive cognitive decline and dysfunction of multiple cognitive domains. The pathological hallmarks of AD, such as abnormal accumulation of extracellular beta-amyloid ?AP? plaques and intracellular neurofibrillary tangles ?NFTs?, were observed and detected in cerebral cortex and certain memory-related subcortical regions. Furthermore, such pathological changes were also observed in olfactory related cortex and regions, which resulted in clinical olfactory dysfunction. Previous researches suggested that olfactory decline detected in patients with cognitive impairment could be a potential biomarker for AD pathology, which indicated that a battery of olfactory tests could be a useful tool for clinical cognitive assessment and early diagnosis of AD.Objectives:To determine the characteristic of olfactory dysfunction in patients with cognitive impairment and to evaluate the use of OLFACT-CTM by hippocampal volumetry analysis based on local population.Methods:From June 2014 to January 2015, seventy-five patients with memory complaints from Neurology Clinic of Drum Tower Hospital were recruited into this study. Thirty-one subjects and seven subjects were diagnosed with mild cognitive impairment ?MCI? and probable AD, respectively. Twenty-one subjects were considered as cognitively normal ?CN?. Fourteen subjects were consider as Parkinson's disease and were excluded in this study. Two subjects with nausea of the odors were also excluded. Olfactory test battery which included one trial of threshold test, two trials of identification tests and one trial of memory test were performed by the OLFACT-CTM ?Osmic Enterprises, Inc., Cincinnati, Ohio, United States?. Imaging acquisition was performed by the Philips 3.0 T TX MRI scanner ?Philips Medical Systems, Eindhoven, Netherlands? with a 8-channel phased coil. Segmentation and volumetry analysis of Hippocampus and hippocampal subfields were performed by the FreeSurfer?5.3.0? to investigate the correlation between olfactory tests results and hippocampal atrophy.Results:Significant differences of olfactory threshold and odor identification scores were observed between the CN, MCI and AD subjects. Increased olfactory threshold and lower identification scores were correlated with progressive cognitive decline. However, no significant difference of olfactory memory skill were observed between the groups. Partial correlation analysis indicated that olfactory threshold was correlated with age ?p=0.011? after controlling for cognitive performances, whereas odor identification scores were correlated with both aging ?p=0.001? and cognitive decline ?p=0.000?. Recognition performances of old odors were correlated with both aging ?p=0.037? and cognitive decline ?p=0.020?. However, no such correlations were observed in the performances of identifying new odors. Volumetry analysis detected significant differences of bilateral hippocampi and hippocampal subfields such as CA1, CA2₃, CA4_DG, subiculum and presubiculum between the cognitive impaired and cognitive normal subjects. Furthermore, significant correlation between odor identification and atrophy of the right hippocampal CA1, CA23, and CA4DG were observed between the groups, which suggest the potential use of olfactory identification test as a additional cognitive assessment tool.Conclusions:Olfactory threshold was correlated with aging while the correlation between olfactory memory and cognitive decline remain unclear. Olfactory identification was correlated with both aging, cognitive decline and structural changes in hippocampal subfields, which indicated the use of odor identification test for clinical cognitive assessment.