Brief communicationReduced olfactory bulb and tract volume in early Alzheimer's disease—A MRI study
Introduction
Alzheimer's disease (AD) is the most frequent dementia beyond the age of 65 years, affecting an eminent and increasing part of the population. Neuropathologically, AD is characterized by neuronal loss and deposition of neurofibrillary tangles (NFTs) and amyloid plaques in the brain. Post-mortem studies demonstrated that three main stages can be differentiated during the clinical course of AD (Braak stages, Braak et al., 1993), with parahippocampal regions the earliest to be affected (Braak stages 1 and 2), before the pathological alterations spread into additional structures of the medial temporal lobe/limbic system (Braak stages 3 and 4) and then encroach major parts of the temporal, parietal, and frontal cortical areas (Braak stages 5 and 6).
Limbic structures, early involved in the course of the AD, have olfactory connections. Olfactory dysfunction in AD has consistently been reported by a number of independent research groups (Larsson et al., 1999, Mesholam et al., 1998, Murphy et al., 1990, Nordin et al., 1997). Following the results of neuropathological studies (Attems and Jellinger, 2006, Kovacs et al., 1999, Tsuboi et al., 2003) impaired olfaction in AD seems to refer to the deposition of amyloid plaques and neurofibrillary tangles in the olfactory bulb which constitutes the first synaptic relay in the olfactory pathway (e.g., Nieuwenhuys et al., 1988).
The majority of magnetic resonance imaging (MRI) studies investigating morphological alterations in early AD revealed – according to the above mentioned main stages of the disease – predominantly the substructures of the medial temporal lobe to undergo atrophic processes (for review see Chetelat and Baron, 2003). Interestingly, MRI studies on potential structural changes of the olfactory bulb and tract (OBT) in AD have not been performed yet, although this structure can be reliably delineated on adequate MR images (Abolmaali et al., 2002, Rombaux et al., 2006, Turetsky et al., 2003, Yousem et al., 1998).
In the present study, we therefore ascertained the volumes of the OBT in patients with mild AD and in healthy controls by using high-resolution MRI under the hypothesis that AD patients would show significantly lower OBT volumes than healthy comparison subjects, referring to an early accumulation of NFTs and amyloid plaques in this area.
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Subjects
Twenty-one patients with mild AD (according to the NINCDS-ADRDA criteria (McKhann et al., 1984), with all patients fulfilling the criteria of probable AD) and 21 healthy controls were included in this study. Both patients and controls were consecutively recruited through the section of geriatric psychiatry at the University of Heidelberg, Germany. The clinical evaluation of all subjects included ascertainment of personal and family history as well as physical, neurological and
Results
According to statistical analysis there were no significant differences with respect to age, gender distribution, and level of school education. As expected, the mean MMSE score in AD patients was significantly lower when compared to controls (p < 0.001). Subject demographics and volumetric measures are reported in Table 1. Student's two-tailed t-test yielded no significant difference for the intracranial volume, but for the right (p = 0.001), left (p = 0.003) and mean (p = 0.001) OBT volume with lower
Discussion
Our study yielded two major findings: (i) in patients with mild AD, the OBT volume was significantly reduced when compared to healthy controls and (ii) in the patient's group, the OBT volume was significantly correlated with global cognitive performance as determined by the MMSE.
Recently, neuropathological research described the OBT to undergo degenerative alterations in AD; in their study on 15 autopsy AD cases and 15 healthy controls, Kovacs et al. (1999) detected NFT pathology in the OBT in
Disclosure statement
No conflicts of interest to declare by any of the authors.
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