Reduced olfactory bulb and tract volume in early Alzheimer's disease—A MRI study

Abstract

Olfactory dysfunction has been reported to occur already in the early stages of Alzheimer's disease (AD) and to increase with disease severity. In neuropathological research, the deposition of neurofibrillary tangles and neuritic plaques in the olfactory bulb and tract (OBT) of AD patients has been consistently demonstrated. We used high-resolution magnetic resonance imaging (MRI) to determine the volume of the OBT in 21 patients with early AD and in 21 healthy comparison subjects. The OBT was manually traced on consecutive coronal slices. When compared to healthy controls, right, left and mean OBT volumes were significantly reduced in patients with AD (p < 0.01). In AD patients, the mean OBT volume was significantly correlated with global cognitive performance as determined by the mini-mental state examination (r = 0.605; p = 0.004). Manual tracing on MRI images revealed OBT atrophy to be present early in the course of AD. Since the respective findings were associated with cognitive impairment, they may contribute to early recognition and diagnosis of the disease.

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.