MRI-Derived Atrophy of the Olfactory Bulb and Tract in Mild Cognitive Impairment and Alzheimer's Disease

Abstract

There is increasing histopathological evidence that the olfactory bulb and tract (OBT) is a primary focus of neurodegenerative changes in Alzheimer's disease (AD). Correspondingly, high-resolution magnetic resonance imaging revealed significant atrophy of the OBT in manifest AD. Whether these alterations are already present in mild cognitive impairment, the assumed preclinical stage of AD, has not been investigated yet. OBT volumes were assessed by manual tracing in 29 patients with mild cognitive impairment, 27 patients with probable AD, and 30 healthy controls. In a second step, voxel based morphometry was used to investigate the potential association between OBT atrophy and morphological changes in other brain regions. Patients had significantly lower OBT volumes when compared to controls, with atrophy being most prominent in the AD group. In addition, OBT atrophy was associated with a decreased medial temporal lobe (MTL) gray matter density bilaterally. Our findings indicate that neurodegeneration in OBT and MTL regions is linked and suggest that OBT volume might be a surrogate marker in AD.

Decisive role of Reelin signaling during early stages of Alzheimer’s disease

“…Importantly, ApoE ε4 carriers display higher tau pathology in the anterior olfactory nucleus (AON) in comparison to the ε4 negative individuals (Tsuboi et al, 2003). Finally, an MRI study demonstrated that pronounced olfactory bulb and fiber tract atrophy, a specific hallmark of AD (Mundinano et al, 2011), is present already very early in MCI patients (Thomann et al, 2009). Along the same line, it was shown that dystrophic neurites in the olfactory epithelium show high accumulations of paired helical filaments (PHFs; precursor elements of neurofibrillary tangles) and intracellular APP/Aβ in AD patients (Arnold et al, 2010).…”

The Predictive Role of Hyposmia in Alzheimer's Disease

“…Compared to the olfactory tests the role of olfactory event-related potentials (OERPs) is considered useful in the diagnosis of AD (Morgan&Murphy, 2002). The results of olfactory tests are supported by functional imaging techniques (CT, MRI, PET) which show a reduced activation of the central olfactory structures (Wang et al, 2010), mainly on the right side (Kareken et al, 2001) and an atrophy of hippocampus (Jack et al, 1992;Yousem et al, 2001) and olfactory bulb (Thomann et al, 2009). Murphy et al (Murphy et al, 2003) studied olfactory function (odor threshold and odor identification) and volumetric MRI measures of mesial temporal areas (hippocampus, the parahippocampal gyrus and the amygdala) in patients with probable AD.…”

Caffeine blocks cholesterol-enriched diet induced AD-like pathology in rabbits

“…Thus, altered cholesterol homeotasis could contribute to the development of olfactory dysfunction in sporadic AD. Pathologically, oxidative damage, the presence of Aβ plaque, and accumulation of phosphorylated tau as neurofilrillary tangles all have been documented in olfactory epithelium and olfactory bulbs of AD patients [44][45][46][47][48][49][50][51]. Previously we showed in olfactory bulb from cholesterol-fed rabbits that elevated levels of circulating cholesterol disrupted the blood-brain barrier [16], increased accumulations of cholesterol in endolysosomes of neurons in olfactory bulb originated from peripheral sources, and contributed to the development of AD-like pathology including synaptic loss, elevated Aβ production, and increased tau phosphorylation [7].…”