Olfactory identification in amnestic and non-amnestic mild cognitive impairment and its neuropsychological correlates
Introduction
Olfactory impairment has been demonstrated in Alzheimer's disease (AD) [10], [20], [36], presumably as a consequence of early degeneration of olfactory bulb, olfactory nerve and olfactory cortex situated predominantly in the medial temporal lobe [1], [2], [3]. Among the three major types of olfactory ability (detection, discrimination and identification), the olfactory identification is impaired earlier compared to the olfactory detection in AD patients [50]. So far, most studies with cognitively impaired patients have investigated only olfactory identification, which strongly correlates with olfactory threshold and is easier to test [[9], [11], [12]]. The olfactory identification deficit seems to be specifically linked mainly to the temporal lobe including the amygdala, hippocampus and parahippocampal gyrus, but even anterior temporal damage is sufficient to provoke olfactory identification impairment [21].
Dementia syndrome in AD and in other degenerative disorders is almost always preceded by mild cognitive impairment (MCI) syndrome in which the patients have objective cognitive impairment on neuropsychological examination but do not show substantial deficits in activities of daily living [43], [45].
MCI patients with objective memory impairment are labeled amnestic MCI (aMCI). These patients progress mainly to AD dementia [15], [42], [44], aMCI patients with isolated memory (amnestic) impairment are labeled as the single domain aMCI (aMCIsd), and aMCI patients with an additional impairment in the other cognitive domains beyond memory (e.g., executive impairment, language, visuospatial) are called multiple domain aMCI (aMCImd) [42], [44].
Among aMCI patients, olfactory identification impairment has been demonstrated in a number of studies with a cross sectional design [8], [14], [23], [59]. To our best knowledge only one study also investigated other olfactory modalities beyond olfactory identification in patients with aMCI and it reported impaired olfactory detection and identification. There was also an olfactory discrimination deficit but that was accounted for by an abnormal olfactory threshold [8]. Finally, olfactory impairment in aMCI represents a risk factor for subsequent cognitive decline and conversion to AD dementia, as was demonstrated by some longitudinal studies [6], [53], [54].
MCI patients with normal memory function but with cognitive impairment in non-memory domains (e.g. executive functions, visuospatial functions, language) are classified as non-amnestic MCI (naMCI). Patients with naMCI may convert more frequently to non-AD dementias [42], [44], especially to frontotemporal lobar degeneration (FTLD), Parkinson disease and Lewy body disease (LBD) in which olfactory identification impairment is frequently found [20], [29], [36], [46].
However, there have been only a few studies investigating olfactory functions in naMCI, which report inconsistent results [7], [23], [59]. Considering the evidence of olfactory identification impairment in these non-AD dementias, which are typically preceded by naMCI subtype, we would expect large olfactory impairment in patients with naMCI that may resemble that of patients with aMCI.
Association between olfactory and cognitive impairment in AD and MCI patients is not yet fully understood. The association between memory and olfactory identification performance was demonstrated only in a mixed cohort of healthy elderly and MCI patients and in a mixed cohort of MCI and dementia patients [7], [8], [23], [48], [60]. To our best knowledge the relation between olfactory identification and cognitive performance in MCI, specifically in the amnestic versus non-amnestic MCI subtypes, has not been assessed.
Because of anatomical and functional proximity of brain areas responsible for memory and olfaction (both situated predominantly in the medial temporal lobe), we would expect proportional degree of olfaction and memory impairment in pre-dementia and dementia stages of AD.
To build on previous research, the aim of this study was to:
- 1)
Compare olfactory identification deficit in patients with aMCI vs. naMCI, as well as aMCI and naMCI vs. controls and mild AD.
- 2)
Compare olfactory identification between patients with single vs. multiple domain aMCI.
- 3)
Analyze the association between olfactory identification and cognitive performance in aMCI vs. naMCI.
Section snippets
Subjects
All subjects were recruited from referrals to the Memory Disorders Clinic at Motol Hospital, an affiliate of Charles University in Prague, and signed an informed consent approved by the local ethics committee. They underwent standard protocol which consisted of magnetic resonance imaging, neurological, medical and laboratory evaluation, questionnaires and complex neuropsychological assessment mentioned below. A total of 160 participants were included in the analyses.
The MCI group subjects met
Results
Demographic and neuropsychological characteristics of the diagnostic groups and results of MHST are summarized in Table 1. All four groups differed in age (F [3, 157] = 6.15, p = .001), years of education (F [3, 157] = 4.65, p < . 004), gender (χ2 [3] = 11.53, p < .05), and MMSE (F [3, 157] = 39.0, p < .0001). The subgroups of MCI did not differ in age, years of education, or gender (F [1, 76] < 1.2, p > .27 in all analyses) but they differed in MMSE (F [1, 76] = 6.72, p = .012), whereby AD patients were significantly
Discussion
We assessed olfactory function in a relatively large sample of participants and considered analytically both diagnostic entities (normal, aMCI, naMCI, AD) and neuropsychological assessment scores. Controlling for age and gender, we found that (a) olfactory identification impairment was similar in amnestic and non-amnestic MCI subgroups, (b) aMCImd patients performed worse than those with aMCIsd, and (c) olfactory identification impairment was related mainly to memory and visuospatial function
Acknowledgment
Supported by the FNUSA-ICRC project (no. CZ.1.05/1.1.00/02.0123) from the European Regional Development Fund, by the European Social Fund within the project Young Talent Incubator II (reg. no. CZ.1.07/2.3.00/20.0117), and by the MH CZ — DRO, Motol University Hospital, Prague, Czech Republic 00064203.
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