Olfactory identification in amnestic and non-amnestic mild cognitive impairment and its neuropsychological correlates

https://doi.org/10.1016/j.jns.2015.01.014Get rights and content

Highlights

  • No difference in odor identification between amnestic and non-amnestic MCI was found.

  • Relation of olfaction and cognition in MCI subtypes was examined.

  • Cognitive performance correlated with odor identification in aMCI not in naMCI.

Abstract

Background

Olfactory identification impairment in amnestic mild cognitive impairment (aMCI) patients is well documented and considered to be caused by underlying Alzheimer's disease (AD) pathology, contrasting with less clear evidence in non-amnestic MCI (naMCI). The aim was to (a) compare the degree of olfactory identification dysfunction in aMCI, naMCI, controls and mild AD dementia and (b) assess the relation between olfactory identification and cognitive performance in aMCI compared to naMCI.

Methods

75 patients with aMCI and 32 with naMCI, 26 patients with mild AD and 27 controls underwent the multiple choice olfactory identification Motol Hospital Smell Test with 18 different odors together with a comprehensive neuropsychological examination.

Results

Controlling for age and gender, patients with aMCI and naMCI did not differ significantly in olfactory identification and both performed significantly worse than controls (p < 0.001), albeit also better than patients with mild AD (p < .001). In the aMCI group, higher scores on MMSE, verbal and non-verbal memory and visuospatial tests were significantly related to better olfactory identification ability. Conversely, no cognitive measure was significantly related to olfactory performance in naMCI.

Conclusion

Olfactory identification is similarly impaired in aMCI and naMCI. Olfactory impairment is proportional to cognitive impairment in aMCI but not in naMCI.

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.

References (62)

  • J.A. Yesavage et al.

    Development and validation of a geriatric depression screening scale: a preliminary report

    J Psychiatr Res

    (1983)
  • J. Attems et al.

    Olfactory involvement in aging and Alzheimer's disease: an autopsy study

    J Alzheimers Dis

    (2005)
  • H. Braak et al.

    Neuropathological stageing of Alzheimer-related changes

    Acta Neuropathol

    (1991)
  • A. Busse et al.

    Mild cognitive impairment: long-term course of four clinical subtypes

    Neurology

    (2006)
  • J.A. Cohen

    Statistical power analysis for the behavioral sciences

    (1988)
  • D.P. Devanand et al.

    Olfactory deficits in patients with mild cognitive impairment predict Alzheimer's disease at follow-up

    Am J Psychiatry

    (2000)
  • R.L. Doty

    Office procedures for quantitative assessment of olfactory function

    Am J Rhinol

    (2007)
  • R.L. Doty et al.

    University of Pennsylvania Smell Identification Test: a rapid quantitative olfactory function test for the clinic

    Laryngoscope

    (1984)
  • K. Duff et al.

    The pocket smell test successfully discriminating probable Alzheimer's dementia from vascular dementia and major depression

    J Neuropsychiatry Clin Neurosci

    (2002)
  • A. Eibenstein et al.

    Olfactory screening test in mild cognitive impairment

    Neurol Sci

    (2005)
  • S.T. Farias et al.

    Progression of mild cognitive impairment to dementia in clinic-vs community-based cohorts

    Arch Neurol

    (2009)
  • F. Fazekas et al.

    MR signal abnormalities at 1.5 T in Alzheimer's dementia and normal aging

    AJR Am J Roentgenol

    (1987)
  • A.J. Gray et al.

    Olfactory identification is impaired in clinic-based patients with vascular dementia and senile dementia of Alzheimer type

    Int J Geriatr Psychiatry

    (2001)
  • E. Grober et al.

    Genuine memory deficits in dementia

    Dev Neuropsychol

    (1987)
  • C. Hawkes

    Olfaction in neurodegenerative disorder

    Mov Disord

    (2003)
  • M. Jones-Gotman et al.

    Contribution of medial versus lateral temporal-lobe structures to human odour identification

    Brain

    (1997)
  • S. Jungwirth et al.

    The validity of amnestic MCI and non-amnestic MCI at age 75 in the prediction of Alzheimer's dementia and vascular dementia

    Int Psychogeriatr

    (2012)
  • J. Lehrner et al.

    Odor identification and self-reported olfactory functioning in patients with subtypes of mild cognitive impairment

    Clin Neuropsychol

    (2009)
  • M.D. Lezak et al.

    Neuropsychological assessment

    (2004)
  • P. Liberini et al.

    Olfactory dysfunction in dementia associated with Lewy bodies

    Parkinsonism Relat Disord

    (1999)
  • A.S. Loonstra et al.

    COWAT metanorms across age, education, and gender

    Appl Neuropsychol

    (2001)
  • Cited by (35)

    • Sleep, neuronal hyperexcitability, inflammation and neurodegeneration: Does early chronic short sleep trigger and is it the key to overcoming Alzheimer's disease?

      2021, Neuroscience and Biobehavioral Reviews
      Citation Excerpt :

      Disorders of odour detection thresholds, discrimination ability, and recognition are among the first symptoms of AD compared to controls of the same age (Ferreyra-Moyano and Barragan, 1989; Mesholam et al., 1998; Nordin and Murphy, 1998). The presence of underlying neuropathology involves critical areas for the processing of olfactory information, as brain structures closely related to the olfactory system correspondingly demonstrate significant early histopathology in MCI (Cross et al., 2013; Murphy et al., 2003; Vyhnalek et al., 2015), suggesting that altered olfaction is a diagnostic parameter of cognitive decline in MCI and a marker of conversion to AD (Attems et al., 2014; Bathini et al., 2019; Gray et al., 2001; Murphy, 2019; Schofield et al., 2014). Interestingly, the OB is a major efferent target of LC, and about 40 % of LC neurons project into different layers of OB as in rodents (McLean et al., 1989; Shipley et al., 1995), and that norepinephrine is strongly involved in olfactory perception and memory, while the loss of noradrenergic neurons in the LC exacerbated olfactory memory in a mouse model of amyloidosis (Heneka et al., 2010; Jardanhazi-Kurutz et al., 2010) (example Table 6).

    View all citing articles on Scopus
    View full text