Interaction Between Odor Identification Deficit and APOE4 Predicts 6-Year Cognitive Decline in Elderly Individuals

Olofsson, Jonas; Larsson, Maria; Roa, Catalina; Wilson, Donald A.; Laukka, Erika J.

doi:10.1007/s10519-019-09980-9

Cited by 21 publications

(16 citation statements)

References 76 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As expected, the percentage of carriers of one or two APOE4 alleles was significantly higher in the aMCI/mAD group than among controls. Harboring APOE4 alleles affects olfaction even in healthy older adults ( 9 ), and the group difference in brain activity could be enhanced by this imbalance. Nevertheless, an APOE4 imbalance will be present in studies of aMCI/AD compared to health elderly due to the importance of APOE4 for AD risk ( 55 ).…”

Section: Discussionmentioning

confidence: 99%

“…As healthy older adults also experience a decline in odor detection and discrimination, but not a similar reduction in OI, OI is considered to separate people with aMCI or AD from older people with intact cognition ( 5 , 7 ). Importantly, OI ability is shown to predict both a later diagnosis of MCI in healthy older adults and conversion from MCI to dementia ( 8 , 9 ). Hence, OI testing can be used as an inexpensive and non-invasive supplement in the clinical evaluation of suspected AD ( 1 , 10 ).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The Human Brain Representation of Odor Identification in Amnestic Mild Cognitive Impairment and Alzheimer's Dementia of Mild Degree

et al. 2021

View full text Add to dashboard Cite

Background: Odor identification (OI) ability is a suggested early biomarker of Alzheimer's disease. In this study, we investigated brain activity within the brain's olfactory network associated with OI in patients with amnestic mild cognitive impairment (aMCI) and mild Alzheimer's dementia (mAD) to uncover the neuronal basis of this impairment.Materials and Methods: Patients with aMCI (n = 11) or mAD (n = 6) and 28 healthy older adults underwent OI functional MRI (fMRI) at 3T, OI, odor discrimination, and cognitive tests and apolipoprotein-e4 (APOE4) genotyping. Eleven patients had cerebrospinal fluid (CSF) analyzed. Those with aMCI were followed for 2 years to examine conversion to dementia.Results: The aMCI/mAD group performed significantly worse on all OI tests and the odor discrimination test compared to controls. The aMCI/mAD group had reduced activation in the right anterior piriform cortex compared to the controls during OI fMRI [Gaussian random field (GRF) corrected cluster threshold, p < 0.05]. This group difference remained after correcting for age, sex education, and brain parenchymal fraction. This difference in piriform activity was driven primarily by differences in odor discrimination ability and to a lesser extent by OI ability. There was no group by odor discrimination/identification score interaction on brain activity. Across both groups, only odor discrimination score was significantly associated with brain activity located to the right piriform cortex. Brain activity during OI was not associated with Mini Mental Status Examination scores. At the group level, the aMCI/mAD group activated only the anterior insula, while the control group had significant activation within all regions of the olfactory network during OI fMRI. There was no association between brain activity during OI fMRI and total beta-amyloid levels in the CSF in the aMCI/mAD group.Conclusion: The OI impairment in aMCI/mAD patients is associated with significantly reduced activity in the piriform cortex compared to controls. Activation of downstream regions within the olfactory network is also significantly affected in the aMCI/mAD group, except the anterior insula, which is impinged late in the course of Alzheimer's disease. OI tests thus reflect Alzheimer's disease pathology in olfactory brain structures.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Human Brain Representation of Odor Identification in Amnestic Mild Cognitive Impairment and Alzheimer's Dementia of Mild Degree

et al. 2021

View full text Add to dashboard Cite

show abstract

“…In relation to this, however, there have been some interesting findings. Several studies have noted that olfactory impairment has greater salience – is a stronger predictor of decline – among individuals who carry the APOE 4 allele (Graves et al, 1999 ; Olofsson et al, 2020 ). One way to interpret this finding is that the presence of a known strong risk factor for AD (i.e., APOE ε4) increases the likelihood that olfactory impairment, when present, has a neurodegenerative (central not peripheral) basis.…”

Section: Discussionmentioning

confidence: 99%

Olfaction and Executive Cognitive Performance: A Systematic Review

Ramaswamy

Schofield

2022

Front. Psychol.

View full text Add to dashboard Cite

Objective tests of olfaction are widely available to aid in the assessment of olfaction. Their clearest role is in the characterization of olfactory changes, either reported by or suspected in a patient. There is a rapidly growing literature concerned with the association of olfactory changes with certain neuropsychiatric conditions and the use of olfactory testing to supplement conventional assessments in clinical and research practice is evolving. Neural pathways important for olfactory processing overlap extensively with pathways important for cognitive functioning, and especially those important for executive functioning, many of which are concentrated in the frontal lobes. Previous work has identified associations between performance on certain olfactory tests (most frequently olfactory identification) and executive functioning and behavioral measures (e.g. of impulsivity). More recently, similar associations have also been identified in non-clinical samples, raising new questions as to the utility of olfactory test scores as proxy measures for non-olfactory phenomena. In this systemic review, we sought to identify studies, both clinical and non-clinical, that investigated the associations of olfaction with performance on tasks sensitive to frontal lobe functioning. Our search criteria led to the identification of 70 studies published in English. We examined in detail and tabulated the data from these studies, highlighted each study's key findings, and critically evaluated these studies. We use the results of this review to reflect on some of the current and future challenges concerning the use of olfactory testing in clinical neuropsychiatric practice and research and speculate on the potential benefits of administering phonemic fluency in combination with olfactory testing to enhance its predictive value.

show abstract

“…Here, we use a large dataset ( Larsson et al 2016 ) with 2,476 participants in the age range of 60–100 years to investigate how odor identification is related to perceptual odor features. In previous research, this dataset has been used to understand risk factors for olfactory dysfunction ( Palmquist et al 2020 ), and the relationship between olfactory and cognitive dysfunction ( Olofsson et al 2020 ), using aggregated odor identification scores. The aim of the present study was to understand odor identification performance using odor item information as a function of perceptual dimensions.…”

Section: Introductionmentioning

confidence: 99%

Perceptual odor qualities predict successful odor identification in old age

et al. 2022

Self Cite

View full text Add to dashboard Cite

Odor identification is a common assessment of olfaction, and it is affected in a large number of diseases. Identification abilities decline with age, but little is known about whether there are perceptual odor features that can be used to predict identification. Here, we analyzed data from a large, population-based sample of 2,479 adults, aged 60 years or above, from the Swedish National study on Aging and Care in Kungsholmen. Participants performed both free and cued odor identification tests. In a separate experiment, we assessed perceived pleasantness, familiarity, intensity, and edibility of all odors in the first sample, and examined how odor identification performance is associated with these variables. The analysis showed that high-intensity odors are easier to identify than low-intensity odors overall, but also that they are more susceptible to the negative repercussions of old age. This result indicates that sensory decline is a major aspect of age-dependent odor identification impairment, and suggests a framework where identification likelihood is proportional to the perceived intensity of the odor. Additional analyses further showed that high-performing individuals can discriminate target odors from distractors along the pleasantness and edibility dimensions and that unpleasant and inedible odors show smaller age-related differences in identification. Altogether, these results may guide further development and optimization of brief and efficient odor identification tests as well as influence the design of odorous products targeted toward older consumers.

show abstract

Interaction Between Odor Identification Deficit and APOE4 Predicts 6-Year Cognitive Decline in Elderly Individuals

Cited by 21 publications

References 76 publications

The Human Brain Representation of Odor Identification in Amnestic Mild Cognitive Impairment and Alzheimer's Dementia of Mild Degree

The Human Brain Representation of Odor Identification in Amnestic Mild Cognitive Impairment and Alzheimer's Dementia of Mild Degree

Olfaction and Executive Cognitive Performance: A Systematic Review

Perceptual odor qualities predict successful odor identification in old age

Contact Info

Product

Resources

About