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Human olfaction: Associations with longitudinal assessment of episodic memory, dementia, and mortality risk
Stockholm University, Faculty of Social Sciences, Department of Psychology, Perception and psychophysics.
2018 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

A declining sense of smell is a common feature in older age. Above and beyond diminished smelling capacity due to normal processes of human aging, impairments in olfactory function have also been linked to numerous ill-health related outcomes, such as cognitive dysfunctions, dementia pathology and even an increased risk of death. Based on population-based data from the Swedish Betula Prospective Cohort Study, the aim of this thesis was to further our understanding regarding the role of olfaction in long-term memory decline, dementia, and mortality. Furthermore, this thesis investigated the predictive utility of self-reported olfactory dysfunction for assessing the risk of conversion to later dementia and to mortality, as well as the predictive utility of long-term subjective olfactory decline for an actual long-term decline in odor function. Study I explored associations of olfactory deficits with memory decline and found that impairments in an odor identification test were related to an ongoing and long-term decline in episodic memory only in carriers of the e4 allele of the Apolipoprotein E, a genetic risk factor for Alzheimer’s disease. Study II investigated the predictive utility of olfactory ability for conversion to common forms of dementia in participants with intact baseline cognition during a follow-up time-span of 10 years. The results showed that lower odor identification scores, as well as subjectively assessed odor impairment, were associated with an increased risk for dementia conversion, and that the effects of objective and subjective odor function were cumulative. Study III investigated whether olfactory ability could predict mortality and showed that lower odor identification scores, as well as subjective odor impairments, were associated with an elevated risk of death within a follow-up time-span of approximately 10 years. Crucially, this effect could not be explained by dementia conversion prior to death. Study IV showed that a subjectively assessed long-term and ongoing olfactory decline was predictive of an objectively assessed long-term and ongoing decline in odor function. Subjective olfactory impairments might thus be indicative of an actual olfactory decline in older adults. Overall, the findings of this thesis indicate that sense of smell is closely related to processes of memory decline and dementia as well as mortality in older adults. Furthermore, the results of these investigations shed a new light on the role of subjectively experienced olfactory decline, which might reflect an actual intra-individual change in olfactory ability in older adults.

Place, publisher, year, edition, pages
Stockholm: Department of Psychology, Stockholm University , 2018. , p. 147
Keywords [en]
olfaction, odor identification, self-assessments, aging, episodic memory, ApoE, dementia, Alzheimer’s disease, vascular dementia, mortality, cohort study, population-based.
National Category
Psychology
Research subject
Psychology
Identifiers
URN: urn:nbn:se:su:diva-154414ISBN: 978-91-7797-220-4 (print)ISBN: 978-91-7797-221-1 (electronic)OAI: oai:DiVA.org:su-154414DiVA, id: diva2:1198320
Public defence
2018-06-08, David Magnussonsalen (U31), Frescati Hagväg 8, Stockholm, 09:00 (English)
Opponent
Supervisors
Note

At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 4: Submitted.

Available from: 2018-05-16 Created: 2018-04-17 Last updated: 2019-01-21Bibliographically approved
List of papers
1. Long-term episodic memory decline is associated with olfactory deficits only in carriers of ApoE-є4
Open this publication in new window or tab >>Long-term episodic memory decline is associated with olfactory deficits only in carriers of ApoE-є4
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2016 (English)In: Neuropsychologia, ISSN 0028-3932, E-ISSN 1873-3514, Vol. 85, p. 1-9Article in journal (Refereed) Published
Abstract [en]

The ɛ4 allele of the Apolipoprotein E gene is a genetic risk factor for late-onset dementia of the Alzheimers' type (DAT), which is characterized by loss of both episodic memoryand olfactory functions. Little is known about the possible role of ɛ4 in the association between ongoing episodic memory decline and olfactory deficits in the general population, but such information is relevant in determining the relevance of olfaction as a marker of DAT risk. The present study was based on a large, population-based sample (n=1087, aged 45–90 years, of which 324 were ɛ4-carriers). Episodic memory change rates were established using data collected every 5 years for a 10–20 year interval leading up to an olfactory assessment using the Scandinavian Odor Identification Test at the last wave of data collection. Participants were classified according to whether or not their episodic memory ability declined more rapidly than the age-typical norm (by >1SD). Our main result is that only in ɛ4-carriers was episodic memory decline associated with odor identification impairment. In individuals without ɛ4, odor identification was unrelated to episodic memory decline status. Follow-up analyses indicated that this moderation by ɛ4 was due to the olfactory nature of the identification test, and that the effect was not caused by 63 individuals with dementia. Our results suggest that the ɛ4 determines the functional association between ongoing episodic memory decline and olfaction. These findings are consistent with the notion that ɛ4-carriers with DAT, compared to non-carriers, display a cortical atrophy pattern that is more focused on mediotemporal lobe regions supporting olfactory and episodic memory functions. Olfactory and memory assessments might provide complementary information on mediotemporal atrophy prior to clinical dementia onset, but the ɛ4 should be considered when using olfactory assessment as an early-stage indicator.

Keywords
dementia, Alzheimer disease, olfactory perception, memory, aging, mild cognitive impairment
National Category
Psychology
Research subject
Psychology
Identifiers
urn:nbn:se:su:diva-130568 (URN)10.1016/j.neuropsychologia.2016.03.004 (DOI)000376546400001 ()
Available from: 2016-05-26 Created: 2016-05-26 Last updated: 2018-04-18Bibliographically approved
2. Olfactory Impairment and Subjective Olfactory Complaints Independently Predict Conversion to Dementia: A Longitudinal, Population-Based Study
Open this publication in new window or tab >>Olfactory Impairment and Subjective Olfactory Complaints Independently Predict Conversion to Dementia: A Longitudinal, Population-Based Study
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2014 (English)In: Journal of the International Neuropsychological Society, ISSN 1355-6177, E-ISSN 1469-7661, Vol. 20, no 2, p. 209-217Article in journal (Refereed) Published
Abstract [en]

We examined whether conversion to dementia can be predicted by self-reported olfactory impairment and/or by an inability to identify odors. Common forms of dementia involve an impaired sense of smell, and poor olfactory performance predicts cognitive decline among the elderly. We followed a sample of 1529 participants, who were within a normal range of overall cognitive function at baseline, over a 10-year period during which 159 were classified as having a dementia disorder. Dementia conversion was predicted from demographic variables, Mini-Mental State Examination score, and olfactory assessments. Self-reported olfactory impairment emerged as an independent predictor of dementia. After adjusting for effects of other predictors, individuals who rated their olfactory sensitivity as worse than normal were more likely to convert to dementia than those who reported normal olfactory sensitivity (odds ratio [OR] = 2.17; 95% confidence interval [CI] [1.40, 3.37]). Additionally, low scores on an odor identification test also predicted conversion to dementia (OR per 1 point increase = 0.89; 95% CI [0.81, 0.98]), but these two effects were additive. We suggest that assessing subjective olfactory complaints might supplement other assessments when evaluating the risk of conversion to dementia. Future studies should investigate which combination of olfactory assessments is most useful in predicting dementia conversion. (JINS, 2014, 20, 1-9)

Keywords
Alzheimer type dementia, Awareness, Olfaction, Smell disorder, Memory, Vascular dementia
National Category
Psychology Neurosciences
Identifiers
urn:nbn:se:su:diva-102990 (URN)10.1017/S1355617713001409 (DOI)000332448700010 ()
Note

AuthorCount:6;

Available from: 2014-04-25 Created: 2014-04-25 Last updated: 2018-04-17Bibliographically approved
3. Smell Loss Predicts Mortality Risk Regardless of Dementia Conversion
Open this publication in new window or tab >>Smell Loss Predicts Mortality Risk Regardless of Dementia Conversion
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2017 (English)In: Journal of The American Geriatrics Society, ISSN 0002-8614, E-ISSN 1532-5415, Vol. 65, no 6, p. 1238-1243Article in journal (Refereed) Published
Abstract [en]

Objectives

To determine whether dementia could explain the association between poor olfactory performance and mortality risk within a decade-long follow-up period.

Design

Prospective cohort study.

Setting

Betula Study, Umeå, Sweden.

Participants

A population-based sample of adult participants without dementia at baseline aged 40 to 90 (N = 1,774).

Measurements

Olfactory performance using the Scandinavian Odor-Identification Test (SOIT) and self-reported olfactory function; several social, cognitive, and medical risk factors at baseline; and incident dementia during the following decade.

Results

Within the 10-year follow-up, 411 of 1,774 (23.2%) participants had died. In a Cox model, the association between higher SOIT score and lower mortality was significant (hazard ratio (HR) = 0.74 per point interval, 95% confidence interval (CI) = 0.71-0.77, P < .001). The effect was attenuated, but remained significant, after controlling for age, sex, education, and health-related and cognitive variables (HR = 0.92, 95% CI = 0.87-0.97, P = .001). The association between SOIT score and mortality was retained after controlling for dementia conversion before death (HR = 0.92, 95% CI = 0.87-0.97, P = .001). Similar results were obtained for self-reported olfactory dysfunction.

Conclusion

Poor odor identification and poor self-reported olfactory function are associated with greater likelihood of future mortality. Dementia does not attenuate the association between olfactory loss and mortality, suggesting that olfactory loss might mark deteriorating health, irrespective of dementia.

Keywords
olfaction disorders, smell, Alzheimer disease, mortality, longitudinal studies
National Category
Psychology Geriatrics
Research subject
Psychology
Identifiers
urn:nbn:se:su:diva-145242 (URN)10.1111/jgs.14770 (DOI)000403894000021 ()28326534 (PubMedID)
Available from: 2017-07-27 Created: 2017-07-27 Last updated: 2018-04-18Bibliographically approved
4. Subjective olfactory loss corresponds to long-term odor identification decline in older adults
Open this publication in new window or tab >>Subjective olfactory loss corresponds to long-term odor identification decline in older adults
(English)In: Article in journal (Refereed) Submitted
National Category
Psychology
Research subject
Psychology
Identifiers
urn:nbn:se:su:diva-155333 (URN)
Available from: 2018-04-18 Created: 2018-04-18 Last updated: 2018-04-18Bibliographically approved

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