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Eek, T., Bolton, T. A. W., Dizdar, N., Larsson, M., Lundin, F. & Georgiopoulos, C. (2025). Impaired odor recognition memory in Parkinson’s disease linked to absent functional hippocampal asymmetry. npj Parkinson's Disease, 11, Article ID 56.
Open this publication in new window or tab >>Impaired odor recognition memory in Parkinson’s disease linked to absent functional hippocampal asymmetry
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2025 (English)In: npj Parkinson's Disease, E-ISSN 2373-8057, Vol. 11, article id 56Article in journal (Refereed) Published
Abstract [en]

Odor recognition memory (ORM) combines olfaction and episodic memory, both linked to dementia and impaired in Parkinson’s Disease (PD). Measuring ORM may indicate early PD dementia and aid in selecting device-aided Parkinson therapy. This study investigates ORM capacity and hippocampal dynamic functional connectivity in PD. Thirty-one PD participants and 31 healthy controls (HC) underwent functional MRI during an ORM task. Co-activation pattern analysis identified active hippocampal networks. The PD group showed impaired ORM and a sequence of four activated hippocampal networks. The fourth network, involving the dorsal Attention Network (dAN), had fewer and shorter expressions during correct ORM responses in PD compared with HC. Hippocampal functional asymmetry was observed in HC but not in PD. These findings suggest that impaired ORM in PD is linked to reduced hippocampal functional asymmetry. Future research should explore differences in functional dynamics of odor memory-related brain regions in PD patients with and without cognitive decline.

National Category
Neurosciences
Identifiers
urn:nbn:se:su:diva-241824 (URN)10.1038/s41531-025-00906-3 (DOI)001449991400002 ()2-s2.0-105000866934 (Scopus ID)
Available from: 2025-04-10 Created: 2025-04-10 Last updated: 2025-04-10Bibliographically approved
Ruane, R., Lampert, O., Larsson, M., Vetrano, D. L., Laukka, E. J. & Ekström, I. (2025). Olfactory Deficits and Mortality in Older Adults. JAMA Otolaryngology - Head and Neck Surgery
Open this publication in new window or tab >>Olfactory Deficits and Mortality in Older Adults
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2025 (English)In: JAMA Otolaryngology - Head and Neck Surgery, ISSN 2168-6181, E-ISSN 2168-619XArticle in journal (Refereed) Epub ahead of print
Abstract [en]

Importance  Olfactory deficits are associated with higher mortality in older adults, but the mechanisms remain unclear. Further understanding this relationship could inform interventions to improve survival and quality of life for those with olfactory deficits.

Objective  To investigate the association of olfactory deficits with all-cause and cause-specific mortality and to explore potential mediating factors.

Design, Setting, and Participants  The Swedish National Study on Aging and Care in Kungsholmen (SNAC-K), is an ongoing population-based, longitudinal cohort study with baseline between 2001 and 2004. Eligible participants were residents of Kungsholmen, Stockholm, Sweden, and aged between 60 and 99 years from March 21, 2001, to August 30, 2004. Twelve-year follow-up was completed in February 2013. Data analysis took place between February 2024 and July 2024.

Main Outcomes and Measures  Olfactory ability was tested with the 16-item Sniffin’ Sticks Odor Identification task. Mortality was determined through the Swedish National Cause of Death Register. Cox proportional hazards models examined the associations between olfaction and mortality over 6 years and 12 years. Competing hazard risks regression analyses assessed the olfactory-mortality association for specific death causes. Generalized structural equation models investigated mediators, including incident dementia, baseline chronic diseases, frailty, and malnutrition. The tested hypotheses were formulated after data collection.

Results  Among 2524 participants (baseline mean [SD] age, 71.9 [10.0] years; 1545 [61.2%] female), 445 (17.6%) had died at 6 and 969 (38.4%) at 12 years of follow-up. Each additional incorrect answer on the odor identification test was associated with a 6% increased all-cause mortality risk at 6 years (hazard ratio [HR], 1.06 [95% CI, 1.03-1.08]) and 5% increased risk at 12 years (HR, 1.05 [95% CI, 1.03-1.08]) in multiadjusted models. In cause-specific models, the olfaction-mortality association had the greatest risk in relation to neurodegenerative death causes. Meaningful mediators for death at 6 years included dementia (23% of total association), frailty (11% of total association), and malnutrition (5% of total association). At 12 years, frailty remained a mediator (9% of total association).

Conclusions and Relevance  The results of this cohort study underscore the importance of olfactory function as a mortality risk marker in older adults and highlight the evolving influence of neurodegeneration and frailty on this relationship. Further research is needed to assess the clinical utility of olfactory assessments in identifying individuals at risk of adverse health outcomes.

National Category
Gerontology, specialising in Medical and Health Sciences
Identifiers
urn:nbn:se:su:diva-243072 (URN)10.1001/jamaoto.2025.0174 (DOI)001464852200001 ()2-s2.0-105002747994 (Scopus ID)
Available from: 2025-05-09 Created: 2025-05-09 Last updated: 2025-05-09
Almkvist, O., Larsson, M. & Graff, C. (2024). Odor Identification Across Time in Mutation Carriers and Non-Carriers in Autosomal-Dominant Alzheimer’s Disease. Journal of Alzheimer's Disease, 97(2), 587-598
Open this publication in new window or tab >>Odor Identification Across Time in Mutation Carriers and Non-Carriers in Autosomal-Dominant Alzheimer’s Disease
2024 (English)In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 97, no 2, p. 587-598Article in journal (Refereed) Published
Abstract [en]

Background: Impaired odor identification is a characteristic of sporadic Alzheimer’sdisease(AD), but its presence in autosomal-dominantAD (adAD) remains uncertain. Objective: To investigate odor identification ability in mutation carriers (MC) and non-carriers (NC) of adAD in relation to years to estimated clinical onset clinical onset (YECO) of disease. Methods: Participants from six families with autosomal-dominant mutations (APP Swedish, APPArctic, and PSEN1 mutations) included 20 MC and 20 NC. The groups were comparable in age, gender, education, number of APOE ɛ4 alleles, and YECO, but differed in global cognition (Mini-Mental State Examination). The MC group included individuals in asymptomatic, symptomatic cognitively unimpaired, mild cognitive impairment, and dementia stages of disease, spanning approximately 40 years of the AD continuum. All NC were asymptomatic. Olfactory function was assessed by means of free and cued identification of common odors summarized as total identification. Results: MC performed poorer than NC in free and total identification. Four MC and none of the NC were anosmic. Olfactory functions in MC and NC were significantly and inversely related to time course (YECO) for both free and total identification. The decline in free identification began approximately 10 years prior to the estimated clinical onset of AD in MC. Odor identification proficiency was associated with episodic memory and executive function in MC and NC. Conclusions: Impaired odor identification is present well before the clinical diagnosis of AD in MC and is associated with disease progression. Odor identification ability may be a useful early biomarker for adAD.

Keywords
Alzheimer’s disease, autosomal-dominant Alzheimer’s disease, cognition, mutation carriers, non-carriers, odor identification
National Category
Psychology
Research subject
Psychology
Identifiers
urn:nbn:se:su:diva-225114 (URN)10.3233/jad-230618 (DOI)001168502800007 ()38160354 (PubMedID)2-s2.0-85183204076 (Scopus ID)
Available from: 2024-01-08 Created: 2024-01-08 Last updated: 2025-01-08Bibliographically approved
Laukka, E. J., Ekström, I., Larsson, M., Grande, G., Fratiglioni, L. & Rizzuto, D. (2023). Markers of olfactory dysfunction and progression to dementia: A 12-year population-based study. Alzheimer's & Dementia: Journal of the Alzheimer's Association, 19(7), 3019-3027
Open this publication in new window or tab >>Markers of olfactory dysfunction and progression to dementia: A 12-year population-based study
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2023 (English)In: Alzheimer's & Dementia: Journal of the Alzheimer's Association, ISSN 1552-5260, E-ISSN 1552-5279, Vol. 19, no 7, p. 3019-3027Article in journal (Refereed) Published
Abstract [en]

Introduction: We evaluated markers of olfactory dysfunction (OD) for estimating hazard of dementia in older adults.

Methods: Mild (hyposmia) and severe (anosmia) OD was classified in a population-based study of dementia-free persons (SNAC-K; n = 2473; mean age = 70 years) using the Sniffin sticks odor identification task. Combined variables were created for objective and subjective OD and for OD and APOE status. Hazard of dementia across 12 years was estimated with Cox regression.

Results: OD was associated with increased hazard of dementia (2.01; 95% confidence interval [CI] 1.60-2.52), with the strongest association for anosmia (2.92; 95% CI 2.14-3.98). Results remained consistent after adjusting for potential confounders and across age and sex subgroups. APOE ε4 carriers with anosmia had the highest hazard of dementia (ε4: 6.95; 95% CI 4.16-11.62; ε4/ε4: 19.84; 95% CI 6.17-63.78).

Discussion: OD is associated with increased risk of dementia, especially severe impairment in combination with genetic risk of Alzheimer's disease.

Keywords
APOE, dementia, olfaction, population-based study, preclinical marker
National Category
Gerontology, specialising in Medical and Health Sciences Neurology
Identifiers
urn:nbn:se:su:diva-238913 (URN)10.1002/alz.12932 (DOI)000919500800001 ()36689643 (PubMedID)2-s2.0-85147026888 (Scopus ID)
Available from: 2025-02-03 Created: 2025-02-03 Last updated: 2025-02-03Bibliographically approved
Eek, T., Lundin, F., Larsson, M., Hamilton, P. & Georgiopoulos, C. (2023). Neural suppression in odor recognition memory. Chemical Senses, 48, Article ID bjad001.
Open this publication in new window or tab >>Neural suppression in odor recognition memory
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2023 (English)In: Chemical Senses, ISSN 0379-864X, E-ISSN 1464-3553, Vol. 48, article id bjad001Article in journal (Refereed) Published
Abstract [en]

Little is known about the neural basis of lower- and higher-order olfactory functions such as odor memory, compared with other sensory systems. The aim of this study was to explore neural networks and correlates associated with 3 functions: passive smelling (PS), odor encoding (OE), and in particular odor recognition memory (ORM). Twenty-six healthy participants were examined using functional magnetic resonance imaging conducted across 3 sessions, one for each function. Independent component analysis revealed a difference between sessions where a distinct ORM component incorporating hippocampus and posterior cingulate showed delayed triggering dissociated from odor stimulation and recognition. By contrasting Hit for ORM (target odors correctly recognized as old) and a combination of PS and detected odors from OE, we found significantly lower activations in amygdala, piriform cortex, insula, thalamus, and the inferior parietal lobule. Region of interest analysis including anterior insula, posterior cingulate gyrus, dentate gyrus, left middle frontal gyrus, amygdala, and piriform cortex demonstrated that Hit were associated with lower activations compared with other memory responses. In summary, our findings suggest that successful recognition of familiar odors (odor familiarity) is associated with neural suppression in the abovementioned regions of interest. Additionally, network including the hippocampus and posterior cingulate is engaged in a postrecognition process. This process may be related to incidental encoding of less familiar and more novel odors (odor novelty) and should be subject for future research.

Place, publisher, year, edition, pages
Oxford University Press, 2023
Keywords
episodic memory, olfaction, functional magnetic resonance imaging (fMRI), independent component analysis (ICA), region of interest analysis (ROI), familiarity
National Category
Neurosciences Psychology
Research subject
Psychology
Identifiers
urn:nbn:se:su:diva-216003 (URN)10.1093/chemse/bjad001 (DOI)000935468800001 ()36715106 (PubMedID)2-s2.0-85148678888 (Scopus ID)
Note

The study was supported by Linköping University Hospital Research Fund grant number RÖ-938229, Forskningsrådet i Sydöstra Sverige grant number FORSS-931891.

Available from: 2023-03-31 Created: 2023-03-31 Last updated: 2024-01-11Bibliographically approved
Raj, R., Hörberg, T., Lindroos, R., Larsson, M., Herman, P., Laukka, E. J. & Olofsson, J. K. (2023). Odor identification errors reveal cognitive aspects of age-associated smell loss. Cognition, 236, Article ID 105445.
Open this publication in new window or tab >>Odor identification errors reveal cognitive aspects of age-associated smell loss
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2023 (English)In: Cognition, ISSN 0010-0277, E-ISSN 1873-7838, Vol. 236, article id 105445Article in journal (Refereed) Published
Abstract [en]

Human olfaction can be extraordinarily sensitive, and its most common assessment method is odor identification (OID), where everyday odors are matched to word labels in a multiple-choice format. However, many older persons are unable to identify familiar odors, a deficit that is associated with the risk of future dementia and mortality. The underlying processes subserving OID in older adults are poorly understood. Here, we analyzed error patterns in OID to test whether errors could be explained by perceptual and/or semantic similarities among the response alternatives. We investigated the OID response patterns in a large, population-based sample of older adults in Sweden (n = 2479; age 60–100 years). Olfaction was assessed by a ‘Sniffin ́ TOM OID test with 16 odors; each trial involved matching a target odor to a correct label among three distractors. We analyzed the pattern of misidentifications, and the results showed that some distractors were more frequently selected than others, suggesting cognitive or perceptual factors may be present. Relatedly, we conducted a large online survey of older adults (n = 959, age 60–90 years) who were asked to imagine and rate the perceptual similarity of the target odors and the three corresponding distractors (e.g. “How similar are these smells: apple and mint?”). We then used data from the Swedish web corpus and the Word2Vec neural network algorithm to quantify the semantic association strength between the labels of each target odor and its three distractors. These data sources were used to predict odor identification errors. We found that the error patterns were partly explained by both the semantic similarity between target-distractor pairs, and the imagined perceptual similarity of the target-distractor pair. Both factors had, however, a diminished prediction in older ages, as responses became gradually less systematic. In sum, our results suggest that OID tests not only reflect olfactory perception, but also likely involve the mental processing of odor-semantic associations. This may be the reason why these tests are useful in predicting dementia onset. Our insights into olfactory-language interactions could be harnessed to develop new olfactory tests that are tailored for specific clinical purposes.

Place, publisher, year, edition, pages
Elsevier, 2023
Keywords
smell, odor identification, olfactory perception, semantics, aging, memory
National Category
Psychology
Research subject
Psychology
Identifiers
urn:nbn:se:su:diva-218893 (URN)10.1016/j.cognition.2023.105445 (DOI)37027897 (PubMedID)2-s2.0-85151520491 (Scopus ID)
Funder
Knut and Alice Wallenberg FoundationSwedish Research Council, 2020-00266Swedish Research Council, 2021-03440
Available from: 2023-06-26 Created: 2023-06-26 Last updated: 2024-01-13Bibliographically approved
Laukka, E. J., Palmquist, E., Ekström, I., Olofsson, J. K., Dintica, C. S., Bäckman, L. & Larsson, M. (2023). Olfactory impairment and domain‐specific cognitive decline: A 12‐year population‐based study. Alzheimer's & Dementia: Journal of the Alzheimer's Association, 19(S18), Article ID e074572.
Open this publication in new window or tab >>Olfactory impairment and domain‐specific cognitive decline: A 12‐year population‐based study
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2023 (English)In: Alzheimer's & Dementia: Journal of the Alzheimer's Association, ISSN 1552-5260, E-ISSN 1552-5279, Vol. 19, no S18, article id e074572Article in journal (Refereed) Published
Abstract [en]

Background: Olfactory impairment has been associated with both cognitive impairment and dementia and Alzheimer’s disease (AD). This study aimed to investigate the association between olfactory dysfunction (OD) and change trajectories in different cognitive domains in aging. Method: Participants (n = 2473, mean age = 72 years, 61% female) from the population-based Swedish National study on Aging and Care-Kungsholmen (SNAC-K) were repeatedly assessed with tasks measuring episodic memory, semantic memory, verbal fluency, and perceptual speed across 12 years. OD was measured at baseline and participants were categorized as normosmic, hyposmic, or anosmic based on the Sniffin’ Sticks odor identification task. Linear mixed-effects models were used to assess the associations between baseline OD and rates of cognitive decline. Result: OD was related to poorer baseline performance and faster rates of decline during follow-up in all examined domains, as well as in global cognition. Associations were generally more pronounced for anosmia compared to hyposmia. Conclusion: Olfactory impairment is associated with accelerated decline in aging across a wide range of cognitive domains.

Place, publisher, year, edition, pages
John Wiley & Sons, 2023
Keywords
olfactory impairment, cognitive impairment, dementia, Alzheimer’s disease, aging
National Category
Psychology
Research subject
Psychology
Identifiers
urn:nbn:se:su:diva-225120 (URN)10.1002/alz.074572 (DOI)
Available from: 2024-01-08 Created: 2024-01-08 Last updated: 2024-01-12Bibliographically approved
Herz, R. S., Larsson, M., Trujillo, R., Casola, M. C., Ahmed, F. K., Lipe, S. & Brashear, M. E. (2022). A three-factor benefits framework for understanding consumer preference for scented household products: psychological interactions and implications for future development. Cognitive Research Principles and Implications, 7(1), Article ID 28.
Open this publication in new window or tab >>A three-factor benefits framework for understanding consumer preference for scented household products: psychological interactions and implications for future development
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2022 (English)In: Cognitive Research Principles and Implications, ISSN 2365-7464, Vol. 7, no 1, article id 28Article in journal (Refereed) Published
Abstract [en]

Humans have deliberately scented their environment for purpose or pleasure for millennia. In the contemporary marketplace most consumers prefer and purchase scented versions of common household products. However, the drivers of this consumer preference have not been elucidated. To explain the attraction to scent in household products we propose a novel three-factor framework, comprising functional benefits (malodor mitigation, base odor coverage, freshening), in-use experience benefits (cleanliness, efficacy, pleasure), and emotional benefits (increasing in confidence, mood and nostalgia). To support this framework, we present new data from a market research survey on US consumer purchasing habits and attitudes towards home cleaning, laundry, and air freshening products. Further substantiating our framework, a focused review of olfactory psychological science illustrating the central role of scent in cognition, wellbeing, motivated behavior, and social behavior, as well as sensory marketing research highlights the benefits and implications of scent in consumer household products. Based on our three-factor framework we go on to discuss the potential for scent to influence health and raise issues to consider (such as potential negative responding to fragranced products). We conclude by showcasing new opportunities for future research in olfactory science and on scented household products that can advance the positive impacts of scent.

Keywords
scent, olfaction, emotion, memory, perception, cognition, motivated behaviour, social behaviour, confidence, health, quality of life, scent marketing, sensory marketing, cross-modal interactions, household consumer products, consumer behaviour, three-factor framework
National Category
Psychology
Research subject
Psychology
Identifiers
urn:nbn:se:su:diva-204035 (URN)10.1186/s41235-022-00378-6 (DOI)000777172600002 ()35362845 (PubMedID)
Available from: 2022-04-21 Created: 2022-04-21 Last updated: 2023-01-03Bibliographically approved
Oleszkiewicz, A., Schriever, V. A., Valder, C., Agosin, E., Altundag, A., Avni, H., . . . Gellrich, J. (2022). Hedonic perception of odors in children aged 5–8 years is similar across 18 countries: Preliminary data. International Journal of Pediatric Otorhinolaryngology, 157, Article ID 111129.
Open this publication in new window or tab >>Hedonic perception of odors in children aged 5–8 years is similar across 18 countries: Preliminary data
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2022 (English)In: International Journal of Pediatric Otorhinolaryngology, ISSN 0165-5876, E-ISSN 1872-8464, Vol. 157, article id 111129Article in journal (Refereed) Published
Abstract [en]

Objective: Olfactory preference emerges very early in life, and the sense of smell in children rapidly develops until the second decade of life. It is still unclear whether hedonic perception of odors is shared in children inhabiting different regions of the globe.

Methods: Five-hundred ten healthy children (N = 510; ngirls = 256; nboys = 254) aged from 5 to 8 years from 18 countries rated the pleasantness of 17 odors.

Results: The hedonic perception of odors in children aged between 5 and 8 years was rather consistent across 18 countries and mainly driven by the qualities of an odor and the overall ability of children to label odorants.

Conclusion: Conclusions from this study, being a secondary analysis, are limited to the presented set of odors that were initially selected for the development of U-Sniff test and present null findings for the cross-cultural variability in hedonic perception of odors across 18 countries. These two major issues should be addressed in the future to either contradict or replicate the results presented herewith. This research lays fundament for posing further research questions about the developmental aspects of hedonic perception of odors and opens a new door for investigating cross-cultural differences in chemosensory perception of children.

Keywords
hedonic perception, olfaction, children, psychophysiology, odor identification
National Category
Psychology Otorhinolaryngology
Research subject
Psychology
Identifiers
urn:nbn:se:su:diva-206219 (URN)10.1016/j.ijporl.2022.111129 (DOI)000849774200009 ()35443229 (PubMedID)2-s2.0-85128360476 (Scopus ID)
Available from: 2022-06-17 Created: 2022-06-17 Last updated: 2023-01-03Bibliographically approved
Sorokowska, A., Nord, M., Stefańczyk, M. M. & Larsson, M. (2022). Odor-based context-dependent memory: influence of olfactory cues on declarative and nondeclarative memory indices. Learning & memory (Cold Spring Harbor, N.Y.), 29(5), 136-141
Open this publication in new window or tab >>Odor-based context-dependent memory: influence of olfactory cues on declarative and nondeclarative memory indices
2022 (English)In: Learning & memory (Cold Spring Harbor, N.Y.), ISSN 1072-0502, E-ISSN 1549-5485, Vol. 29, no 5, p. 136-141Article in journal (Refereed) Published
Abstract [en]

Reinstating the olfactory learning context can increase access to memory information, but it is not fully clear which memory functions are subject to an enhancing odor context reinstatement effect. Here, we tested whether congruent odor context during encoding and recall positively affected declarative and nondeclarative memory scores using a novel method for manipulation of an odorous environment; namely, intranasal Nosa plugs. Recall of a text and a complex figure as well as performance in a priming task were assessed immediately and 1 wk after encoding. We found that congruent odor exposure at encoding and recall aided free retrieval of a story at delayed testing but had no significant effect on a complex figure recall or a word completion task. Differences between the assessed memory indices suggest that olfactory environmental cues may be primarily efficient in free verbal recall tasks. 

Keywords
fragrance, association, odor, recall, cues, mental recall, odorants, smell
National Category
Psychology
Research subject
Psychology
Identifiers
urn:nbn:se:su:diva-208699 (URN)10.1101/lm.053562.121 (DOI)000810242500003 ()35483742 (PubMedID)2-s2.0-85129779407 (Scopus ID)
Available from: 2022-09-08 Created: 2022-09-08 Last updated: 2023-01-04Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0003-3418-0700

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