Olfactory deficits are hypothesized to precede cognitive decline and be independently associated with future dementia. Conversely, the concurrency of cognitive and olfactory impairments is expected to represent an advanced stage, associated with shorter time to diagnosis. Limited research has examined the association of isolated and concurrent cognitive and olfactory impairments with incident dementia. We aimed to estimate the 12-year dementia hazard for cognitive impairment no dementia (CIND), olfactory dysfunction (OD), and their combination in a population-based cohort of older adults. We classified 2406 participants from the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K) based on baseline CIND and OD. Dementia hazard was estimated with Cox regressions for the whole period and two timeframes (baseline to 6-year follow-up and 6- to 12-year follow-up), and time until receiving a diagnosis via Laplace regressions. CIND+OD was associated with increased hazard ratio (HR) of dementia over 6 years (HR 11.38; 95% CI 6.70, 19.32; p < 0.001), higher for amnestic CIND+OD (HR 22.23; 95% CI 11.79, 41.90; p < 0.001). Isolated CIND was associated with dementia closest to baseline (HR 3.38; 95% CI 1.75, 6.49; p < 0.001), while isolated OD was associated with dementia closest (HR 2.56; 95% CI 1.48, 4.43; p < 0.001) and furthest (HR 2.12; 95% CI 1.41, 3.19; p < 0.001) to baseline. CIND+OD received their dementia diagnosis 3 years earlier. This study demonstrated that individuals with both cognitive and olfactory impairments have a higher short-term risk of progression to dementia and that OD may be a valuable early marker of dementia on its own.

Background: The combination of olfactory and cognitive markers has shown promising results in classifying individuals at different risk levels of dementia. We aimed to examine the association of isolated and combined olfactory dysfunction (OD) and cognitive impairment (CI) with incident dementia across 12 years and across two timeframes (0-6 years and 6-12 years) to evaluate whether the association varies over time.

Method: The sample was comprised of 2406 older adults (M_age=71.5 years, %_females=60.8%) from the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K), free of dementia at baseline with available baseline odor identification (Sniffin’ Sticks test, range 0–16) and cognition (five cognitive domains) data. Participants were classified as having OD (performance <11) and as CI no dementia (CIND, ≥1.5 SD below the age-specific mean in at least one domain). CIND was further classified based on memory impairment (amnestic vs. non-amnestic). Dementia hazard was estimated with Cox regression analyses for the whole study period (baseline to 12-year follow-up) and two timeframes (baseline to 6-year follow-up and 6- to 12-year follow-up) for isolated OD, isolated CIND, and their combination. Laplace regression was applied to assess the time until 5% of participants in each group received a dementia diagnosis, based on the 5% of incident dementia in the unimpaired participants (reference) over the whole period.

Result: There were 1403 unimpaired, 326 isolated CIND, 476 isolated OD, and 203 CIND+OD individuals. CIND+OD was associated with increased dementia risk over the first 6-year follow-up (HR, 95% CI: 11.38, 6.70–19.32), more pronounced for amnestic CIND (22.23, 11.79–41.90). Isolated OD was associated with increased dementia risk over both periods (baseline to 6-year follow-up: 2.56, 1.48–4.43, baseline to 12-year follow-up: 2.12, 1.41–3.19), while isolated CIND was associated with dementia only over the first period (3.38, 1.75–6.49). 5% of CIND+OD individuals progressed to dementia 5 years after baseline, while isolated CIND and isolated OD reached the same proportion after 8 years.

Conclusion: Concurrent CI and OD may signal incipient dementia in the coming years, especially for amnestic individuals. OD is a potential early marker of dementia on its own.

Olfactory impairment is common in older age and is a known early feature of several dementia diseases. Blood-based biomarkers of Alzheimer’s disease (AD) now offer a scalable method for detecting pathophysiological mechanisms related to olfactory decline in the general population. However, few studies have examined how these biomarkers relate to long-term olfactory trajectories. Most existing work has been limited to cross-sectional settings. In this population-based study, we used biomarker data collected at baseline and followed participants for up to 15 years, enabling us to test whether early biological changes are temporally linked to subsequent olfactory decline. Data came from the ongoing Swedish National Study on Aging and Care in Kungsholmen (SNAC-K), a longitudinal population-based study with baseline assessments from March 21, 2001, through August 30, 2004. We included participants without prevalent neurodegenerative diseases who completed olfactory assessment at baseline. The 15-year follow-up was finished in December 2019. Data were analysed from December 2023 to April 2024. Serum-derived biomarkers of tau phosphorylated at threonine 217 (p-tau217) and at theorine181 (p-tau181), total tau (t-tau), amyloid-β ratio (Aβ42/Aβ40), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) were obtained at baseline. Linear mixed models examined associations between biomarker quartiles and Sniffin’ Sticks odor identification performance over 15 years, adjusting for demographics, health conditions, and semantic knowledge. We included 1868 participants (mean [SD] age 71.3 [9.9] years; 1122 females [60.1%]). In fully adjusted models, higher quartiles of p-tau217, p-tau181, NfL, and GFAP, and lower quartiles of Aβ42/Aβ40, were associated with steeper olfactory decline, with the steepest decline among participants in the highest quartiles (β for Q4 vs Q1: -0.20 [95% CI: -0.26 to -0.15] for p-tau217; -0.19 [95% CI: -0.25 to -0.13] for p-tau181; -0.23 [95% CI: -0.29 to -0.17] for NfL; β = -0.17 [95% CI: -0.23 to -0.11] for GFAP. Participants in the lowest Aβ42/Aβ40 quartile declined more steeply than those in the highest (β = -0.09 [95% CI: -0.14 to -0.04]). Associations appeared stronger in the oldest participants, in APOE ε4 carriers for p-tau181, in non-carriers for NfL and GFAP, and among former smokers for NfL. Blood-based biomarkers of AD were consistently associated with faster olfactory decline in older adults, particularly in the highest biomarker quartiles. These results provide large-scale longitudinal evidence, across up to 15 years of follow-up, that olfactory decline in the general population is linked to AD-related blood biomarkers, supporting the hypothesis that common olfactory losses in ageing partly reflect dementia-related processes.

Background: The mechanisms underlying olfactory decline in aging need further investigation. Noticeably, the longitudinal relationship of biological markers with olfaction remains underexplored. We investigated whether baseline levels and progression of microvascular lesions and brain atrophy are associated with odor identification (OID) decline.

Methods: The association between structural MRI markers and OID decline was examined in participants from the SNAC-K MRI study who were free from dementia at baseline (n = 401, mean age = 70.2 years, 60% females). OID was repeatedly assessed over 15 years. Presence of lacunes, white matter hyperintensities (WMH), perivascular spaces (PVS), and lateral ventricular, hippocampal, amygdalar, and total gray matter (GM) volumes were assessed up to 6 years, concurrent with the first 6 years of olfactory assessments.

Results: Higher PVS count and lower hippocampal and GM volumes at baseline were associated with accelerated OID decline (p_FWE < 0.05). Longitudinally (n = 225), presence of lacunes at follow-up, faster WMH volume and PVS count increases, faster lateral ventricular enlargement, and faster hippocampal, amygdalar, and GM atrophy were associated with accelerated OID decline (p_FWE < 0.05).

Conclusion: Olfactory decline is related to both increased cerebrovascular burden and accelerated brain atrophy over time.

Naming common odors can be an exceptionally challenging task even for young and healthy individuals. Due to this difficulty, tests of cued odor identification (OID) are used instead of free odor identification in cognitive, neuropsychological, or aging research. Consequently, our understanding of the cognitive demands of free OID is limited. In this study, we analyze the demographic and cognitive factors that influence OID responses of old adults. We utilize a uniquely large dataset (n = 2,479) from a population-based sample of healthy, older Swedish adults (ages 58–102) who participated in free and cued OID using the 16-item Sniffin’ TOM test. The free OID naming responses were categorized as correct, misnamings, or omissions. The results revealed that omissions are surprisingly prevalent, constituting 66.4% of errors and accounting for 87.7% of the age-related differences in task performance. Additionally, we hypothesized that successful free OID would be more closely linked to nonolfactory cognitive abilities, such as verbal fluency, vocabulary, and episodic memory proficiency. This hypothesis was supported, as we found significant associations between free OID and these cognitive abilities, while cued OID identification only was associated with perceptual speed. Our findings suggest that the assessment of free OID may provide valuable insights into odor-based cognition, indicating a need for further research in this area.

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.

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.

Memory decline is a central cognitive symptom in Parkinson’s Disease (PD). While task-fMRI studies link hippocampal activity (AHA) to poorer memory and olfactory performance, this relationship during rest remains understudied. The objectives of this study are to examine differences in resting-state hippocampal networks, explore the occurrence of reduced AHA within these networks, and investigate its impact on memory and olfaction in PD. Thirty-nine PD patients awaiting evaluation for device-aided Parkinson therapy and 46 healthy controls (HC) underwent resting-state fMRI (rs-fMRI). PD patients also completed a memory and olfactory assessment. Co-activation pattern (CAP) analysis was performed on the rs-fMRI data. Our results demonstrated reduced activity in two hippocampal networks in PD: Network 1, incorporating the visual cortex, cerebellum, superior parietal lobule, and precuneus, and Network 5, incorporating parts of the central executive network. PD subgroups with reduced AHA in Network 1 and 5 performed significantly worse on tests of auditory-verbal short-term, long-term and recognition memory, as well as odor identification. In conclusion, within specific resting-state hippocampal networks, reduced AHA in PD is linked to poorer auditory-verbal memory and odor identification.

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.

INTRODUCTION: We evaluated short versions of a 16-item odor identification (OID) test, with regard to their ability to identify individuals at high dementia risk.

METHODS: Participants from the population-based SNAC-K study (n = 2418) were followed across 12 years. We formed 13 abbreviated clusters based on the identifiability and perceptual characteristics of the Sniffin’ Sticks Test (SST) items, and pre-existing test versions. Dementia hazard was estimated with Cox regressions.

RESULTS: Lower OID scores were associated with an increased dementia hazard across all odor clusters. Lower performance in the high identifiability cluster showed the strongest association with dementia (hazard ratio = 1.39, 95% confidence interval [1.28–1.51]). Moreover, the high-intensity odor cluster showed a stronger association with dementia than the low-intensity cluster (P = 0.02).

DISCUSSION: The findings suggest that the SST items differ with regard to their association with dementia and support using a reduced set size for clinical practice.