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.

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.

Introduction: Cognitive reserve (CR) describes individual differences in susceptibility to brain damage that translates into varying dementia onsets and may also influence the occurrence of depressive symptoms. Within a population-based cohort of older people, we investigated two operationalizations of CR, residual- and activity-based approaches, in their association with the development of depressive symptoms.

Methods: We analyzed longitudinal data on 402 dementia- and depression-free adults aged 60+ from the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K) who underwent brain MRI at baseline. Residual-based reserve was derived by regressing episodic memory on a brain-integrity index incorporating six structural MRI markers. Activity-based reserve factored lifelong CR-enhancing experiences, including education, work complexity, social network, and leisure activities. Clinically relevant depressive symptoms were defined as a Montgomery–Åsberg Depression Rating Scale score >6. Cox hazard models were used to explore the association between both residual- and activity-based CR measures (categorized in tertiles) and incidence of depressive symptoms over a 15-year follow-up, while accounting for sociodemographic, clinical, behavioral factors, and brain integrity. Analyses for the activity-based measure were replicated in the full SNAC-K sample (N = 2709), further exploring depression diagnosis as additional outcome.

Results: Compared to low levels, higher levels of residual-based CR were associated with a lower hazard of depressive symptom onset in fully adjusted models (HR: .43, 95%CI .22, .84). While activity-based CR was not significantly associated with developing depressive symptoms in the MRI subsample (HRhigh .47, 95%CI .21, 1.04), it was in the full sample (HRhigh .52, 95%CI .39, .71). Activity-based CR was further associated with depression diagnoses in the full sample (HRhigh: .45, 95%CI .31, .65).

Discussion: Largely independent of its measurement, CR appears to influence depressive symptomatology in late life. Reserve-enhancing initiatives may be beneficial not only for cognitive but also for mental health in older people.

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.

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.

Background: Olfactory impairment is associated with dementia in clinical settings. We examined the relationship of olfactory identification function with all-cause dementia, Alzheimer's disease (AD), and vascular dementia (VaD) and assessed the discriminative ability of the Sniffin' Sticks Identification Test (SSIT), the self-rated Ascertain Dementia 8-item Questionnaire (AD8), and their combination for dementia detection among rural-dwelling older adults in China.

Methods: This population-based cross-sectional study included 4481 participants (age ≥ 65 years; 56.8% women; 38.1% illiteracy) living in rural communities. The 16-item SSIT was performed to assess olfactory identification function. The self-rated AD8 was administered to participants for cognitive status. We diagnosed dementia, AD, and VaD following the international criteria. Data were analyzed with logistic regression models and receiver operating characteristic curve.

Results: Of the 4481 participants, dementia was diagnosed in 139 persons (3.1%), including 92 with AD and 42 with VaD. The SSIT score (range, 0–16) was associated with multiadjusted odds ratios of 0.83 (95% CI: 0.79–0.88) for dementia, 0.84 (0.79–0.90) for AD, and 0.79 (0.71–0.87) for VaD. The area under the curve for the discrimination between participants with and without dementia was 0.73 (95% CI: 0.69–0.77) for SSIT score ≤ 8 alone, 0.86 (0.82–0.89) for self-rated AD8 score ≥ 3 alone, and 0.89 (0.86–0.92) for their combination using a logistic model.

Conclusions: Olfactory impairment is a clinical marker for all-cause dementia, AD, and VaD. The smell identification test, in combination with the brief self-rated cognitive screening tool, is accurate for screening dementia among rural-dwelling Chinese older adults with no or limited education.

BACKGROUND: Olfactory impairment is increasingly common with older age, which may be in part explained by cumulative effects of exposure to inhaled toxins. However, population-based studies investigating the relationship between air pollution and olfactory ability are scarce.

OBJECTIVES: We aimed to investigate associations between exposure to common air pollutants and longitudinal change in odor identification.

METHODS: Our study of 2,468 participants (mean age = 72.3 y; 61.1% female), of which 1,774 participants (mean age = 70.5 y; 61.9% female) had at least two olfactory assessments over 12 y of follow-up from the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K), Stockholm, Sweden. Participants were free from cognitive impairment and neurodegenerative disease at baseline. Odor identification ability was assessed with Sniffin' Sticks. Change in olfactory performance was estimated with linear mixed models. Exposure to two major airborne pollutants [particulate matter with aerodynamic diameter <= 2.5 mu m (PM2.5) and nitrogen oxides (NOx)] for the 5 y preceding baseline was assessed using spatiotemporal dispersion models for outdoor levels at residential addresses.

RESULTS: Participants showed significant decline in odor identification ability for each year in the study {f3 = - 0.20 [95% confidence interval (CI): -0.22, 0.18; p < 0.001]}. After adjustment for all covariates, residents of third [f3= - 0.09 (95% CI: -0.14, -0.04; p < 0.001)] and fourth [f3 = - 0.07 (95% CI: -0.12, -0.02; p = 0.005)] exposure quartiles of PM2.5 had faster rates of olfactory decline than residents from the first quartile. Similar results were observed for the third [f3= - 0.05 (95% CI: -0.10, -0.01; p = 0.029)] and fourth [f3= - 0.07 (95% CI: -0.11, -0.02; p = 0.006) quartiles of NOx].

DISCUSSION: Our results suggest an association between air pollution exposure and subsequent olfactory decline. We speculate that cumulative effects of airborne pollutants on the olfactory system may be one underlying cause of olfactory impairment in aging. 

Background: Self-rated subjective cognitive decline (SCD) and subjective olfactory impairment (SOI) are associated with objective cognitive decline and dementia. However, their relationship and co-occurrence is unknown. We aimed to (a) describe the occurrence of SOI, SCD and their overlap in the general population; (b) compare SOI and SCD in terms of longitudinal associations with corresponding objective olfactory and cognitive measures; and (c) describe how SOI and SCD may lead to distinct sensory and cognitive outcomes.

Methods: Cognitively unimpaired individuals from the third wave of the Swedish population-based Betula study (n = 784, aged 35–90 years; 51% females) were split into self-rated SOI, SCD, overlapping SCD + SOI, and controls. Between-subject and within-subject repeated-measures MANCOVA were used to compare the groups regarding odor identification, cognition, age, sex, and education. Spearman correlation was used to assess the different patterns of association between olfaction and cognition across groups.

Results: SOI was present in 21.1%, whereas SCD was present in 9.9% of participants. According to a chi-square analysis, the SCD + SOI overlap (2.7%) is on a level that could be expected if the phenomena were independent. Odor identification in SOI showed decline at the 10-year follow-up (n = 284) and was positively associated with cognition. The SOI and SCD groups showed distinct cognitive-olfactory profiles at follow-up.

Conclusions: SOI occur independently of SCD in the population, and these risk factors are associated with different cognitive and olfactory outcomes. The biological causes underlying SOI and SCD, as well as the risk for future cognitive impairment, need further investigation.

Importance Olfactory deficits are common in aging and associated with several conditions linked to inflammation. A few studies suggest that increased concentration of pro-inflammatory biomarkers may be related to olfactory deficits, but these associations are understudied in population-based samples. Objective To investigate the association between serum concentrations of C-reactive protein (CRP) and olfactory identification level as well as rate of change in aging. Methods We included 1,721 participants (mean age 70.5 years; 61.9% female) with at least two olfactory assessments across the 12-year follow-up. Baseline level and change in odor identification were estimated with linear mixed models as a function of CRP levels, derived from blood plasma at baseline. Results Results indicated a negative dose-response association between CRP level and odor identification scores at baseline, after adjustment for demographic, cognitive, health, and lifestyle factors. CRP levels ranging between 11 and 20 mg/L were significantly related to lower olfactory ability (beta = -0.811, 95% confidence interval [CI] [-1.503 to -0.118]; p = .022). Likewise, CRP values above 20 mg/L were related to lower olfactory scores, an association that approached statistical significance (beta = -0.996, 95% CI [-2.045 to 0.054]; p = .063). We found no associations between CRP and olfactory change (ps > .368). Sensitivity analyses showed that associations between CRP and olfaction were confined to younger participants (age <= 72 years) and men (ps < .034). Conclusions Our findings suggest a negative association between serum CRP levels and olfactory identification ability in aging that may be dependent on age and sex.

Visual stimuli often dominate nonvisual stimuli during multisensory perception. Evidence suggests higher cognitive processes prioritize visual over nonvisual stimuli during divided attention. Visual stimuli should thus be disproportionally distracting when processing incongruent cross-sensory stimulus pairs. We tested this assumption by comparing visual processing with olfaction, a “primitive” sensory channel that detects potentially hazardous chemicals by alerting attention. Behavioral and event-related brain potentials (ERPs) were assessed in a bimodal object categorization task with congruent or incongruent odor–picture pairings and a delayed auditory target that indicated whether olfactory or visual cues should be categorized. For congruent pairings, accuracy was higher for visual compared to olfactory decisions. However, for incongruent pairings, reaction times (RTs) were faster for olfactory decisions. Behavioral results suggested that incongruent odors interfered more with visual decisions, thereby providing evidence for an “olfactory dominance” effect. Categorization of incongruent pairings engendered a late “slow wave” ERP effect. Importantly, this effect had a later amplitude peak and longer latency during visual decisions, likely reflecting additional categorization effort for visual stimuli in the presence of incongruent odors. In sum, contrary to what might be inferred from theories of “visual dominance,” incongruent odors may in fact uniquely attract mental processing resources during perceptual incongruence.