| Part 1.Prevalence and associated factors of olfactory impairment in ruraldwelling older adultsObjective:Olfactory impairment(OI)refers to decreased(hyposmia)or absent(anosmia)ability to smell.This is the first population-based study of olfactory impairment that targets older adults living in rural communities in western Shandong,China.We sought to estimate the prevalence and correlates of OI among rural-dwelling Chinese older adults.Methods:This population-based cross-sectional analysis included 4,514 participants(age≥65 years;56.7%women)from the Multidomain Interventions to Delay Dementia and Disability in Rural China(MIND-China).The 16-item Sniffin’ Sticks identification test(SSIT)was used to assess olfactory function.Olfactory impairment was defined as the SSIT score ≤10,hyposmia as SSIT score of 8-10,and anosmia as SSIT score<8.Multivariable logistic regression models were used to examine factors associated with OI.Results:The overall prevalence was 67.7%for OI,35.3%for hyposmia,and 32.5%for anosmia.The prevalence increased with age for OI and anosmia,but not for hyposmia.The multivariable-adjusted odds ratio(OR)of OI was 2.10(95%CI 1.69-2.61)for illiteracy and 1.41(1.18-1.70)for elementary school(vs.middle school or above),1.30(1.01-1.67)for current smoking(vs.never smoking),0.86(0.74-0.99)for overweight and 0.73(0.61-0.87)for obesity(vs.normal weight),4.21(2.23-7.94)for dementia,1.68(1.23-2.30)for head injury,and 1.44(1.14-1.83)for sinonasal disease.Illiteracy in combination with either male sex or diabetes was significantly associated with an over two-fold increased OR of OI(p for interactions<0.05).Conclusion:Olfactory impairment is highly prevalent that affects over two-thirds of ruraldwelling older adults in China.OI is correlated with illiteracy,current smoking,dementia,head injury,and sinonasal disease,but negatively associated with overweight or obesity.Olfactory impairment as a potential clinical marker of neurodegenerative disorders among older adults deserves further investigation.Part 2.Correlation between olfactory dysfunction and cognitive function of rural-dwelling older adultsObjective: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).The majority of dementia population live in low-and middle-income countries,where people with dementia are largely overlooked and substantially underdiagnosed,especially among those living in the remote rural areas.In this regard,a brief and reliable tool is crucial for detection of dementia.In this large-scale community-based study,we 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 multi-adjusted 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 logistic model.Hippocampal and entorhinal cortex volumes partly mediated the association between anosmia and MCI.The mediation analysis revealed that the mediation effect of hippocampal volume in the association between anosmia and MCI was 0.04(95%CI 0.00-0.10)and 0.05(0.01-0.11)for entorhinal cortex volume(Figure 3),corresponding to the proportion 6.1%and 8.2%,respectively.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.Part 3 Mechanism between olfactory dysfunction and cognitive function of ruraldwelling older adultsObjective:Olfactory function might be impaired in the early stage of the dementing process,and thus,olfactory test may be useful for identifying elderly persons at an increased risk.However,previous studies that investigate the relationship between olfactory function and cognitive phenotypes have been scarcely conducted among older people living in the rural communities and the associations of olfaction with specific cognitive remains unclear.To investigate the relationships of impaired olfaction with mild cognitive impairment(MCI),global cognitive ability,various domains of cognitive function,and plasma and neuroimaging biomarkers of amyloid pathologies,white matter lesions,and neurodegeneration among Chinese older adults.Methods:This population-based cross-sectional study included 4214 participants(age≥65 years;56.0%women)from MIND-China who were free of dementia and examined in March-September 2018.Olfactory function was assessed using the 16-item Sniffin,Sticks identification test(SSIT).Global cognitive function was evaluated with the Chinese version of the Mini-Mental State Examination(MMSE)and a neuropsychological battery was used to assess memory,language,attention,and executive function.We followed the Petersen’s criteria to define MCI.In subsamples,we measured plasma concentrations of amyloid-β40(Aβ40),Aβ42,total-tau,and neurofilament light chain(NfL)using the Simoa technology(n=1054);and quantified hippocampal volume,entorhinal cortex volume,Alzheimer’s disease-signature cortical thickness,and white matter hyperintensities(WMHs)volume on MRI scans(n=917).Data were analyzed with logistic regression models,general linear regression models and mediation models.Results:Of the 4214 participants,MCI was diagnosed in 1102 persons(26.2%),including 931 with amnestic MCI(aMCI)and 171 with non-amnestic MCI(naMCI).Olfactory impairment(hyposmia and anosmia)was associated with an increased likelihood of MCI,aMCI,and naMCI in a dose-response manner(p for trend<.001).Multiple general linear regression analysis showed that SSIT score was significantly associated with the scores of MMSE test(β coefficient=0.29,95%CI 0.25-0.34),zscore of memory(β coefficient=0.05,95%CI 0.04-0.06),language(βcoefficient=0.05,95%CI 0.04-0.06),and attention(β coefficient=0.04,95%CI 0.04-0.05),and executive function(β coefficient=0.04,95%CI 0.03-0.04).In the plasma biomarker or MRI subsample,anosmia(SSIT score 0-7)was significantly associated with plasma total-tau(demographic-adjusted β=0.26;95%CI=0.12-0.41),and NfL(0.12;0.04-0.19),and hippocampal volume(-0.13;-0.220.04),entorhinal cortex volume(-0.08;-0.13--0.02),and WMHs volume(0.19;0.080.30),and marginally associated with Alzheimer-signature cortical thickness(-0.02;0.05-0.00,p=0.08),but not with plasma Aβ concentrations(p>0.05).Mediation analysis showed that MRI markers including WMHs volume,hippocampal and entorhinal cortex volumes partly mediated the association between anosmia and MCI(12.8%).Discussion:Anosmia is a clinical marker for prodromal dementia.A greater olfactory identification ability is associated with a lower likelihood of MCI,aMCI,naMCI and better performances in global cognitive function,attention,memory,language function and executive function,among Chinese older adults who are living in the rural communities with limited education.Anosmia and MCI in older adults may be linked via common neuropathologies of cerebral white matter lesions and neurodegeneration. |
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