Effect of Neurotoxin Exposure on Blood Biomarkers of Neurodegeneration and Alzheimer Disease.

AIM: To determine whether exposure to neurotoxins in midlife is associated with changes in blood-based biomarkers of neurodegeneration and Alzheimer disease pathology. METHODS: Blood cadmium, lead, neurofilament light (NfL) chain, total tau (TTau), and amyloid beta (Aß) 40 and Aß42 concentrations were measured in 1516 participants in the Beaver Dam Offspring Study. Linear mixed-effect models were used to determine associations between baseline cadmium and lead levels and baseline NfL, TTau, and Aß42/Aß40, and 10-year change in concentrations using repeated measures of these biomarkers as the outcome. RESULTS: In women, higher cadmium and lead levels were associated with higher baseline TTau concentrations. A higher baseline cadmium level was associated with lower baseline Aß42/Aß40 in both men and women. In age-sex-adjusted models, a doubling in baseline cadmium level was associated with a 0.2% (95% CI: 0.0, 0.3) higher increase per year in NfL concentrations. In men, a doubling of baseline lead level was associated with a 0.9% (95% CI: 0.1, 1.7) higher increase per year in TTau concentration. CONCLUSIONS: Participants with relatively higher levels of cadmium and lead had blood biomarker concentrations consistent with more neuronal damage and Alzheimer disease pathology. Environmental exposure to neurotoxins may contribute to neurodegeneration.

Inflammation, metabolic dysregulation and environmental neurotoxins and risk of cognitive decline and impairment in midlife.

BACKGROUND: Age-related declines in cognitive function may begin in midlife. PURPOSE: To determine whether blood-based biomarkers of inflammation, metabolic dysregulation and neurotoxins are associated with risk of cognitive decline and impairment. METHODS: Baseline blood samples from the longitudinal Beaver Dam Offspring Study (2005-2008) were assayed for markers of inflammation, metabolic dysregulation, and environmental neurotoxins. Cognitive function was measured at baseline, 5-year (2010-2013) and 10-year (2015-2017) examinations. Participants without cognitive impairment at baseline and with cognitive data from at least one follow-up were included. Cox proportional hazards models were used to evaluate associations between baseline blood biomarkers and the 10-year cumulative incidence of cognitive impairment. Poisson models were used to estimate the relative risk (RR) of 5-year decline in cognitive function by baseline blood biomarkers. Models were adjusted for age, sex, education, and cardiovascular related risk factors. RESULTS: Participants (N = 2421) were a mean age of 49 years and 55% were women. Soluble vascular cell adhesion molecule-1 (sVCAM-1Tertile(T)3 vs T1-2 hazard ratio (HR) = 1.72, 95% confidence interval (CI) = 1.05,2.82) and hemoglobin A1C (HR = 1.75, 95% CI = 1.18,2.59, per 1% in women) were associated with the 10-year cumulative incidence of cognitive impairment. sVCAM-1 (RRT3 vs T1-2 = 1.45, 95% CI = 1.06,1.99) and white blood cell count (RR = 1.10, 95% CI = 1.02,1.19, per 103/µL) were associated with 5-year cognitive decline. CONCLUSIONS: Biomarkers related to inflammation and metabolic dysregulation were associated with an increased risk of developing cognitive decline and impairment. These results extend previous research in cognitive aging to early markers of cognitive decline in midlife, a time when intervention methods may be more efficacious.

Inflammatory and vascular markers and olfactory impairment in older adults.

BACKGROUND: the incidence of olfactory impairment increases sharply in the eighth and ninth decades of life but the aetiology of age-related olfactory decline is not well understood. Inflammation and atherosclerosis are associated with many age-related conditions and atherosclerosis has been associated with olfactory decline in middle-aged adults. OBJECTIVE: to determine if inflammatory markers and atherosclerosis are associated with the development of olfactory impairment in older adults. DESIGN: longitudinal, population-based study. SETTING/PARTICIPANTS: a total of 1,611 participants, aged 53-97 years in the Epidemiology of Hearing Loss Study without olfactory impairment at the 1998-2000 examination and with follow-up at a subsequent examination 5 and/or 10 years later. METHODS: the San Diego Odor Identification Test was used to measure olfaction. High sensitivity C-reactive protein, interleukin-6 and tumour necrosis factor-α were measured in serum and carotid ultrasound images were obtained for the measurement of carotid intima media thickness (IMT) and plaque assessment. Medical history, behavioural and lifestyle information were obtained by interview. RESULTS: inflammatory markers, IMT and plaque were not associated with the 10-year cumulative incidence of olfactory impairment in adjusted Cox proportional hazard models. Among those <60 years, the mean IMT [hazard ratio (HR) = 4.35, 95% confidence interval (CI) = 1.69-11.21, tertile 3 versus tertile 1] and the number of sites with plaque (HR = 1.56, 95% CI = 1.17-2.08, per site) were associated with an increased risk of developing an olfactory impairment at follow-up. CONCLUSION: subclinical atherosclerosis at a younger age may be a risk factor for the development of olfactory impairment.

Midlife sensory and motor functions improve long-term predictions of cognitive decline and incidence of cognitive impairment.

INTRODUCTION: We aimed to assess whether midlife sensory and motor functions improve risk prediction of 10-year cognitive decline and impairment when added to risk prediction models using the Cardiovascular Risk Factors, Aging, and Incidence of Dementia Score (CAIDE) and Framingham Risk Score (FRS). METHODS: Longitudinal data of N = 1529 (mean age 49 years; 54% women) Beaver Dam Offspring Study (BOSS) participants from baseline, 5 and 10-year follow-up were included. We tested whether including baseline sensory (hearing, vision, olfactory) impairment and motor function improves CAIDE or FRS risk predictions of 10-year cognitive decline or cognitive impairment incidence using logistic regressions. RESULTS: Adding sensory and motor measures to CAIDE-only and FRS-only models significantly improved areas under the curve for cognitive decline and impairment models. DISCUSSION: Including midlife sensory and motor function improved risk predictions of long-term cognitive decline and impairment in middle-aged to older adults. Sensory and motor assessments could contribute to cost-effective and non-invasive screening tools that identify high-risk individuals earlier to target intervention and prevention strategies. Highlights: Sensory and motor measures improve risk prediction models of cognitive decline.Sensory and motor measures improve risk prediction models of cognitive impairment.Prediction improvements were strongest in midlife (adults < 55 years of age).Sensory and motor changes may help identify high-risk individuals early.

Midlife sensory and motor functions improve prediction of blood-based measures of neurodegeneration and Alzheimer's disease in late middle-age.

INTRODUCTION: We assessed whether midlife sensory and motor functions added to prediction models using the Cardiovascular Risk Factors, Aging, and Incidence of Dementia Score (CAIDE) and Framingham Risk Score (FRS) improve risk predictions of 10-year changes in biomarkers of neurodegeneration and Alzheimer's disease. METHODS: Longitudinal data of N = 1529 (mean age 49years) Beaver Dam Offspring Study participants from baseline, 5-year, and 10-year follow-up were included. We tested whether including baseline sensory (hearing, vision, olfactory) impairment and motor function measures improves CAIDE or FRS risk predictions of 10-year incidence of biomarker positivity of serum-based neurofilament light chain (NfL) and amyloid beta (Aß)42/Aß40 using logistic regression. RESULTS: Adding sensory and motor measures to CAIDE-only and FRS-only models significantly improved NfL and Aß42/Aß40 positivity predictions in adults above the age of 55. DISCUSSION: Including midlife sensory and motor function improved long-term biomarker positivity predictions. Non-invasive sensory and motor assessments could contribute to cost-effective screening tools that identify individuals at risk for neurodegeneration early to target interventions and preventions. Highlights: Sensory and motor measures improve risk prediction models of neurodegenerative biomarkersSensory and motor measures improve risk prediction models of AD biomarkersPrediction improvements were strongest in late midlife (adults >55 years of age)Sensory and motor assessments may help identify high-risk individuals early.

Associations of Midlife Lifestyle and Health Factors with Long-Term Changes in Blood-Based Biomarkers of Alzheimer's Disease and Neurodegeneration.

BACKGROUND: Pathological biomarkers of Alzheimer's disease (AD) and other dementias can change decades before clinical symptoms. Lifestyle and health factors might be relevant modifiable risk factors for dementia. Many previous studies have been focusing on associations of lifestyle and health-related factors with clinical outcomes later in life. OBJECTIVE: We aimed to determine to what extent midlife factors of lifestyle, inflammation, vascular, and metabolic health were associated with long-term changes in blood-based biomarkers of AD (amyloid beta (Aß)) and neurodegeneration (neurofilament light chain (NfL); total tau(TTau)). METHODS: In 1,529 Beaver Dam Offspring Study (BOSS) participants (mean age 49 years, standard deviation (SD) = 9; 54% were women), we applied mixed-effects models with baseline risk factors as determinants and 10-year serum biomarker change as outcomes. RESULTS: We found that education and inflammatory markers were associated with levels and/or change over time across all three markers of AD and neurodegeneration in the blood. There were baseline associations of measures of cardiovascular health with lower Aß42/Aß40. TTau changed little over time and was higher in individuals with diabetes. Individuals with lower risk in a number of cardiovascular and metabolic risk factors, including diabetes, hypertension, and atherosclerosis had slower accumulation of neurodegeneration over time, as determined by NfL levels. CONCLUSION: Various lifestyle and health factors, including education and inflammation, were associated with longitudinal changes of neurodegenerative and AD biomarker levels in midlife. If confirmed, these findings could have important implications for developing early lifestyle and health interventions that could potentially slow processes of neurodegeneration and AD.

Effect of Long-Term Storage on the Reliability of Blood Biomarkers for Alzheimer's Disease and Neurodegeneration.

BACKGROUND: Stored blood samples from longitudinal cohort studies may be useful for studying biomarkers of preclinical Alzheimer's disease. OBJECTIVE: This study aimed to determine the reliability of amyloid-ß40 and amyloid-ß42 (Aß40, Aß42), total tau (TTau), and neurofilament light (NfL) concentrations measured in blood samples stored long-term at -80°C. METHODS: Aß40, Aß42, TTau, and NfL were measured in serum and plasma samples from two longitudinal cohort studies. Serum samples had been stored at -80°C for 5 (n = 24), 14 (n = 24), and 20 years (N = 78) and plasma samples had been stored for 16 years (N = 78). Biomarker concentrations were measured in duplicate using a single molecule array assay (Simoa; Quanterix, Billerica, MA). Replicate samples for each sample type and storage length were included. RESULTS: The concentrations of Aß40, Aß42, TTau, and NfL were within expected ranges. Some serum TTau concentrations were below the limit of detection. The average intra-assay coefficients of variation (CV) for duplicate measures were 2-7% for all assays except for serum TTau, which were higher (CVs 13% and 17%). Mean differences in original replicate pair Aß40, Aß42, and NfL concentrations were slightly greater in samples stored for longer versus shorter time periods. CONCLUSION: Aß40, Aß42, TTau, and NfL can be measured in serum and plasma samples that have been stored up to 20 years at -80°C. Long-term storage may be associated with small increases in the variability of concentrations in samples stored 14 or more years.

Better cognitive function in younger generations - Insights from two cohort studies of middle-aged to older adults in Wisconsin.

BACKGROUND: Understanding generational trends in dementia and cognitive decline is essential to quantify future healthcare needs and may help identify interventions and preventions. We aimed to determine whether individuals from more recent generations showed better neurocognitive function. METHODS: This cross-sectional study combined data from 4439 participants (mean age 64 years (SD = 13); 57% were women) from the Epidemiology of Hearing Loss Study and Beaver Dam Offspring Study. We assessed participants' birth cohort (1901-1924, Greatest Generation; 1925-1945, Silent Generation; 1946-1964, Baby Boom Generation; 1965-1984, Generation X) and neurocognition (Trail-Making Tests A and B, Digit Symbol Substitution Test, Auditory Verbal Learning Test, Verbal Fluency Test). Multivariable linear regression models were utilized. RESULTS: Adjusted for age, sex, education, and known risk factors for cognitive decline, more recent generations showed better processing speed, executive function, attention, and verbal fluency than the Greatest Generation. Largest benefits were found in the Baby Boom Generation. Compared with the Greatest Generation, individuals from the Baby Boom Generation performed better on Trail-Making Tests A (-0.21 ln(time in s); 95% confidence interval (CI) -0.29, -0.13) and B (-0.31 ln(time in s); 95% CI -0.40, -0.22), Digit Symbol Substitution Test (6.07 numbers correct; 95% CI 3.61, 8.52) and Verbal Fluency Test (8.75 numbers correct; 95% CI 5.07, 12.42 in women; 5.28 numbers correct; 95% CI 0.79, 9.78 in men), with effect sizes similar to effects of 11-15 years of less aging. CONCLUSIONS: This indicates that some benefits of younger generations might be related to yet unknown and potentially modifiable environmental, health-related or lifestyle factors and motivates research of such underlying factors to promote healthy cognitive aging.

Exposure to Cadmium, Lead, and Tobacco Smoke and the 10-Year Cumulative Incidence of Olfactory Impairment: The Beaver Dam Offspring Study.

Importance: Olfactory impairment is common in older adults. Identification of modifiable risk factors for olfactory impairment at midlife has the potential to reduce the burden of olfactory impairment at older ages. Objective: To determine the 10-year cumulative incidence of olfactory impairment and evaluate potentially modifiable risk factors for impairment including exposure to cadmium, lead, and tobacco smoke. Design, Setting, and Participants: Data from the Beaver Dam Offspring Study, a longitudinal cohort study of sensory health and aging in a general population, were available from examinations at baseline (2005-2008), 5 years (2010-2013), and 10 (2015-2017) years. A total of 2312 participants without olfactory impairment at baseline and with olfaction data available at the 5- and/or 10-year examination were included. The present study was conducted from April 28, 2020, to January 8, 2021. Main Outcomes and Measures: Olfactory impairment was measured by the San Diego Odor Identification Test. Cox discrete-time proportional hazards analyses were used to model associations between baseline covariates, including blood cadmium and lead levels and tobacco smoke exposure, and the 10-year cumulative incidence of olfactory impairment. Results: Of the 2312 participants, 1269 (54.9%) were women; mean age was 49 years (range, 22-84 years) at baseline. The 10-year cumulative incidence of olfactory impairment was 4.6% (95% CI, 3.7%-5.6%) and increased with age. Because of high collinearity, cadmium and tobacco smoke exposure were modeled separately. In a multivariable adjusted model, higher blood cadmium level (hazard ratio [HR], 1.70; 95% CI, 1.05-2.74) was associated with the 10-year cumulative incidence of olfactory impairment. Substituting tobacco smoke exposure for cadmium in the model, high exposure to tobacco smoke as a current smoker (HR, 2.94; 95% CI, 1.63-5.29, smoker vs no exposure) or from environmental tobacco smoke (HR, 2.65; 95% CI, 1.24-5.63, high vs no exposure) was also associated with an increased risk for developing olfactory impairment. Blood lead levels were not associated with olfactory impairment. Conclusions and Relevance: Results of this longitudinal cohort study suggest that modifiable environmental exposures may contribute to olfactory impairment that occurs with aging. Identification of modifiable risk factors for olfactory impairment may lead to prevention strategies that have the potential to reduce the burden of olfactory impairment at older ages.

Macular Ganglion Cell-Inner Plexiform Layer as a Marker of Cognitive and Sensory Function in Midlife.

BACKGROUND: Neurodegenerative diseases are public health challenges in aging populations. Early identification of people at risk for neurodegeneration might improve targeted treatment. Noninvasive, inexpensive screening tools are lacking but are of great potential. Optical coherence tomography (OCT) measures the thickness of nerve cell layers in the retina, which is an anatomical extension of the brain and might be indicative of common underlying neurodegeneration. We aimed to determine the association of macular ganglion cell-inner plexiform layer (mGCIPL) thickness with cognitive and sensorineural function in midlife. METHOD: This cross-sectional study included 1,880 Beaver Dam Offspring Study participants (aged 27-93 years, mean 58) who participated in the 10-year follow-up examination. We assessed cognitive function and impairment, hearing sensitivity thresholds and impairment, central auditory processing, visual impairment, and olfactory impairment. We measured mGCIPL using the Cirrus 5000 HD-OCT Macular Cube Scan. Multivariable linear and logistic regression models adjusted for potential confounders were used to determine associations between mGCIPL thickness and cognitive and sensorineural functions, as well as for comparing participants with a thin mGCIPL (1 SD below average) to the remainder in those functions. RESULTS: Thinner mGCIPL was associated with worse cognitive function, worse central auditory function, and visual impairment. We found an association of mGCIPL thickness with hearing sensitivity in women only and no association with impairment in hearing, olfaction, and cognition. Results on the thin group comparisons were consistent. CONCLUSIONS: mGCIPL thickness is associated with cognitive and sensorineural function and has the potential as a marker for neurodegeneration in middle-aged adults.

Brain Aging in Midlife: The Beaver Dam Offspring Study.

OBJECTIVES: Middle age has been identified as a critical time period for health later in life. Identifying factors associated with worse brain function in middle-aged adults may help identify ways to preserve brain function with aging. Our objective was to evaluate factors associated with a novel measure of brain aging in middle-aged and older adults. DESIGN: Longitudinal cohort study. SETTING: Beaver Dam Offspring Study (BOSS) baseline (2005-2008), 5-year (2010-2013), and 10-year examinations (2015-2017). PARTICIPANTS: A total of 2285 adults, 22 to 84 years of age, with complete sensorineural and neurocognitive data at the 5-year examination. MEASUREMENTS: Principal component analysis (PCA) was performed combining 5-year sensorineural (hearing, vision, olfaction) and cognitive (Trail Making Test A and B, Digit Symbol Substitution Test, Verbal Fluency Test, Auditory Verbal Learning Test) test data. Participants with a standardized PCA score less than -1 were classified as having brain aging. Incident brain aging was defined as a PCA score less than -1 at 10 years among participants who had a PCA score of -1 or higher at 5 years. Logistic regression and Poisson models were used to estimate associations between baseline factors and prevalent or incident brain aging, respectively. RESULTS: Older age, being male, current smoking, larger waist circumference, not consuming alcohol, cardiovascular disease, and interleukin-6 were associated with greater odds of prevalent brain aging, whereas more education and exercise were associated with decreased odds. In addition to age and sex, less than a college education, higher levels of soluble intercellular adhesion molecule-1, diabetes, depressive symptoms, and history of head injury were associated with an increased 5-year risk of incident brain aging. CONCLUSION: In the current study, vascular and inflammatory factors were associated with a new brain aging marker in middle-aged and older adults. Many of these factors are modifiable, highlighting the importance of addressing health and lifestyle factors in midlife to potentially preserve function for better brain health later in life. J Am Geriatr Soc 67:1610-1616, 2019.

Sensorineural Impairments, Cardiovascular Risk Factors, and 10-Year Incidence of Cognitive Impairment and Decline in Midlife: The Beaver Dam Offspring Study.

BACKGROUND: Sensorineural impairments and cardiovascular risk factors (CVRF) and disease (CVD) in midlife may be important predictors of future cognitive health, but longitudinal studies that include multiple sensorineural measures in middle-aged adults are lacking. METHODS: Hearing, vision, and olfaction, and CVRF and CVD were measured at the Beaver Dam Offspring Study baseline (2005-2008) examination. The Mini-Mental State Examination and Trail Making Tests A and B were administered at all phases and additional cognitive function measures were obtained at 5 (2010-2013) and 10 years (2015-2017). Cox proportional hazards models were used to evaluate associations between baseline sensorineural impairments, CVRF, CVD, and 10-year cumulative incidence of cognitive impairment and decline. RESULTS: There were 2,556 participants (22-84 years) without cognitive impairment at baseline and data from at least one follow-up. In a multivariable model including age, sex, education, and head injury, visual impairment (hazard ratio = 2.59, 95% confidence interval = 1.34, 5.02), olfactory impairment (hazard ratio = 3.18, 95% confidence interval = 1.53, 6.59), CVD (hazard ratio = 2.37, 95% confidence interval = 1.24, 4.52), and not consuming alcohol in the past year (hazard ratio = 2.21, 95% confidence interval = 1.16, 4.19) were associated with the 10-year cumulative incidence of cognitive impairment. Current smoking and diabetes were associated with increased risk, and exercise with decreased risk, of 10-year decline in cognitive function. CONCLUSIONS: Visual and olfactory impairments, CVRF, and CVD were associated with the 10-year cumulative incidence of cognitive impairment and decline in middle-aged adults. Identifying modifiable factors associated with cognitive decline and impairment in midlife may provide opportunities for prevention or treatment and improve cognitive health later in life.

Odor detection thresholds in a population of older adults.

OBJECTIVES/HYPOTHESIS: To measure odor detection thresholds and associated nasal and behavioral factors in an older adult population. STUDY DESIGN: Cross-sectional cohort study. METHODS: Odor detection thresholds were obtained using an automated olfactometer on 832 participants, aged 68 to 99 (mean age = 77) years in the 21-year (2013-2016) follow-up visit of the Epidemiology of Hearing Loss Study. RESULTS: The mean odor detection threshold (ODT) score was 8.2 (range = 1-13; standard deviation = 2.54), corresponding to an n-butanol concentration of slightly less than 0.03%. Older participants were significantly more likely to have lower (worse) ODT scores than younger participants (P < .001). There were no significant differences in mean ODT scores between men and women. Older age was significantly associated with worse performance in multivariable regression models, and exercising at least once per week was associated with reduced odds of having a low (≤5) ODT score. Cognitive impairment was also associated with poor performance, whereas a history of allergies or a deviated septum was associated with better performance. CONCLUSIONS: Odor detection threshold scores were worse in older age groups but similar between men and women in this large population of older adults. Regular exercise was associated with better odor detection thresholds, adding to the evidence that decline in olfactory function with age may be partly preventable. LEVEL OF EVIDENCE: 3b. Laryngoscope, 127:1257-1262, 2017.

Sensory Impairments and Risk of Mortality in Older Adults.

BACKGROUND: Sensory impairments increase with age and the majority of older people will experience a sensory impairment if they live long enough. However, the relationships of hearing, visual, and olfactory impairments with mortality are not well understood. METHODS: Epidemiology of Hearing Loss Study participants (n = 2,418) aged 53-97 years (mean = 69 years) were examined in 1998-2000 and hearing, visual acuity, and olfaction were measured. Participants were followed for mortality for up to 17 years (mean = 12.8 years). Cox proportional hazards models were used to assess the association between prevalent sensory impairments and the 15-year cumulative incidence of death. RESULTS: A total of 1,099 (45.4%) of participants died during the follow-up period. In age- and sex-adjusted Cox models, the risk of mortality was higher among participants with one (hazard ratio [HR] = 1.40, 95% confidence interval [CI] = 1.19, 1.64) or two or more (HR = 2.12, 95% CI = 1.74, 2.58) sensory impairments than among participants with no sensory impairments. Olfactory impairment at baseline was significantly associated with mortality (HR = 1.28, 95% CI = 1.07, 1.52) after adjusting for age, sex, sensory comorbidities, cardiovascular risk factors and disease, cognitive impairment, frailty, subclinical atherosclerosis, and inflammatory marker levels (n = 1,745). Hearing and visual impairment were not associated with mortality after adjusting for subclinical atherosclerosis and inflammation. CONCLUSION: Olfactory impairment, but not hearing or visual impairment, was associated with an increased risk of mortality. These results suggest that olfactory impairment may be a marker of underlying physiologic processes or pathology that is associated with aging and reduced survival in older adults.

Sensory Impairments and Cognitive Function in Middle-Aged Adults.

BACKGROUND: Hearing, visual, and olfactory impairments have been associated with cognitive impairment in older adults but less is known about associations with cognitive function in middle-aged adults. METHODS: Sensory and cognitive functions were measured on participants in the baseline examination (2005-2008) of the Beaver Dam Offspring Study. Cognitive function was measured with the Trail Making tests A (TMTA) and B (TMTB) and the Grooved Peg Board test. Pure-tone audiometry, Pelli-Robson letter charts, and the San Diego Odor Identification test were used to measure hearing, contrast sensitivity, and olfaction, respectively. RESULTS: There were 2,836 participants aged 21-84 years with measures of hearing, visual, olfactory, and cognitive function at the baseline examination. Nineteen percent of the cohort had one sensory impairment and 3% had multiple sensory impairments. In multivariable adjusted linear regression models that included all three sensory impairments, hearing impairment, visual impairment, and olfactory impairment were each independently associated with poorer performance on the TMTA, TMTB, and Grooved Peg Board (p < .05 for all sensory impairments in all models). Participants with a sensory impairment took on average from 2 to 10 seconds longer than participants without the corresponding sensory impairment to complete these tests. Results were similar in models that included adjustment for hearing aid use. CONCLUSION: Hearing, visual and olfactory impairment were associated with poorer performance on cognitive function tests independent of the other sensory impairments and factors associated with cognition. Sensory impairments in midlife are associated with subtle deficits in cognitive function which may be indicative of early brain aging.

Carotid Intima Media Thickness, Atherosclerosis, and 5-Year Decline in Odor Identification: The Beaver Dam Offspring Study.

BACKGROUND: The purpose of this study was to determine if subclinical markers of atherosclerosis are associated with a decline in olfactory function. METHODS: The San Diego Odor Identification Test was administered to 2,302 participants (age 21-84 years) at the baseline (2005-2008) and 5-year follow-up (2010-2013) examinations of the Beaver Dam Offspring Study. A decline in odor identification was defined as a decrease in San Diego Odor Identification Test score of 2 or more (range 0-8) from Beaver Dam Offspring Study 1 to Beaver Dam Offspring Study 2. Carotid intima media thickness and plaque, blood pressure, pulse wave velocity, and body mass index were measured and other risk factor data were obtained by interview. RESULTS: Overall 3.2% of participants had a decline in San Diego Odor Identification Test score at 5 years. In age- and sex-adjusted models, mean intima media thickness (odds ratio = 1.17, 95% CI = 1.01, 1.34, per 0.1 mm) and number of sites (range 0-6) with carotid artery plaque (odds ratio = 1.35, 95% CI = 1.11, 1.65, per site) at baseline were associated with an increased risk for decline. Plaque score (odds ratio = 1.24, 95% CI = 1.01, 1.53) remained a significant independent predictor of olfactory decline in a model that included age, sex, hypertension, body mass index, alcohol, and smoking. CONCLUSIONS: Subclinical atherosclerosis was associated with an increased risk for olfactory decline indicating that atherosclerosis may be one of the risk factors for the decline in olfactory function seen with aging. Strategies to improve vascular health may also benefit olfactory health.