BACKGROUND

The objective of this study was to establish a prospective population-based cohort to investigate the prevalence, incidence and risk factors for mild cognitive impairment (MCI) and dementia.

METHODS

The Olmsted County, Minn., population, aged 70-89 years on October 1, 2004, was enumerated using the Rochester Epidemiology Project. Eligible subjects were randomly selected and invited to participate. Participants underwent a comprehensive in-person evaluation including the Clinical Dementia Rating Scale, a neurological evaluation and neuropsychological testing. A consensus diagnosis of normal cognition, MCI or dementia was made by a panel using previously published criteria. A subsample of subjects was studied via telephone interview.

RESULTS

Four hundred and two subjects with dementia were identified from a detailed review of their medical records but were not contacted. At baseline, we successfully evaluated 703 women aged 70-79 years, 769 women aged 80-89 years, 730 men aged 70-79 years and 517 men aged 80-89 years (total n = 2,719). Among the participants, 2,050 subjects were evaluated in person and 669 via telephone.

CONCLUSIONS

Strengths of the study are that the subjects were randomly selected from a defined population, the majority of the subjects were examined in person, and MCI was defined using published criteria. Here, we report the design and sampling, participation, baseline measures and sample characteristics.

OBJECTIVE

We investigated the prevalence of mild cognitive impairment (MCI) in Olmsted County, MN, using in-person evaluations and published criteria.

METHODS

We evaluated an age- and sex-stratified random sample of Olmsted County residents who were 70-89 years old on October 1, 2004, using the Clinical Dementia Rating Scale, a neurologic evaluation, and neuropsychological testing to assess 4 cognitive domains: memory, executive function, language, and visuospatial skills. Information for each participant was reviewed by an adjudication panel and a diagnosis of normal cognition, MCI, or dementia was made using published criteria.

RESULTS

Among 1,969 subjects without dementia, 329 subjects had MCI, with a prevalence of 16.0% (95% confidence interval [CI] 14.4-17.5) for any MCI, 11.1% (95% CI 9.8-12.3) for amnestic MCI, and 4.9% (95% CI 4.0-5.8) for nonamnestic MCI. The prevalence of MCI increased with age and was higher in men. The prevalence odds ratio (OR) in men was 1.54 (95% CI 1.21-1.96; adjusted for age, education, and nonparticipation). The prevalence was also higher in subjects who never married and in subjects with an APOE epsilon3epsilon4 or epsilon4epsilon4 genotype. MCI prevalence decreased with increasing number of years of education (p for linear trend <0.0001).

CONCLUSIONS

Our study suggests that approximately 16% of elderly subjects free of dementia are affected by MCI, and amnestic MCI is the most common type. The higher prevalence of MCI in men may suggest that women transition from normal cognition directly to dementia at a later age but more abruptly.

BACKGROUND

Physical exercise is associated with decreased risk of dementia and Alzheimer disease.

OBJECTIVE

To investigate whether physical exercise is associated with decreased risk of mild cognitive impairment (MCI).

METHODS

Population-based case-control study.

METHODS

The Mayo Clinic Study of Aging, an ongoing population-based cohort study in Olmsted County, Minnesota.

METHODS

A total of 1324 subjects without dementia who completed a Physical Exercise Questionnaire.

METHODS

An expert consensus panel classified each subject as having normal cognition or MCI based on published criteria.

RESULTS

We compared the frequency of physical exercise among 198 subjects with MCI with that among 1126 subjects with normal cognition and adjusted the analyses for age, sex, years of education, medical comorbidity, and depression. The odds ratios for any frequency of moderate exercise were 0.61 (95% confidence interval, 0.43-0.88; P = .008) for midlife (age range, 50-65 years) and 0.68 (95% confidence interval, 0.49-0.93; P = .02) for late life. The findings were consistent among men and women. Light exercise and vigorous exercise were not significantly associated with decreased risk of MCI.

CONCLUSIONS

In this population-based case-control study, any frequency of moderate exercise performed in midlife or late life was associated with a reduced odds of having MCI.

BACKGROUND

The association between gait speed and cognition has been reported; however, there is limited knowledge about the temporal associations between gait slowing and cognitive decline among cognitively normal individuals.

METHODS

The Mayo Clinic Study of Aging is a population-based study of Olmsted County, Minnesota, United States, residents aged 70-89 years. This analysis included 1,478 cognitively normal participants who were evaluated every 15 months with a nurse visit, neurologic evaluation, and neuropsychological testing. The neuropsychological battery used nine tests to compute domain-specific (memory, language, executive function, and visuospatial skills) and global cognitive z-scores. Timed gait speed (m/s) was assessed over 25 feet (7.6 meters) at a usual pace. Using mixed models, we examined baseline gait speed (continuous and in quartiles) as a predictor of cognitive decline and baseline cognition as a predictor of gait speed changes controlling for demographics and medical conditions.

RESULTS

Cross-sectionally, faster gait speed was associated with better performance in memory, executive function, and global cognition. Both cognitive scores and gait speed declined over time. A faster gait speed at baseline was associated with less cognitive decline across all domain-specific and global scores. These results were slightly attenuated after excluding persons with incident mild cognitive impairment or dementia. By contrast, baseline cognition was not associated with changes in gait speed.

CONCLUSIONS

Our study suggests that slow gait precedes cognitive decline. Gait speed may be useful as a reliable, easily attainable, and noninvasive risk factor for cognitive decline.

BACKGROUND

The telephone assessment of cognitive functions may reduce the cost and burden of epidemiological studies.

METHODS

We validated the Telephone Interview for Cognitive Status-modified (TICS-m) using an extensive in-person assessment as the standard for comparison. Clinical diagnoses of normal cognition, mild cognitive impairment (MCI), or dementia were established by consensus of physician, nurse, and neuropsychological assessments.

RESULTS

The extensive in-person assessment classified 83 persons with normal cognition, 42 persons with MCI, and 42 persons with dementia. There was considerable overlap in TICS-m scores among the three groups. Receiver operating characteristic curves identified < or = 31 as the optimal cutoff score to separate subjects with MCI from subjects with normal cognition (sensitivity = 71.4%; subjects with dementia excluded), and < or = 27 to separate subjects with dementia from subjects with MCI (sensitivity = 69.0%; subjects with normal cognition excluded). The TICS-m performed well when subjects with MCI were pooled either with subjects with dementia (sensitivity = 83.3%) or with subjects with normal cognition (sensitivity = 83.3%).

CONCLUSIONS

Although the TICS-m performed well when using a dichotomous classification of cognitive status, it performed only fairly in separating MCI from either normal cognition or dementia. The TICS-m should not be used as a free-standing tool to identify subjects with MCI, and it should be used with caution as a tool to detect dementia.

BACKGROUND

Although data from rodent systems are extremely useful in providing insights into possible mechanisms of age-related bone loss, concepts evolving from animal models need to ultimately be tested in humans.

METHODS

This review provides an update on mechanisms of age-related bone loss in humans based on the author's knowledge of the field and focused literature reviews.

RESULTS

Novel imaging, experimental models, biomarkers, and analytic techniques applied directly to human studies are providing new insights into the patterns of bone mass acquisition and loss as well as the role of sex steroids, in particular estrogen, on bone metabolism and bone loss with aging in women and men. These studies have identified the onset of trabecular bone loss at multiple sites that begins in young adulthood and remains unexplained, at least based on current paradigms of the mechanisms of bone loss. In addition, estrogen appears to be a major regulator of bone metabolism not only in women but also in men. Studies assessing mechanisms of estrogen action on bone in humans have identified effects of estrogen on RANKL expression by several different cell types in the bone microenvironment, a role for TNF-α and IL-1β in mediating effects of estrogen deficiency on bone, and possible regulation of the Wnt inhibitor, sclerostin, by estrogen.

CONCLUSIONS

There have been considerable advances in our understanding of age-related bone loss in humans. However, there are also significant gaps in knowledge, particularly in defining cell autonomous changes in bone in human studies to test or validate concepts emerging from studies in rodents. Decision Editor: Luigi Ferrucci, MD, PhD.

OBJECTIVE

Rapid eye movement sleep behavior disorder (RBD) is associated with neurodegenerative disease and particularly with the synucleinopathies. Convenience samples involving subjects with idiopathic RBD have suggested an increased risk of incident mild cognitive impairment (MCI), dementia (usually dementia with Lewy bodies), and Parkinson disease (PD). There are no data on such risks in a population-based sample.

METHODS

Cognitively normal subjects aged 70 to 89 years in a population-based study of aging who screened positive for probable RBD using the Mayo Sleep Questionnaire were followed at 15-month intervals. In a Cox proportional hazards model, we measured the risk of developing MCI, dementia, and PD among the exposed (probable RBD [pRBD](+)) and unexposed (pRBD(-)) cohorts.

RESULTS

Forty-four subjects with pRBD(+) status at enrollment (median duration of pRBD features was 7.5 years) and 607 pRBD(-) subjects were followed prospectively for a median of 3.8 years. Fourteen of the pRBD(+) subjects developed MCI, and 1 developed PD (15/44 = 34% developed MCI/PD); none developed dementia. After adjustment for age, sex, education, and medical comorbidity, pRBD(+) subjects were at increased risk of MCI/PD (hazard ratio [HR], 2.2; 95% confidence interval [CI], 1.3-3.9; p = 0.005). Inclusion of subjects who withdrew from the study produced similar results, as did exclusion of subjects with medication-associated RBD. Duration of pRBD symptoms did not predict the development of MCI/PD (HR, 1.05 per 10 years; 95% CI, 0.84-1.3; p = 0.68).

CONCLUSIONS

In this population-based cohort study, we observed that pRBD confers a 2.2-fold increased risk of developing MCI/PD over 4 years.

OBJECTIVE

To investigate associations of the Mediterranean diet (MeDi) components and the MeDi score with mild cognitive impairment (MCI).

METHODS

Participants (aged 70-89 years) were clinically evaluated to assess MCI and dementia, and completed a 128-item food frequency questionnaire.

RESULTS

163 of 1,233 nondemented persons had MCI. The odds ratio of MCI was reduced for high vegetable intake [0.66 (95% CI = 0.44-0.99), p = 0.05] and for high mono- plus polyunsaturated fatty acid to saturated fatty acid ratio [0.52 (95% CI = 0.33-0.81), p = 0.007], adjusted for confounders. The risk of incident MCI or dementia was reduced in subjects with a high MeDi score [hazard ratio = 0.75 (95% CI = 0.46-1.21), p = 0.24].

CONCLUSIONS

Vegetables, unsaturated fats, and a high MeDi score may be beneficial to cognitive function.

The progression of amnestic mild cognitive impairment (a-MCI) to Alzheimer's disease and hypothesized progression of non-amnestic mild cognitive impairment (na-MCI) to non-degenerative or vascular dementias suggest etiologic differences. We examined the association between coronary heart disease (CHD) and mild cognitive impairment (MCI) subtypes in a population-based cohort. Participants (n=1969; aged 70-89 years) were evaluated using the Clinical Dementia Rating Scale, a neurological examination, and neuropsychological testing for diagnoses of normal cognition, MCI, or dementia. CHD was defined as a history of myocardial infarction, angina, angiographic coronary stenosis, or coronary revascularization and ascertained by participant interview and from medical records. CHD was significantly associated with na-MCI (OR=1.93; 95% CI=1.22-3.06) but not with a-MCI (OR=0.94; 95% CI=0.69-1.28). In contrast, ApoE ɛ4 allele was significantly associated with a-MCI (OR=1.75; 95% CI=1.28-2.41), but not with na-MCI (OR=1.17; 95% CI=0.69-2.00). The association of CHD with prevalent na-MCI but not with a-MCI suggests that CHD and na-MCI may have similar underlying etiologies.

BACKGROUND

Defining the nature of the contribution of stroke to cognitive impairment remains challenging.

OBJECTIVE

To describe associations between stroke history, APOE genotype, and subtypes of mild cognitive impairment (MCI).

METHODS

We randomly selected residents from Olmsted County, Minnesota, aged 70 to 89 years on October 1, 2004, and invited eligible subjects without documented dementia to participate. Participants (n = 2050) were evaluated through an informant interview, a neurological evaluation, and neuropsychological testing. Neuropsychological testing included 9 tests to assess memory, attention, executive function, visuospatial cognition, and language. Subjects were diagnosed by consensus as cognitively normal or as having MCI (either amnestic or nonamnestic) or dementia. A history of stroke was obtained from the subjects and confirmed in their medical records. We computed the odds ratios (ORs) for a clinical diagnosis of MCI or for scoring in the lowest quartile on each cognitive domain.

RESULTS

There were 1640 cognitively normal subjects and 329 subjects with MCI: 241 with amnestic MCI and 88 with nonamnestic MCI. In fully adjusted models with only subjects without dementia, a history of stroke was associated with a higher OR of nonamnestic MCI (OR, 2.85; 95% confidence interval [CI], 1.61-5.04) than amnestic MCI (OR, 1.77; 95% CI, 1.14-2.74). A history of stroke was also associated with impaired function in each cognitive domain except memory. The association was strongest for attention and executive function (OR, 2.48; 95% CI, 1.73-3.53). APOE epsilon4 genotype was associated only with amnestic MCI and with impaired memory function.

CONCLUSIONS

In this population-based sample of persons without dementia, a history of stroke was particularly associated with nonamnestic MCI and impairment in nonmemory cognition. The APOE epsilon4 genotype was associated with memory impairment and amnestic MCI.

Dysfunctional insulin signaling may affect brain metabolism or amyloid deposition. We investigated the associations of type 2 diabetes with amyloid accumulation measured using (11)C-Pittsburgh compound B ((11)C-PiB) and brain hypometabolism measured using (18)F-FDG PET.

METHODS

We studied a sample of nondemented participants from the population-based Mayo Clinic Study of Aging. All subjects underwent MR imaging, amyloid PET, and (18)F-FDG PET. Alzheimer disease (AD) signature and region-of-interest (ROI) measures for (11)C-PiB retention ratio and (18)F-FDG ratio were measured. Diabetes was assessed from the Rochester Epidemiology Project medical records linkage system.

RESULTS

Among 749 participants (median age, 79.0 y; 56.5% men, 81.0% cognitively normal; 20.6% diabetic individuals), (18)F-FDG hypometabolism ((18)F-FDG ratio < 1.31) in the AD signature meta-ROI was more common in diabetic individuals (48.1%) than in nondiabetic individuals (28.9%; P < 0.001). The median (18)F-FDG ratio was lower in diabetic individuals than in nondiabetic individuals in the AD signature meta-ROI (1.32 vs. 1.40, P < 0.001) and in the angular (1.40 vs. 1.48, P < 0.001) and posterior cingulate gyri ROIs (1.63 vs. 1.72, P < 0.001). The odds ratio (OR) for abnormal AD signature (18)F-FDG hypometabolism was elevated (2.28; 95% confidence interval [CI], 1.56-3.33) in diabetic individuals versus nondiabetic individuals after adjustment for age, sex, and education and after additional adjustment for apolipoprotein ε4 allele, glycemic level, and cognitive status (OR, 1.69; 95% CI, 1.10-2.60). However, the AD signature (11)C-PiB retention ratio was similar in diabetic individuals versus nondiabetic individuals (OR, 1.03; 95% CI, 0.71-1.51; P = 0.87). In post hoc analyses in nondiabetic individuals, a 1% increase in hemoglobin A1c was associated with greater AD signature hypometabolism in cognitively normal subjects (OR, 1.93; 95% CI, 1.03-3.62; P = 0.04) and in the total cohort (OR 1.59; 95% CI, 0.92-2.75; P = 0.10).

CONCLUSIONS

Diabetes and poor glycemic control in nondiabetic individuals may enhance glucose hypometabolism in AD signature regions. These factors should be investigated in longitudinal studies for their role in detecting onset of symptoms in AD.

OBJECTIVE

To investigate the association of chronic obstructive pulmonary disease (COPD) with mild cognitive impairment (MCI) and MCI subtype: amnestic MCI and nonamnestic MCI, in a population-based study of elderly patients.

METHODS

Participants included 1927 individuals aged 70 to 89 years enrolled in the population-based Mayo Clinic Study of Aging. Participants were evaluated by using a nurse assessment, neurological evaluation, and neuropsychological testing, and the diagnosis of MCI was made by a consensus panel according to the standardized criteria. Chronic obstructive pulmonary disease was identified by the review of medical records. The study was conducted from October 1, 2004, through July 31, 2007. The associations of COPD and disease duration with MCI and its subtypes were evaluated by using logistic regression models adjusted for potential covariates.

RESULTS

Of 1927 participants, 288 had COPD (men vs women: 18% vs 12%; P<.001). As compared with patients without COPD, patients with COPD had a higher prevalence of MCI (27% vs 15%; P<.001). The odds ratio (OR) for MCI was almost 2 times higher in patients with COPD than in those without (OR, 1.87; 95% CI, 1.34-2.61), with a similar effect in men and women. The OR for MCI increased from 1.60 (95% CI, 0.97-2.57) in patients with a COPD duration of 5 years or less to 2.10 (95% CI, 1.38-3.14) in patients with a COPD duration of more than 5 years.

CONCLUSIONS

This population-based study suggests that COPD is associated with increased odds of having MCI and its subtypes. There was a dose-response relationship with the duration of COPD after controlling for the potential covariates.

Precise immunological aspects of inflamed gingival mucosa remain to be elucidated in the murine experimental periodontitis model; therefore, we have characterized the mucosal immune cells in the inflamed gingiva of mice with alveolar bone reduction. Mice were orally infected with Porphyromonas gingivalis 15 times over 2 weeks. Gingival mononuclear cells (GMCs) were isolated from P. gingivalis- and sham-infected mice 1, 7, 15, and 30 days after the last infection. Although the greatest degree of periodontitis was seen in P. gingivalis-infected mice at 30 days after infection, the highest levels of IL-6 and TNF-α production were noted in the GMCs isolated 7 days after infection. Further, the frequency of RANKL(+)CD4(+) T-cells in GMCs of inflamed gingiva peaked 15 days after infection. Importantly, the number of Foxp3(+)CD4(+) CD25(+) regulatory T (Treg)-cells was increased only in the experimental group 30 days after infection. Thus, intracellular cytokine analysis revealed an increased number of IL-10-producing CD4(+) T-cells in inflamed gingiva when compared with the control group. These results suggest that there are potential roles for Treg cells during the chronic stage of periodontitis in the regulation of gingival inflammation and alveolar bone loss.

Mono- and polyunsaturated fatty acids (MUFA, PUFA) have been associated with a reduced risk of dementia. The association of these fatty acids with mild cognitive impairment (MCI) is not fully established. The objective of the study was to investigate the cross-sectional association of dietary fatty acids with MCI in a population-based sample. Participants aged>>or= 70 years on October 1, 2004, were evaluated using the Clinical Dementia Rating Scale (participant and informant), a neurological evaluation, and neuropsychological testing. A panel of nurses, physicians, and neuropsychologists reviewed the data for each participant in order to establish a diagnosis of MCI, normal cognition, or dementia by consensus. Participants also completed a 128-item food-frequency questionnaire. Among 1,233 non-demented subjects, 163 (13.2%) had MCI. The odds ratio (OR) of MCI decreased with increasing PUFA and MUFA intake. Compared to the lowest tertile, the OR (95% confidence interval) for the upper tertiles were 0.44 (0.29-0.66; p for trend = 0.0004) for total PUFA; 0.44 (0.30-0.67; p for trend = 0.0004) for omega-6 fatty acids; 0.62 (0.42-0.91; p for trend = 0.012) for omega-3 fatty acids; and 0.56 (0.38-0.83; p for trend = 0.01) for (MUFA+PUFA):saturated fatty acid ratio after adjustment for age, sex, number of years of education, and caloric intake. In this study, higher intake of PUFA and MUFA was associated with a reduced likelihood of MCI among elderly persons in the population-based setting.

OBJECTIVE

We sought to develop risk scores for the progression from cognitively normal (CN) to mild cognitive impairment (MCI).

METHODS

We recruited into a longitudinal cohort study a randomly selected, population-based sample of Olmsted County, MN, residents, aged 70 to 89 years on October 1, 2004. At baseline and subsequent visits, participants were evaluated for demographic, clinical, and neuropsychological measures, and were classified as CN, MCI, or dementia. Using baseline demographic and clinical variables in proportional hazards models, we derived scores that predicted the risk of progressing from CN to MCI. We evaluated the ability of these risk scores to classify participants for MCI risk.

RESULTS

Of 1,449 CN participants, 401 (27.7%) developed MCI. A basic model had a C statistic of 0.60 (0.58 for women, 0.62 for men); an augmented model resulted in a C statistic of 0.70 (0.69 for women, 0.71 for men). Both men and women in the highest vs lowest sex-specific quartiles of the augmented model's risk scores had an approximately 7-fold higher risk of developing MCI. Adding APOE ε4 carrier status improved the model (p = 0.002).

CONCLUSIONS

We have developed MCI risk scores using variables easily assessable in the clinical setting and that may be useful in routine patient care. Because of variability among populations, validation in independent samples is required. These models may be useful in identifying patients who might benefit from more expensive or invasive diagnostic testing, and can inform clinical trial design. Inclusion of biomarkers or other risk factors may further enhance the models.

OBJECTIVE

To determine risk and protective factors for mild cognitive impairment (MCI) among persons 85 years and older.

METHODS

Participants in the population-based prospective Mayo Clinic Study of Aging were comprehensively evaluated at baseline and at 15 monthly intervals to determine incident MCI. At baseline, lifestyle factors in midlife and late life were assessed by self-reported questionnaire; vascular and comorbid conditions were abstracted from participants' medical records.

RESULTS

Of 256 participants who were cognitively normal at enrollment (median age 87.3 years, 62% women), 121 developed MCI at a median 4.1 years of follow-up. Predictors of MCI were APOE ε4 allele (hazard ratio [HR] 1.89; p = 0.008), current depressive symptoms (HR 1.78; p = 0.02), midlife onset of hypertension (HR 2.43; p = 0.005), increasing number of vascular diseases (HR 1.13; p = 0.02), and chronic conditions from the Charlson Comorbidity Index (HR 1.08; p = 0.006). Models were adjusted for sex and education, with age as the time variable. The risk of MCI was reduced for participants who reported engagement in artistic (HR 0.27; p = 0.03), craft (HR 0.55; p = 0.02), and social (HR 0.45; p = 0.005) activities in both midlife and late life, and in the use of a computer in late life (HR 0.47; p = 0.008).

CONCLUSIONS

Chronic disease burden increases risk of MCI, whereas certain lifestyle factors reduce risk in persons 85 years and older. This implies that preventive strategies for MCI may need to begin in midlife and should persist throughout late life.

OBJECTIVE

We determined whether head trauma was associated with amyloid deposition and neurodegeneration among individuals who were cognitively normal (CN) or had mild cognitive impairment (MCI).

METHODS

Participants included 448 CN individuals and 141 individuals with MCI from the Mayo Clinic Study of Aging who underwent Pittsburgh compound B (PiB)-PET, fluorodeoxyglucose-PET, and MRI. Head trauma was defined as a self-reported brain injury with at least momentary loss of consciousness or memory. Regression models examined whether head trauma was associated with each neuroimaging variable (assessed as continuous and dichotomous measures) in both CN and MCI participants, controlling for age and sex.

RESULTS

Among 448 CN individuals, 74 (17%) self-reported a head trauma. There was no difference in any neuroimaging measure between CN subjects with and without head trauma. Of 141 participants with MCI, 25 (18%) self-reported a head trauma. MCI participants with a head trauma had higher amyloid levels (by an average 0.36 standardized uptake value ratio units, p = 0.002).

CONCLUSIONS

Among individuals with MCI, but not CN individuals, self-reported head trauma with at least momentary loss of consciousness or memory was associated with greater amyloid deposition, suggesting that head trauma may be associated with Alzheimer disease-related neuropathology. Differences between CN individuals and individuals with MCI raise questions about the relevance of head injury-PET abnormality findings in those with MCI.

OBJECTIVE

To examine the association between computer use, physical exercise, aging, and mild cognitive impairment (MCI).

METHODS

The Mayo Clinic Study of Aging is a population-based study of aging and MCI in Olmsted County, Minnesota. The study sample consists of a random sample of 926 nondemented individuals aged 70 to 93 years who completed self-reported questionnaires on physical exercise, computer use, and caloric intake within 1 year of the date of interview. The study was conducted from April 1, 2006, through November 30, 2008. An expert consensus panel classified each study participant as cognitively normal or having MCI on the basis of published criteria.

RESULTS

Using a multivariable logistic regression model, we examined the impact of the presence during the study period of 2 lifestyle factors (physical exercise and computer use) after adjusting for a third lifestyle factor (caloric intake) on aging and MCI. We also adjusted for age, sex, education, medical comorbidity, and depression. The median daily caloric intake was significantly higher in participants with MCI than in controls (odds ratio, 1.04; 95% confidence interval, 1.02-1.06; P=.001). Participants who engaged in both moderate physical exercise and computer use had significantly decreased odds of having MCI (odds ratio [95% confidence interval], 0.36 [0.20-0.68]) compared with the reference group. In the interaction analyses, there was an additive interaction (P=.012) but not multiplicative interaction (P=.780).

CONCLUSIONS

In this population-based sample, the presence of both physical exercise and computer use as assessed via survey was associated with decreased odds of having MCI, after adjustment for caloric intake and traditional confounders.

OBJECTIVE

An association of clinical and subclinical hypothyroidism with mild cognitive impairment (MCI) has not been established.

OBJECTIVE

To evaluate the association of clinical and subclinical hypothyroidism with MCI in a large population-based cohort.

METHODS

A cross-sectional, population-based study was conducted in Olmsted County, Minnesota. Randomly selected participants were aged 70 to 89 years on October 1, 2004, and were without documented prevalent dementia [CORRECTED]. A total of 2050 participants were evaluated and underwent in-person interview, neurologic evaluation, and neuropsychological testing to assess performance in memory, attention/executive function, and visuospatial and language domains. Participants were categorized by consensus as being cognitively normal, having MCI, or having dementia according to published criteria. Clinical and subclinical hypothyroidism were ascertained from a medical records linkage system.

METHODS

Association of clinical and subclinical hypothyroidism with MCI.

RESULTS

Among 1904 eligible participants, the frequency of MCI was 16% in 1450 individuals with normal thyroid function, 17% in 313 persons with clinical hypothyroidism, and 18% in 141 individuals with subclinical hypothyroidism. After adjusting for covariates (age, educational level, sex, apolipoprotein E ε4, depression, diabetes mellitus, hypertension, stroke, body mass index, and coronary artery disease) we found no significant association between clinical or subclinical hypothyroidism and MCI (odds ratio [OR], 0.99 [95% CI, 0.66-1.48] and 0.88 [0.38-2.03], respectively). No effect of sex interaction was seen on these effects. In stratified analysis, the odds of MCI with clinical and subclinical hypothyroidism among men was 1.02 (95% CI, 0.57-1.82) and 1.29 (0.68-2.44) and, among women, was 1.04 (0.66-1.66) and 0.86 (0.37-2.02), respectively.

CONCLUSIONS

In this population-based cohort of elderly people, neither clinical nor subclinical hypothyroidism was associated with MCI. Our findings need to be validated in a separate setting using the published criteria for MCI and confirmed in a longitudinal study.

One of the key research agenda of the field of aging is investigation of presymptomatic Alzheimer's disease (AD). Furthermore, abnormalities in brain glucose metabolism (as measured by FDG-PET) have been reported among cognitively normal elderly persons. However, little is known about the association of FDG-PET abnormalities with neuropsychiatric symptoms (NPS) in a population-based setting. Thus, we conducted a cross-sectional study derived from the ongoing population-based Mayo Clinic Study of Aging in order to examine the association between brain glucose metabolism and NPS among cognitively normal (CN) persons aged>> 70 years. Participants underwent FDG-PET and completed the Neuropsychiatric Inventory Questionnaire (NPI-Q), Beck Depression Inventory (BDI), and Beck Anxiety Inventory (BAI). Cognitive classification was made by an expert consensus panel. We conducted multivariable logistic regression analyses to compute odds ratios (OR) and 95% confidence intervals after adjusting for age, sex, and education. For continuous variables, we used linear regression and Spearman rank-order correlations. Of 668 CN participants (median 78.1 years, 55.4% males), 205 had an abnormal FDG-PET (i.e., standardized uptake value ratio < 1.32 in AD-related regions). Abnormal FDG-PET was associated with depression as measured by NPI-Q (OR = 2.12; 1.23-3.64); the point estimate was further elevated for APOE ɛ4 carriers (OR = 2.59; 1.00-6.69), though marginally significant. Additionally, we observed a significant association between abnormal FDG-PET and depressive and anxiety symptoms when treated as continuous measures. These findings indicate that NPS, even in community-based samples, can be an important additional tool to the biomarker-based investigation of presymptomatic AD.

Although rates of incident dementia have been reported from several populations, the impact of nonparticipation on dementia incidence in studies of cognitive aging is unknown. In 2004, investigators with the Mayo Clinic Study of Aging selected persons aged 70-89 years from an enumeration of all Olmsted County, Minnesota, residents (age- and sex-stratified random sample). Of 4,398 potential participants, 2,050 agreed to undergo an in-person health assessment. Those participants were reevaluated in person using standard diagnostic procedures approximately every 15 months over a median follow-up period of 5.7 years (through September 15, 2013). There were 1,679 persons who refused any participation. A trained nurse abstractor reviewed the medical records of nonparticipants using the Rochester Epidemiology Project's medical record linkage system a median of 3.9 years after refusal. Nonparticipants had a higher prevalence of dementia than participants evaluated in person (6.5% vs. 3.3%; P < 0.0001). The standardized incidence of dementia was not significantly higher among the nonparticipants (23.2 per 1,000 person-years) than in those evaluated in person (19.6 per 1,000 person-years; hazard ratio = 1.17, 95% confidence interval: 0.95, 1.43 (P = 0.13); adjusted for education and sex, with age as the time scale). The small, nonsignificant impact of nonparticipation on rates of incident dementia is reassuring for future studies based on incident dementia cases.

OBJECTIVE

It remains unknown whether the association between diabetes mellitus (DM) and cognitive function differs in Eastern and Western populations. This study aimed to elucidate whether DM is associated with worse cognitive performance in both populations.

METHODS

The Shanghai Aging Study (SAS) and the Mayo Clinic Study of Aging (MCSA) are two population-based studies with similar design and methodology in Shanghai, China and Rochester, MN, USA. Non-demented participants underwent cognitive testing, and DM was assessed from the medical record. Separate analyses were performed in SAS and MCSA regarding the association between DM and cognitive performance.

RESULTS

A total of 3,348 Chinese participants in the SAS and 3,734 American subjects in the MCSA were included. Compared with MCSA subjects, SAS participants were younger, less educated, and had lower frequency of vascular disease, APOE ɛ4 carriers and obesity. Participants with DM (compared to non-DM participants) performed significantly worse on all the cognitive domains in both the SAS and MCSA. After adjustment for age, gender, education, and vascular covariates, DM was associated with worse performance in executive function (β=-0.15, p = 0.001 for SAS, and β=-0.10, p = 0.008 for MCSA) in the total sample and in the cognitively normal sub-sample. Furthermore, DM was associated with poor performance in visuospatial skills, language, and memory in the SAS, but not in the MCSA.

CONCLUSIONS

Diabetes is associated with cognitive dysfunction and, in particular, exerts a negative impact on executive function regardless of race, age, and prevalence of vascular risk factors.

Cross-sectional associations between engagement in mentally stimulating activities and decreased odds of having mild cognitive impairment (MCI) or Alzheimer disease have been reported. However, little is known about the longitudinal outcome of incident MCI as predicted by late-life (aged ≥70 years) mentally stimulating activities.

To test the hypothesis of an association between mentally stimulating activities in late life and the risk of incident MCI and to evaluate the influence of the apolipoprotein E (APOE) ε4 genotype.

This investigation was a prospective, population-based cohort study of participants in the Mayo Clinic Study of Aging in Olmsted County, Minnesota. Participants 70 years or older who were cognitively normal at baseline were followed up to the outcome of incident MCI. The study dates were April 2006 to June 2016.

At baseline, participants provided information about mentally stimulating activities within 1 year before enrollment into the study. Neurocognitive assessment was conducted at baseline, with evaluations at 15-month intervals. Cognitive diagnosis was made by an expert consensus panel based on published criteria. Hazard ratios (HRs) and 95% CIs were calculated using Cox proportional hazards regression models after adjusting for sex, age, and educational level.

The final cohort consisted of 1929 cognitively normal persons (median age at baseline, 77 years [interquartile range, 74-82 years]; 50.4% [n = 973] female) who were followed up to the outcome of incident MCI. During a median follow-up period of 4.0 years, it was observed that playing games (HR, 0.78; 95% CI, 0.65-0.95) and engaging in craft activities (HR, 0.72; 95% CI, 0.57-0.90), computer use (HR, 0.70; 95% CI, 0.57-0.85), and social activities (HR, 0.77; 95% CI, 0.63-0.94) were associated with a decreased risk of incident MCI. In a stratified analysis by APOE ε4 carrier status, the data point toward the lowest risk of incident MCI for APOE ɛ4 noncarriers who engage in mentally stimulating activities (eg, computer use: HR, 0.73; 95% CI, 0.58-0.92) and toward the highest risk of incident MCI for APOE ɛ4 carriers who do not engage in mentally stimulating activities (eg, no computer use: HR, 1.74; 95% CI, 1.33-2.27).

Cognitively normal elderly individuals who engage in specific mentally stimulating activities even in late life have a decreased risk of incident MCI. The associations may vary by APOE ε4 carrier status.

The authors conducted a cross-sectional study to investigate the association between anxiety symptoms and cortical thickness, as well as amygdalar volume. A total of 1,505 cognitively normal participants, aged ≥70 years, were recruited from the Mayo Clinic Study of Aging in Olmsted County, Minnesota, on whom Beck Anxiety Inventory and 3T brain MRI data were available. Even though the effect sizes were small in this community-dwelling group of participants, anxiety symptoms were associated with reduced global cortical thickness and reduced thickness within the frontal and temporal cortex. However, after additionally adjusting for comorbid depressive symptoms, only the association between anxiety symptoms and reduced insular thickness remained significant.