Objective: To understand the neuropsychological basis of dementia risk among persons in the spectrum including cognitive normality and mild cognitive impairment. Methods: We quantitated risk of progression to dementia in elderly persons without dementia from 2 population-based studies, the Framingham Heart Study (FHS) and Mayo Clinic Study of Aging (MCSA), aged 70 to 89 years at enrollment. Baseline cognitive status was defined by performance in 4 domains derived from batteries of neuropsychological tests (that were similar but not identical for FHS and MCSA) at cut scores corresponding to SDs of ≤−0.5, −1, −1.5, and −2 from normative means. Participants were characterized as having no cognitive impairment (reference group), or single or multiple amnestic or nonamnestic profiles at each cut score. Incident dementia over the following 6 years was determined by consensus committee at each study separately. Results: The pattern of hazard ratios for incident dementia, rates of incident dementia and positive predictive values across cognitive test cut scores, and number of affected domains was similar although not identical across the FHS and MCSA. Dementia risks were higher for amnestic profiles than for nonamnestic profiles, and for multidomain compared with single-domain profiles. Conclusions: Cognitive domain subtypes, defined by neuropsychologically derived cut scores and number of low-performing domains, differ substantially in prognosis in a conceptually logical manner that was consistent between FHS and MCSA. Neuropsychological characterization of elderly persons without dementia provides valuable information about prognosis. The heterogeneity of risk of dementia cannot be captured concisely with one test or a single definition or cutpoint.

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.

We conducted a preliminary case control investigation of the association of pancreatic polypeptide (PP) with mild cognitive impairment (MCI) in 202 MCI cases (mean age, 81.6 years) and 202 age- and sex-matched cognitively normal controls in the Mayo Clinic Study of Aging. Plasma PP was measured and examined as the natural logarithm (continuous) and dichotomized at the median. The OR (95% Cl) of MCI increased with increasing PP [1.46 (1.04-2.05)]. There was a negative interaction of PP with apolipoprotein E (APOE) c4 allele; compared to the reference group (no APOE c4 allele and low PP), the OR (95% Cl) for combinations of c4 and PP were: 2.64 (1.39-5.04) for APOE E4 plus low PP; 2.09 (1.27-3.45) for no APOE E4 plus high PP; and 1.91 (1.04-3.53) for no APOE c4 plus high PP (P for interaction = 0.017). There was also a trend toward a negative interaction with type 2 diabetes (P for interaction = 0.058). Compared to no diabetes and low PP, the OR (95% Cl) was 3.02 (1.22-7.46) for low PP plus diabetes but 1.80 (1.01-3.22) for high PP plus diabetes. Participants with high PP had a greater mean (SD) weight loss (kilograms per decade) than persons with low PP [-2.27 (4.07) vs. 1.61(5.24); P = 0.016]. MCI cases had a non-significantly greater weight loss per decade compared to controls. These findings suggest that high PP alone or jointly with APOE c4 allele or type 2 diabetes is associated with MCI, and that high PP may mitigate some effects of APOE c4 allele and type 2 diabetes on cognition. Potential mechanisms may involve PP-related weight loss and centrally mediated effects of PP on cognition. These findings remain to be validated in other studies.

Background and Objectives: 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 epsilon 4 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 (beta = -0.15, p = 0.001 for SAS, and beta = -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.

The objective of this study was to investigate the cross-sectional associations of atrial fibrillation with neuroimaging measures of cerebrovascular disease and Alzheimer’s disease-related pathology, and their interaction with cognitive impairment. MRI scans of non-demented individuals (n=1044) from the population-based Mayo Clinic Study of Aging were analyzed for infarctions, total grey matter, hippocampal and white matter hyperintensity volumes. A subset of 496 individuals underwent FDG and C-11 Pittsburgh compound B (PiB) PET scans. We assessed the associations of atrial fibrillation with i) categorical MRI measures (cortical and subcortical infarctions) using multivariable logistic regression models, and with ii) continuous MRI measures ( hippocampal, total grey matter, and white matter hyperintensity volumes) and FDG-PET and PiB-PET measures using multivariable linear regression models, and adjusting for confounders. Among participants who underwent MRI (median age, 77.8, 51.6% male), 13.5% had atrial fibrillation. Presence of atrial fibrillation was associated with subcortical infarctions (odds ratio [OR], 1.83; p=0.002), cortical infarctions (OR, 1.91; p=0.03), total grey matter volume (Beta [β], -.025, p<.0001) after controlling for age, education, gender, APOE e4 carrier status, coronary artery disease, diabetes, history of clinical stroke, and hypertension. However, atrial fibrillation was not associated with white matter hyperintensity volume, hippocampal volume, Alzheimer’s pattern of FDG hypometabolism or PiB uptake. There was a significant interaction of cortical infarction (p for interaction=0.004) and subcortical infarction (p for interaction =0.015) with atrial fibrillation with regards to odds of mild cognitive impairment (MCI). Using subjects with no atrial fibrillation and no infarction as the reference, the OR (95% confidence intervals [CI]) for MCI was 2.98 (1.66, 5.35;p = 0.0002) among participants with atrial fibrillation and any infarction, 0.69 (0.36, 1.33;p= 0.27) for atrial fibrillation and no infarction, and 1.50 (0.96, 2.32;p = 0.07) for no atrial fibrillation and any infarction. These data highlight that atrial fibrillation is associated with MCI in the presence of infarctions.

OBJECTIVE: To determine the association between multimorbidity and risk of mild cognitive impairment (MCI) and dementia. BACKGROUND: Multimorbidity, the coexistence of 2 or more chronic conditions in an individual, is highly prevalent among older adults. Multimorbidity may contribute to increased risk of MCI, an important precursor for Alzheimer's disease and other dementias. However, the association has not been comprehensively investigated in a population-based setting. DESIGN/METHODS: Prospective study involving cognitively normal subjects enrolled in the Mayo Clinic Study of Aging (MCSA) in Olmsted County, Minnesota. Participants underwent a clinical evaluation at baseline and 15-month intervals to determine diagnoses of MCI and dementia. Information on International Classification of Diseases, ninth revision (ICD-9) codes for chronic conditions in the five years prior to enrollment was electronically captured using the Rochester Epidemiology Project medical records linkage system. Multimorbidity was defined as having two or more chronic conditions. The association of multimorbidity with MCI/dementia was examined using Cox proportional hazards models. RESULTS: Among 2,174 cognitively normal participants (mean [SD] age 78.5 [5.2] years; 50.6[percnt] men), 1,684 (77.5[percnt]) had multimorbidity. The risk of MCI/dementia was elevated in persons with multimorbidity (hazard ratio [HR]: 1.47; 95[percnt] Confidence interval [CI], 1.14-1.89). In addition, there was a significant dose response association with increasing number of chronic conditions (p for trend = 0.002). CONCLUSIONS: In older adults, having multiple chronic conditions is associated with an increased risk of MCI/dementia, and is consistent with the hypothesis that multiple etiologies may contribute to MCI and late-life dementia. Preventing chronic diseases may be useful in delaying or preventing MCI or dementia Study Supported by: National Institutes of Health grants U01 AG006786, K01 AG028573, P50 AG016574, K01 MH068351; by the Robert H. and Clarice Smith and Abigail van Buren Alzheimer's Disease Research Program and was made possible by the Rochester Epidemiology Project (R01AG034676).

OBJECTIVES: To determine the association between multiple chronic conditions and risk of incident mild cognitive impairment (MCI) and dementia.DESIGN: Prospective cohort study.SETTING: Olmsted County, Minnesota.PARTICIPANTS: Cognitively normal individuals (N = 2,176) enrolled in the Mayo Clinic Study of Aging (MCSA).MEASUREMENTS: Participants were randomly selected from the community, evaluated by a physician, and underwent neuropsychometric testing at baseline and at 15-month intervals to assess diagnoses of MCI and dementia. Information on International Classification of Diseases, Ninth Revision codes for chronic conditions in the 5 years before enrollment was electronically captured using the Rochester Epidemiology Project medical records linkage system. Multimorbidity was defined as having two or more chronic conditions, and the association between multimorbidity and MCI and dementia was examined using Cox proportional hazards models.RESULTS: Of 2,176 cognitively normal participants (mean age +/- standard deviation 78.5 +/- 5.2; 50.6% male), 1,884 (86.6%) had multimorbidity. The risk of MCI or dementia was higher in persons with multimorbidity (hazard ratio (HR) = 1.38, 95% confidence interval (CI) = 1.05-1.82) than in those with one or no chronic condition. The HR was of greater magnitude in persons with four or more conditions (HR = 1.61, 95% CI = 1.21-2.13) than in those with two or three conditions (HR = 1.03, 95% CI = 0.76-1.39) and for men with multimorbidity(HR = 1.53, 95% CI = 1.01-2.31) than for women with multimorbidity (HR = 1.20, 95% CI = 0.83-1.74), compared to those with one or no chronic condition.CONCLUSION: In older adults, having multiple chronic conditions is associated with greater risk of MCI and dementia. This is consistent with the hypothesis that multiple etiologies may contribute to MCI and late-life dementia. Preventing chronic diseases may be beneficial in delaying or preventing MCI and dementia.

Introduction: The objective of our study was to investigate cross-sectional associations of atrial fibrillation with neuroimaging measures of cerebrovascular disease and Alzheimer's disease and their interactions with mild cognitive impairment (MCI).Methods: Magnetic resonance imaging scans of individuals from a population-based study were analyzed for infarctions, total gray matter, and hippocampal and white matter hyperintensity volumes. A subsample underwent positron emission tomography imaging.Results: Atrial fibrillation was associated with infarctions and lower total gray matter volume. Compared with subjects with no atrial fibrillation and no infarction, the odds ratio (95% confidence intervals) for MCI was 2.99 (1.57-5.70; P = .001) among participants with atrial fibrillation and infarction, 0.90 (0.45-1.80; P = .77) for atrial fibrillation and no infarction, and 1.50 (0.96-2.34; P = .08) for no atrial fibrillation and any infarction.Discussion: Participants with both atrial fibrillation and infarction are more likely to have MCI than participants with either infarction or atrial fibrillation alone. (C) 2016 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

BACKGROUND:Etiologic differences in mild cognitive impairment (MCI) subtypes may impact mortality.OBJECTIVE:To assess the rate of death in MCI overall, and by subtype, in the population-based Mayo Clinic Study of Aging.METHODS:Participants aged 70-89 years at enrollment were clinically evaluated at baseline and 15-month intervals to assess diagnoses of MCI and dementia. Mortality in MCI cases versus cognitively normal (CN) individuals was estimated using Cox proportional hazards models.RESULTS:Over a median follow-up of 5.8 years, 331 of 862 (38.4%) MCI cases and 224 of 1,292 (17.3%) cognitively normal participants died. Compared to CN individuals, mortality was elevated in persons with MCI (hazard ratio [HR] = 1.79; 95% CI: 1.41 to 2.27), and was higher for non-amnestic MCI (naMCI; HR = 2.40; 95% CI: 1.72 to 3.36) than for amnestic MCI (aMCI; HR = 1.61; 95% CI: 1.25 to 2.09) after adjusting for confounders. Mortality varied significantly by sex, education, history of heart disease, and engaging in moderate physical exercise (p for interaction <0.05 for all). Mortality rate estimates were highest in MCI cases who were men, did not exercise, had heart disease, and had higher education versus CN without these factors, and for naMCI cases versus aMCI cases without these factors.CONCLUSIONS:These findings suggest stronger impact of etiologic factors on naMCI mortality. Prevention of heart disease, exercise vigilance, may reduce MCI mortality and delayed MCI diagnosis in persons with higher education impacts mortality.

Dysfunctional insulin signaling may affect brain metabolism or amyloid deposition. We investigated the associations of type 2 diabetes with amyloid accumulation measured using 11C-Pittsburgh compound B (11C-PiB) and brain hypometabolism measured using 18F-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 18F-FDG PET. Alzheimer disease (AD) signature and region-of-interest (ROI) measures for 11C-PiB retention ratio and 18F-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), 18F-FDG hypometabolism (18F-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 18F-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 18F-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 11C-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). Conclusion: 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.

Importance Previous studies suggest cross-sectional associations between a diagnosis of chronic obstructive pulmonary disease (COPD) and mild cognitive impairment (MCI). However, few studies have assessed whether COPD, a potentially modifiable factor, is associated with an increased risk for MCI and whether the relation is specific to the type of MCI. Objective To investigate whether a diagnosis of COPD and duration of COPD are associated with an increased risk for incident MCI and MCI subtypes (amnestic MCI [A-MCI] and nonamnestic MCI [NA-MCI]). Design, Setting, and Participants A prospective population-based cohort from the Mayo Clinic Study on Aging. We included 1425 cognitively normal individuals aged 70 to 89 years who were randomly selected from Olmsted County, Minnesota, on October 1, 2004, using the medical records linkage system. At baseline and every 15 months thereafter, participants underwent assessment with a nurse interview, neurologic examination, and neuropsychological testing. A diagnosis of COPD was confirmed via medical record review. A baseline diagnosis of COPD and duration of COPD were examined as risk factors for MCI and MCI subtypes using Cox proportional hazards models and adjusting for demographic variables and medical comorbidities, with age as the time scale. Exposure A baseline diagnosis of COPD and duration of COPD. Main Outcomes and Measures Incident MCI, A-MCI, and NA-MCI. Results Of the 1425 participants with normal cognition at baseline, 370 developed incident MCI. The median duration of follow-up was 5.1 years (interquartile range, 3.8-5.4 years). A diagnosis of COPD significantly increased the risk for NA-MCI by 83% (hazard ratio, 1.83 [95% CI, 1.04-3.23]), but not of any MCI or A-MCI in multivariate analyses. We found a dose-response relationship such that individuals with COPD duration of longer than 5 years at baseline had the greatest risk for any MCI (hazard ratio, 1.58 [95% CI, 1.04-2.40]) and NA-MCI (2.58 [1.32-5.06]). Conclusions and Relevance A diagnosis of COPD is associated with an increased risk for MCI, particularly NA-MCI. We have found a dose-response relationship between COPD duration and risk for MCI. These findings highlight the importance of COPD as a risk factor for MCI and may provide a substrate for early intervention to prevent or delay the onset and progression of MCI, particularly NA-MCI.

Efforts to reduce the burden of cognitive impairment have shifted toward younger persons, with good reason. However, a large number of individuals at older ages remain at increased risk, and it is equally urgent to determine factors that may prevent mild cognitive impairment (MCI) or dementia among very old persons. We investigated the predictors of cognitive impairment among very old persons from a prospective study. Participants were aged 85 and older at enrollment to the population-based, prospective, Mayo Clinic Study of Aging. They underwent a comprehensive evaluation at baseline and at 15 monthly intervals to determine incident MCI or dementia. Demographic, psychiatric, and life style factors were measured at baseline by self-report and vascular risk factors were abstracted from the medical records using a medical records linkage system. Among 256 subjects (median age 87 years, 62% women) who were cognitively normal at enrollment 121 progressed to incident MCI (27 MCI cases further progressed to dementia) over a median 4.1 years of follow-up. Predictors of MCI or dementia included APOE e 4 allele, (hazard ratio [HR], 1.89; p = 0.008), current depressive symptoms (1.78, p = 0.02), and onset of hypertension in midlife (HR, 2.56, p = 0.003; HR for late-life onset of hypertension was non-significantly elevated, HR, 1.70; p = 0.07). Protective factors for MCI or dementia were involvement in artistic or craft activities (e.g. painting, sculpting, woodworking, knitting, quilting; HR, 0.57, p = 0.008); and use of a computer in late-life (HR, 0.60, p = 0.03) in models adjusted for sex and education, using age as a time variable. In a multivariable model simultaneously including all the variables, having an APOE e 4 allele remained a risk factor and involvement in artistic or craft activities and use of a computer remained statistically significant protective factors. Our findings suggest that lifestyle factors that may preserve cognition in very old persons. They also underscore the importance of hypertension prevention in mid-life as a key preventive strategy for late-life cognitive impairment.

Peripheral blood telomere length has been associated with age-related conditions including Alzheimer's disease (AD). This suggests that telomere length may identify subjects at increased risk of AD. Thus, we investigated the associations of peripheral blood telomere length with amnestic mild cognitive impairment (aMCI), a putative precursor of AD, among Mayo Clinic Study of Aging participants who were prospectively followed for incident aMCI. We matched 137 incident aMCI cases (mean age 81.1 years, [range 70.9-90.8]; 49.6% men) by age and sex to 137 cognitively normal controls. We measured telomere length (T/S ratio) at baseline using quantitative PCR. Compared to the middle T/S quintile (Q3), the risk of aMCI was elevated for subjects with the shortest (Q1: HR, 2.85, 95% Confidence interval [CI] 0.98, 8.25; p=0.05) and the longest telomere lengths (Q5: HR, 5.58, 95%CI, 2.21, 14.11; p=0.0003). In this elderly cohort, short and long telomeres were associated with increased risk of aMCI. Our findings suggest that both long and short telomere lengths may play a role in the pathogenesis of aMCI, and may be markers of increased risk of aMCI.

Objective:To estimate rates of progression from mild cognitive impairment (MCI) to dementia and of reversion from MCI to being cognitively normal (CN) in a population-based cohort.Methods:Participants (n = 534, aged 70 years and older) enrolled in the prospective Mayo Clinic Study of Aging were evaluated at baseline and every 15 months to identify incident MCI or dementia.Results:Over a median follow-up of 5.1 years, 153 of 534 participants (28.7%) with prevalent or incident MCI progressed to dementia (71.3 per 1,000 person-years). The cumulative incidence of dementia was 5.4% at 1 year, 16.1% at 2, 23.4% at 3, 31.1% at 4, and 42.5% at 5 years. The risk of dementia was elevated in MCI cases (hazard ratio [HR] 23.2, p < 0.001) compared with CN subjects. Thirty-eight percent (n = 201) of MCI participants reverted to CN (175.0/1,000 person-years), but 65% subsequently developed MCI or dementia; the HR was 6.6 (p < 0.001) compared with CN subjects. The risk of reversion was reduced in subjects with an APOE epsilon 4 allele (HR 0.53, p < 0.001), higher Clinical Dementia Rating Scale-Sum of Boxes (HR 0.56, p < 0.001), and poorer cognitive function (HR 0.56, p < 0.001). The risk was also reduced in subjects with amnestic MCI (HR 0.70, p = 0.02) and multidomain MCI (HR 0.61, p = 0.003).Conclusions:MCI cases, including those who revert to CN, have a high risk of progressing to dementia. This suggests that diagnosis of MCI at any time has prognostic value.

Background: Type 2 diabetes may increase the risk of amnestic mild cognitive impairment (aMCI) through Alzheimer's disease (AD)-related and vascular pathology and may also increase the risk of non-amnestic MCI (naMCI) through vascular disease mechanisms. We examined the association of type 2 diabetes with mild cognitive impairment (MCI) and MCI subtype (aMCI and naMCI) overall and by sex.Methods: Participants were Olmsted County, Minnesota residents (70 years and older) enrolled in a prospective, population-based study. At baseline and every 15 months thereafter, participants were evaluated using the Clinical Dementia Rating scale, a neurological evaluation, and neuropsychological testing for a diagnosis of normal cognition, MCI, and dementia by a consensus panel. Type 2 diabetes was ascertained from the medical records of participants at baseline.Results: Over a median 4.0 years of follow-up, 348 of 1450 subjects developed MCI. Type 2 diabetes was associated (hazard ratio [95% confidence interval]) with MCI (1.39 [1.08-1.79]), aMCI (1.58 [1.17-2.15]; multiple domain: 1.58 [1.01-2.47]; single domain: 1.49 [1.09-2.05]), and the hazard ratio for naMCI was elevated (1.37 [0.84-2.24]). Diabetes was strongly associated with multiple-domain aMCI in men (2.42 [1.31-4.48]) and an elevated risk of multiple domain naMCI in men (2.11 [0.70-6.33]), and with single domain naMCI in women (2.32 [1.04-5.20]).Conclusions: Diabetes was associated with an increased risk of MCI in elderly persons. The association of diabetes with MCI may vary with subtype, number of domains, and sex. Prevention and control of diabetes may reduce the risk of MCI and Alzheimer's disease. (C) 2014 The Alzheimer's Association. All rights reserved.

OBJECTIVE: To investigate cross-sectional associations of diabetes with amyloid accumulation measured using 11C-Pittsburgh Compound B (PIB) and with brain hypometabolism measured using 18F-fluorodeoxyglucose (FDG) positron emission tomography.

OBJECTIVE To investigate the association of cardiac disease with amnestic and nonamnestic mild cognitive impairment (aMCI and naMCI, respectively). Nonamnestic mild cognitive impairment, a putative precursor of vascular and other non-Alzheimer dementias, is hypothesized to have a vascular etiology. DESIGN A prospective, population-based, cohort study with a median 4.0 years of follow-up. SETTING Olmsted County, Minnesota. PARTICIPANTS A total of 2719 participants were evaluated at baseline and every 15 months using the Clinical Dementia Rating scale, a neurological evaluation, and neuropsychological testing. A diagnosis of normal cognition, MCI, or dementia was made by consensus. Cardiac disease at baseline was assessed from the participant's medical records. MAIN OUTCOME MEASURES Incident MCI, aMCI, or naMCI. RESULTS Of 1450 participants without MCI or dementia at baseline, 366 developed MCI. Cardiac disease was associated with an increased risk of naMCI (hazard ratio, 1.77 [95% CI, 1.16-2.72]). However, the association varied by sex (P = .02 for interaction). Cardiac disease was associated with an increased risk of naMCI (hazard ratio, 3.07 [95% CI, 1.58-5.99]) for women but not for men (hazard ratio, 1.16 [95% CI, 0.68-1.99]). Cardiac disease was not associated with any type of MCI or with aMCI. CONCLUSIONS Cardiac disease is an independent risk factor for naMCI; within-sex comparisons showed a stronger association for women. Prevention and management of cardiac disease and vascular risk factors may reduce the risk of naMCI.