Atrial fibrillation, cognitive impairment, and neuroimaging.

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.

Association of Pancreatic Polypeptide with Mild Cognitive Impairment Varies by APOE ε4 Allele.

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% CI) of MCI increased with increasing PP [1.46 (1.04-2.05)]. There was a negative interaction of PP with apolipoprotein E (APOE) ε4 allele; compared to the reference group (no APOE ε4 allele and low PP), the OR (95% CI) for combinations of ε4 and PP were: 2.64 (1.39-5.04) for APOE ε4 plus low PP; 2.09 (1.27-3.45) for no APOE ε4 plus high PP; and 1.91 (1.04-3.53) for no APOE ε4 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% CI) 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 ε4 allele or type 2 diabetes is associated with MCI, and that high PP may mitigate some effects of APOE ε4 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.

Spectrum of cognition short of dementia: Framingham Heart Study and Mayo Clinic Study of Aging.

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.

Multimorbidity and Risk of Mild Cognitive Impairment.

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.

Risk and protective factors for cognitive impairment in persons aged 85 years and older.

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.

Mortality in mild cognitive impairment varies by subtype, sex, and lifestyle factors: the Mayo Clinic Study of Aging.

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.

Short and long telomeres increase risk of amnestic mild 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.

Incidence of dementia among participants and nonparticipants in a longitudinal study of cognitive aging.

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.

Diabetes and elevated hemoglobin A1c levels are associated with brain hypometabolism but not amyloid accumulation.

UNLABELLED: 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). 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.

A prospective study of chronic obstructive pulmonary disease and the risk for mild cognitive impairment.

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.

Association of diabetes with amnestic and nonamnestic mild cognitive impairment.

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 nonamnestic 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.

Higher risk of progression to dementia in mild cognitive impairment cases who revert to normal.

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 ε4 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.

Cardiac disease associated with increased risk of nonamnestic cognitive impairment: stronger effect on women.

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.

ApoE and quality of life in nonagenarians.

OBJECTIVES: ApoE ε4 is associated with adverse health conditions that negatively impact the quality of life (QOL). The relationship between ApoE ε4 and QOL has not been explored in the oldest old. Our study aimed to examine ApoE in the oldest old and explore its association with QOL. DESIGN: Cross-sectional cohort study. SETTING: A medium sized community in Olmsted County, Minnesota. PARTICIPANTS: Individuals aged 90 to 99 years, living independently or in long term care environments. MEASUREMENTS: We collected demographic information and measured cognitive function (Short Test of Mental Status, Mini-Mental State Examination, Mattis Dementia Rating Scale), QOL (Linear Analogue Self Assessment), and ApoE distribution. Subjects were classified as cognitively normal, mild cognitive impairment, dementia, or dementia with stroke and/or parkinsonism (DEMSP). Regression model was used to assess the predictors of QOL. RESULTS: A total of 121 subjects (45 cognitively normal, 13 with mild cognitive impairment, 34 with dementia, 29 DEMSP) aged 90-99 years, 106 (87.6 %) females, were included. Frequency of ApoE ε3 allele was highest (194 [80.2%]: ε2/3 18, ε3/3 77, ε3/4 22) followed by ApoE ε4 (25 [10.3%]: ε2/4 3, ε3/4 22) and ApoE ε2 (23 [9.5%; ε2/2 1, ε2/3 18, ε2/4 3). None of the subjects carried ApoE ε4/4 genotype. QOL was similar between ApoE ε4 carrier and noncarriers. Physical well-being, emotional well-being, intellectual well-being, social connectedness, and coping ability were positively associated with QOL, whereas male sex, DEMSP, pain frequency, and pain severity were negatively associated. CONCLUSIONS: The most common ApoE in the oldest old was ε3/3 genotype and ε3 allele. No association was found between ApoE ε4 and QOL. However, those with high physical, emotional and intellectual well being, social connectedness, and coping ability had the highest overall QOL.

Relative intake of macronutrients impacts risk of mild cognitive impairment or dementia.

High caloric intake has been associated with an increased risk of cognitive impairment. Total caloric intake is determined by the calories derived from macronutrients. The objective of the study was to investigate the association between percent of daily energy (calories) from macronutrients and incident mild cognitive impairment (MCI) or dementia. Participants were a population-based prospective cohort of elderly persons who were followed over a median 3.7 years (interquartile range, 2.5-3.9) of follow-up. At baseline and every 15 months, participants (median age, 79.5 years) were evaluated using the Clinical Dementia Rating scale, a neurological evaluation, and neuropsychological testing for a diagnosis of MCI, normal cognition, or dementia. Participants also completed a 128-item food-frequency questionnaire at baseline; total daily caloric and macronutrient intakes were calculated using an established database. The percent of total daily energy from protein (% protein), carbohydrate (% carbohydrate), and total fat (% fat) was computed. Among 937 subjects who were cognitively normal at baseline, 200 developed incident MCI or dementia. The risk of MCI or dementia (hazard ratio, [95% confidence interval]) was elevated in subjects with high % carbohydrate (upper quartile: 1.89 [1.17-3.06]; p for trend = 0.004), but was reduced in subjects with high % fat (upper quartile: 0.56 [0.34-0.91]; p for trend = 0.03), and high % protein (upper quartile 0.79 [0.52-1.20]; p for trend = 0.03) in the fully adjusted models. A dietary pattern with relatively high caloric intake from carbohydrates and low caloric intake from fat and proteins may increase the risk of MCI or dementia in elderly persons.

What is the quality of life in the oldest old?

BACKGROUND: Maintaining and improving quality of life has become a major focus in geriatric medicine, but the oldest old have received limited attention in clinical investigations. We aimed to investigate the relationship between self-perceived and caregiver-perceived quality of life (QOL), cognitive functioning, and depressive symptoms in the oldest old. METHODS: This IRB-approved prospective study recruited community dwellers aged 90-99 years old. Collected data included neurological evaluation, DSM III-R criteria for dementia, Mini-Mental State Examination (MMSE), Dementia Rating Scale (DRS), Geriatric Depression Scale (GDS), Record of Independent Living (ROIL), and QOL assessment using the Linear Analogue Self Assessment (LASA). RESULTS: Data on 144 subjects (56 cognitively normal (normal), 13 mild cognitive impairment (MCI), 41 dementia (DEM), 34 dementia with stroke and parkinsonism (DEMSP)) over a three-year period were analyzed. Mean ages ranged from 93 to 94 years, and the majority were female with at least high school education. Overall functional ability was higher in groups without dementia (p < 0.0001). All subjects reported high overall QOL (range 6.76-8.3 out of 10), regardless of cognitive functioning. However, caregivers perceived the subjects' overall QOL to be lower with increasing severity of cognitive impairment (p < 0.0001). Lower GDS scores correlate with higher self-perceived overall QOL (ρ = -0.38, p < 0.0001). CONCLUSIONS: In our community sample of the oldest old, there was a fairly high level of overall QOL, whether or not cognitive impairment exists. Individuals perceive their QOL better than caregivers do, and the difference in subjects' and caregivers' perception is more pronounced for the groups with dementia. QOL is more strongly correlated with depressive symptoms than with dementia severity.

Polyunsaturated fatty acids and reduced odds of MCI: the Mayo Clinic Study of Aging.

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.

Vegetables, unsaturated fats, moderate alcohol intake, and mild cognitive impairment.

BACKGROUND/AIMS: 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]. CONCLUSION: Vegetables, unsaturated fats, and a high MeDi score may be beneficial to cognitive function.

Metabolic syndrome, inflammation, and nonamnestic mild cognitive impairment in older persons: a population-based study.

The metabolic syndrome (MetS) is more strongly associated with cognitive impairment in the presence of inflammation. This suggests that the association of MetS with mild cognitive impairment (MCI) may vary with the etiology and the subtype of MCI. This study investigated the association between MetS with or without inflammation and MCI [amnestic (a-MCI) and nonamnestic (na-MCI)]. We studied a randomly selected sample of 1969 participants (ages 70 to 89 y) from Olmsted County, MN, using the Clinical Dementia Rating Scale, a neurologic evaluation, and neuropsychologic testing. Data for participants were reviewed for a diagnosis of normal cognition, MCI, or dementia. Clinical components of MetS were ascertained by interview and confirmed from the medical records; biochemical measurements were assayed from a blood draw. We compared 88 na-MCI cases and 241 a-MCI cases with 1640 cognitively normal participants. MetS was not associated with either na-MCI or a-MCI. High C-reactive protein (CRP; highest tertile vs lowest tertile) was associated with na-MCI [odds ratio (OR)=1.85; 95% confidence interval (CI)=1.05, 3.24] but not with a-MCI, after adjusting for sex, age, and years of education. The combination of MetS and high CRP (compared to no MetS and lowest CRP tertile) was associated with na-MCI (OR=2.31; 95% CI=1.07, 5.00), but not with a-MCI (OR=0.96; 95% CI=0.59, 1.54). The combined presence of MetS and high levels of inflammation is associated with na-MCI in this elderly cohort, and suggests etiologic differences in MCI subtypes.

Coronary heart disease is associated with non-amnestic mild cognitive impairment.

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.