To investigate the effect of intellectual and physical activity on biomarkers of Alzheimer’s disease (AD) pathophysiology and cognition in a non-demented elderly population. The biomarkers evaluated were brain Aβ-amyloid load via PIB-PET, neuronal dysfunction via FDG-PET and neurodegeneration via Structural-MRI.
We studied 515 non-demented (428 cognitively normal and 87 MCI) participants in the population based Mayo Clinic Study of Aging who completed a 3T MRI, PET scans, APOE genotype, had lifestyle activity measures and cognition data available. The imaging measures computed were global PiB-PET uptake; global FDG-PET and MRI based hippocampal volume. We consolidated activity variables into lifetime intellectual, current intellectual and current physical activities. We used a global cognitive Z-score as a measure of cognition. We applied two independent methods – partial correlation analysis adjusted for age and gender and path analysis using structural equations to evaluate the associations between lifestyle activities, imaging biomarkers and global cognition.
None of the lifestyle variables correlated with the biomarkers and the path associations between lifestyle variables and biomarkers were not significant (p>0.05). On the other hand, all the biomarkers were correlated with global cognitive Z-score (p<0.05) and the path associations between (lifetime and current) intellectual activities and global Z-score were significant (p<0.01).
Intellectual and physical activity lifestyle factors were not associated with AD biomarkers but intellectual lifestyle factors explained variability in the cognitive performance in this non-demented population. This study provides evidence that lifestyle activities may delay the onset of dementia but do not significantly influence the expression of AD pathophysiology.
Alzheimer’s disease; Imaging biomarkers; Lifestyle Activities
To determine whether MRI measurements observed in the Alzheimer's Disease Neuroimaging Initiative (ADNI; convenience-sample) differ from those observed in the Mayo Clinic Study of Aging (MCSA; population-based sample).
Comparison of two samples.
59 recruiting sites for the ADNI in US/Canada, and the MCSA, a population-based cohort in Olmsted County, MN.
Cognitively normal (CN) subjects and amnestic mild cognitive impairment (aMCI) subjects were selected from the ADNI convenience cohort and MCSA population-based cohort. Two samples were selected; the first was a simple random sample of subjects from both cohorts in the same age range, and the second applied matching for age, sex, education, apolipoprotein E genotype, and Mini-Mental State Examination.
Main outcome measures
Baseline hippocampal volumes and annual percent decline in hippocampal volume.
In the population-based sample, MCSA subjects were older, less educated, performed worse on MMSE, and less often had family history of AD than ADNI subjects. Baseline hippocampal volumes were larger in ADNI compared to MCSA CN subjects in the random sample, although no differences were observed after matching. Rates of decline in hippocampal volume were greater in ADNI compared to MCSA for both CN and aMCI, even after matching.
Rates of decline in hippocampal volume suggest that ADNI subjects have more aggressive brain pathology than MCSA subjects, and hence may not be representative of the general population. These findings have implications for treatment trials that employ ADNI-like recruitment mechanisms and for studies validating new diagnostic criteria for AD in its various stages.
A workgroup commissioned by the Alzheimer’s Association (AA) and the National Institute on Aging (NIA) recently published research criteria for preclinical Alzheimer’s disease (AD). We performed a preliminary assessment of these guidelines.
We employed Pittsburgh compound B positron emission tomography (PET) imaging as our biomarker of cerebral amyloidosis and 18fluorodeoxyglucose PET imaging and hippocampal volume as biomarkers of neurodegeneration. A group of 42 clinically diagnosed AD subjects was used to create imaging biomarker cut-points. A group of 450 cognitively normal (CN) subjects from a population based sample was used to develop cognitive cut-points and to assess population frequencies of the different preclinical AD stages using different cut-point criteria.
The new criteria subdivide the preclinical phase of AD into stages 1–3. To classify our CN subjects, two additional categories were needed. Stage 0 denotes subjects with normal AD biomarkers and no evidence of subtle cognitive impairment. Suspected Non-AD Pathophysiology (SNAP) denotes subjects with normal amyloid PET imaging, but abnormal neurodegeneration biomarker studies. At fixed cut-points corresponding to 90% sensitivity for diagnosing AD and the 10th percentile of CN cognitive scores, 43% of our sample was classified as stage 0; 16% stage 1; 12 % stage 2; 3% stage 3; and 23% SNAP.
This cross-sectional evaluation of the NIA-AA criteria for preclinical AD indicates that the 1–3 staging criteria coupled with stage 0 and SNAP categories classify 97% of CN subjects from a population-based sample, leaving just 3% unclassified. Future longitudinal validation of the criteria will be important.
REM 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) or Parkinson’s disease (PD). There is no data on such risk in a population-based sample.
Cognitively normal subjects aged 70–89 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, PD among the exposed (pRBD+) and unexposed (pRBD−) cohorts.
Forty-four subjects with pRBD+ 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 one 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 (95%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).
In this population-based cohort study, we observed that pRBD confers a 2.2-fold increased risk of developing MCI / PD over four years.
sleep disorders; parasomnias; dementia; Alzheimer’s disease; dementia with Lewy bodies; parkinsonism; synuclein
To study the frequencies of chronic viral hepatitis B (HBV), hepatitis C (HCV), and their associations with hepatocellular carcinoma (HCC) in immigrant Somalis seen at Mayo Clinic, Rochester, Minnesota.
We investigated the frequencies of HBV and HCV infection and HCC in immigrant Somalis seen at Mayo Clinic, Rochester, Minnesota between July 1, 1996 and October 31, 2009. Non-Somali Olmsted County residents served as controls.
For Somali males and females, age-adjusted proportions (per 1000) were 209 and 123 for HBV surface antigen (HBsAg), 644 and 541 for HBV core antibody (HBcAb) and 99 and 66 for anti-HCV. The comparative proportions in non-Somalis were 20 and 9 for HBsAg, 126 and 97 for HBcAb, and 32 and 17 for anti-HCV. HCV RNA confirmed that 93% (68/73) of Somalis and 93% (282/303) of non-Somalis with positive anti-HCV tests had active HCV infection. Of 30 Somali patients with HCC, 22 (75.9%) were anti-HCV-positive [odds ratio (95% CI): 31.3 (12.95 – 75.52), p<0.0001 compared to anti-HCV-negative Somalis]; 5 (17.9%) were HBsAg-positive [OR 1.38 (0.52–3.69), p=0.53]; and 18 (69.2%) were HBcAb-positive [OR 1.80 (0.77–4.20), p=0.16]. Viral hepatitis was diagnosed coincident with HCC in 45% (9/20) of HCV-associated HCCs. Only 20% (4/20) of HCCs were detected during surveillance.
HBV and HCV occurred frequently in this sample of Somali immigrants. HCV was the major risk factor for HCC. Screening Somali immigrants for HCV infection may enhance the prevention, early detection, and optimal treatment of HCC.
Somali; Hepatitis C; Hepatitis B; Hepatocellular carcinoma
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 [HR], [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.
Mild cognitive impairment; dementia; dietary proteins; dietary fats; dietary carbohydrates; caloric intake; energy intake; prospective studies; community-based
There are many challenges for determining the prevalence and incidence of frontotemporal lobar degenerations (FTLD). Consequently, the number of cases of behavioral variant frontotemporal dementia (bvFTD) or primary progressive aphasia (PPA) in the USA is unknown. Our objective was to derive a consensus estimate of bvFTD and PPA prevalence and thereby to estimate the total number of these syndromes in the USA. We identified five prevalence and three incidence studies of FTLD based on passive surveillance and seven studies of survival in FTLD. Data from these studies were used to estimate the number of cases of PPA or bvFTD in the USA. Because prevalence and incidence estimates outside of the 45–64-year age range were either not available or widely divergent, we used data from clinical and pathological series to estimate the proportion of FTLD cases aged <45 or >64 years. The prevalence estimates in the age categories of 45–64 years old have ranged from 15 to 22 per 100,000 person-years in studies where both bvFTD and PPA were identified. The incidence estimates for the same age group ranged from 2.7 to 4.1 per 100,000 person-years. Using a survival rate of 6 to 9 years from onset and rates from the incidence studies, a calculated prevalence estimate (prevalence = incidence × duration) was similar to the previously reported prevalence rates. We estimated that 10% of cases were less than age 45 years and 30% were 65 years and older. We estimate that there are approximately 20,000 to 30,000 cases of the cognitive syndromes of FTLD in the USA. The main threat to the accuracy of the estimates is the difficulty in diagnosing the clinical syndromes that comprise the FTLD group of disorders.
Frontotemporal lobar degeneration; Prevalence; Incidence
To examine the association between computer use, physical exercise, aging, and mild cognitive impairment (MCI).
Patients and 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.
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).
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.
CDR, Clinical Dementia Rating; CI, confidence interval; MCI, mild cognitive impairment; OR, odds ratio
To study the frequencies of chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, and their associations with hepatocellular carcinoma (HCC) in immigrant Somalis seen at Mayo Clinic in Rochester, Minnesota.
Patients and Methods
We determined the frequencies of HBV and HCV infection and HCC in immigrant Somalis seen at Mayo Clinic from July 1, 1996, through October 31, 2009. Non-Somali Olmsted County residents served as controls.
For Somali males and females, age-adjusted proportions (per 1000 population) were 209 and 123 for hepatitis B surface antigen (HBsAg), 644 and 541 for hepatitis B core antibody (HBcAb), and 99 and 66 for anti-HCV. The comparative proportions in non-Somalis were 20 and 9 for HBsAg, 126 and 97 for HBcAb, and 32 and 17 for anti-HCV. Hepatitis C virus RNA confirmed that 68 of 73 Somalis (93.2%) and 261 of 282 non-Somalis (92.6%) with positive anti-HCV test results had active HCV infection. Of 30 Somali patients with HCC, 22 (73.3%) tested anti-HCV positive (odds ratio [OR], 31.3; 95% confidence interval [CI], 13.0-75.5; P<.001; compared with anti-HCV–negative Somalis), 5 (16.7%) were HBsAg positive (OR, 1.4; 95% CI, 0.5-3.7; P=.53), and 18 (60.0%) were HBcAb positive (OR, 1.8; 95% CI, 0.8-4.2; P=.16). Viral hepatitis was diagnosed coincident with HCC in 9 of 20 patients (45.0%) with HCV-associated HCCs. Only 4 of 24 cases of HCC (16.7%) were detected during surveillance.
Both HBV and HCV occurred frequently in this sample of Somali immigrants. However, HCV was the major risk factor for HCC. Screening Somali immigrants for HCV infection may enhance the prevention, early detection, and optimal treatment of HCC.
We investigated whether engaging in cognitive activities is associated with mild cognitive impairment (MCI) in a cross-sectional study derived from an ongoing population-based study of normal cognitive aging and MCI in Olmsted County, Minnesota. A random sample of 1321 non-demented study participants ages 70 to 89 (n = 1124 cognitively normal persons and n = 197 subjects with MCI) was interviewed about the frequency of cognitive activities carried out in late life (within one year of the date of interview). Computer activities [OR (95% CI) = 0.50 (0.36, 0.71); p < .0001)], craft activities such as knitting, quilting, etc. [0.66 (0.47, 0.93); p = 0.019)], playing games [0.65 (0.47, 0.90); p = 0.010)], and reading books [0.67 (0.49, 0.94); p = 0.019)] were associated with decreased odds of having MCI. Social activities such as traveling were marginally significant [0.71 (0.51, 1.00); p = 0.050)]. Even though the point estimates for reading magazines, playing music, artistic activities, and group activities were associated with reduced odds of having MCI, none reached statistical significance. We could not expect to observe any difference between the two groups on the variable of reading newspapers since almost identical proportions of the two groups (97.4% of normals and 97.5% of the MCI group) were engaged in reading newspapers on a regular basis.
cognitive activities; aging; mild cognitive impairment
To investigate the association of type 2 diabetes with subcortical infarctions.
RESEARCH DESIGN AND METHODS
We investigated this association in subjects with type 2 diabetes (case subjects; n = 93) and without type 2 diabetes (control subjects; n = 186), matched by age, sex, and years of education. Participants were a subset of the Mayo Clinic Study of Aging (median age 79 years) who had undergone magnetic resonance imaging.
The frequency of subcortical infarctions was 39% in case subjects and 29% in control subjects (odds ratio 1.59 [95% CI 0.91–2.75]). The association was stronger in case subjects without treatment (2.60 [1.11–6.08]) and in case subjects with diabetes-related complications (1.96 [1.02–3.74]) compared with control subjects.
These findings suggest that untreated type 2 diabetes and type 2 diabetes with complications are associated with subcortical infarctions.
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 ε4 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.
Cognitive impairment; Coronary heart disease; Myocardial infarction; Angina; Coronary artery bypass grafting; Population-based
To investigate associations of the Mediterranean diet (MeDi) components and the MeDi score with mild cognitive impairment (MCI).
Participants (aged 70–89 years) were clinically evaluated to assess MCI and dementia, and completed a 128-item food frequency questionnaire.
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].
Vegetables, unsaturated fats, and a high MeDi score may be beneficial to cognitive function.
Mild cognitive impairment; Dietary intake; Moderate alcohol intake; Unsaturated fatty acids; Mediterranean diet; Longitudinal; Prevalence studies; Incidence studies; Population-based
In the past 10 years, there has been a virtual explosion in the literature concerning the construct of mild cognitive impairment. The interest in this topic demonstrates the increasing emphasis on the identification of the earliest features of cognitive disorders such as Alzheimer’s disease and other dementias. Mild cognitive impairment represents the earliest clinical features of these conditions and, hence, has become a focus of clinical, epidemiological, neuroimaging, biomarker, neuropathological, disease mechanism and clinical trials research. This review summarizes the progress that has been made while also recognizing the challenges that remain.
Mild cognitive impairment; Alzheimer’s disease; Imaging; Cognitive decline
Defining the nature of the contribution of stroke to cognitive impairment remains challenging.
We randomly selected Olmsted County, MN residents aged 70–89 years on October 1, 2004 and invited eligible non-demented subjects to participate. Participants (n = 2,050) were evaluated with an informant interview, a neurological evaluation, and neuropsychological testing. Neuropsychological testing included 9 tests to assess memory, attention and executive function, visuospatial cognition and language. Subjects were diagnosed by consensus as cognitively normal, MCI (either amnestic (a-) or non-amnestic (na-)), or dementia. A history of stroke was obtained from the subject and confirmed in the medical record. We computed the odds ratios (OR) for a clinical diagnosis of MCI or for scoring in the lowest quartile on each cognitive domain.
There were 1640 cognitively normal and 329 MCI subjects, 241 a-MCI and 88 na-MCI. In fully adjusted models with non-demented subjects only, a history of stroke was associated with a higher odds ratio (OR) of na-MCI (OR= 2.85, 95% CI 1.61 – 5.04) than a-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 e4 genotype was associated only with a-MCI and with impaired memory function.
In this population-based sample of non-demented persons, a history of stroke was particularly associated with na-MCI and with impairment in non-memory cognition. APOE e4 genotype was associated with memory impairment and a-MCI.
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 non-amnestic [na-MCI]). We studied a randomly selected sample of 1969 subjects (ages 70 to 89 years) from Olmsted County, MN, using the Clinical Dementia Rating Scale, a neurological evaluation, and neuropsychological 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 subjects. 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.
metabolic syndrome; insulin resistance; mild cognitive impairment; C-reactive protein; inflammation; cross-sectional study
The telephone assessment of cognitive functions may reduce the cost and burden of epidemiological studies.
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.
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 ≤31 as the optimal cutoff score to separate subjects with MCI from subjects with normal cognition (sensitivity = 71.4%; subjects with dementia excluded), and ≤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%).
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.
Dementia; Mild cognitive impairment; Telephone Interview for Cognitive Status-modified
Physical exercise was found to be associated with a decreased risk of dementia and Alzheimer disease. We investigated whether physical exercise is also associated with mild cognitive impairment (MCI).
Population-based case-control study.
The Mayo Clinic Study of Aging, an ongoing population-based cohort study in Olmsted County, Minnesota, USA.
1324 non-demented subjects who completed a questionnaire on physical exercise.
Main Outcome Measures
An expert consensus panel classified each subject as either cognitively normal or affected by MCI using information from a Clinical Dementia Rating Scale administered to the subject and to an informant, a neurological evaluation, and neuropsychological testing to assess 4 cognitive domains.
We compared the frequency of physical exercise in 198 subjects with MCI to the frequency in 1126 cognitively normal subjects and adjusted analyses for age, sex, years of education, medical comorbidity, and depression. The odds ratio (OR) for any frequency of moderate-intensity exercise was 0.61 (95% confidence interval [CI], 0.43–0.88; P=.008) for exercise in midlife (aged 50–65 years), and 0.68 (95% CI, 0.49–0.93; P=.02) for exercise in late life. The findings were consistent in men and women. Light exercise and vigorous exercise were not significantly associated with MCI.
In this population-based case-control study, any frequency of moderate-intensity exercise carried out in either midlife or late life was associated with a reduced OR of MCI.
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 ≥ 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.
Cross-sectional studies; dietary fats; polyunsaturated fatty acids; monounsaturated fatty acids; population-based; mild cognitive impairment
Inflammation is suggested to play a role in the development of Alzheimer’s disease, and may also be involved in the pathogenesis of mild cognitive impairment (MCI). This study examined the association of inflammatory markers in serum or plasma with prevalent MCI and MCI subtypes in a population-based sample.
Olmsted County, MN, residents aged 70–89 years on October 1, 2004, were evaluated using the Clinical Dementia Rating Scale, a neurological evaluation, and neuropsychological testing. Information ascertained for each participant was reviewed by an expert panel of neuropsychologists, physicians, and nurses, and a diagnosis of normal cognition, MCI, or dementia was made by consensus. C-reactive protein (CRP), interleukin 6 (IL-6), tumor necrosis alpha (TNFα), and adiponectin were measured at baseline.
Among 313 subjects with MCI and 1,570 cognitively normal subjects, a CRP level in the upper quartile (> 3.3 mg/L) was significantly associated with MCI (odds ratio [OR], 1.42; 95% confidence interval [CI], 1.00–2.01) and with non-amnestic MCI (na-MCI; OR, 2.05; 95% CI, 1.12–3.78) after adjusting for age, sex, and years of education. However, there was no association with amnestic MCI (a-MCI; OR, 1.21; 95% CI, 0.81–1.82). No association was observed with the other inflammatory markers.
Plasma CRP is associated with prevalent MCI and with na-MCI in elderly, non-demented persons in the population-based setting. These findings suggest an involvement of inflammation in the pathogenesis of MCI.
C-reactive protein; Interleukin 6; Adiponectin; Inflammation; Cytokines; Mild cognitive impairment; Cross-sectional; Population-based
Little is known about the population-based prevalence of neuropsychiatric symptoms in mild cognitive impairment (MCI).
To estimate the prevalence of neuropsychiatric symptoms in MCI and normal cognitive aging in a defined population.
Cross-sectional study derived from an ongoing population-based prospective cohort study.
The Mayo Clinic Study of Aging.
We studied a random sample of 1969 non-demented participants out of the target population of 9965 elderly persons residing in Olmsted County on the prevalence date (October 1, 2004). Neuropsychiatric data were available on 319 of the 329 MCI subjects (97.0%) and on 1590 of the 1640 cognitively normal subjects (97.0%).
Neurological, cognitive, and neuropsychiatric data were gathered from the study participants. A classification of normal cognitive aging, MCI, and dementia was adjudicated by an expert consensus panel. Accordingly, 329 subjects were classified as having MCI and the remaining 1640 subjects were classified as cognitively normal.
Main Outcome Measure
The Neuropsychiatric Inventory Questionnaire (NPI-Q).
Multi-variable logistic regression analyses were conducted, after adjusting for age, sex, and education. By taking into consideration both the odds ratio and the frequency of a symptom, the most distinguishing features between the 2 groups were apathy (odds ratio [OR], 4.53; 95% confidence interval [95% CI], 3.11–6.60; P<.001), agitation (OR, 3.60; 95% CI, 2.18–5.92; P<.001), anxiety (OR, 3.00; 95% CI, 2.01–4.48; P<.001), irritability (OR, 2.99; 95% CI, 2.11–4.22; P<.001), and depression (OR, 2.78; 95% CI, 2.06–3.76; P<.001). Delusion had the highest OR (8.12; 95% CI, 2.92–22.60; P<.001); however, it was rare in both cognitively normal subjects (6/1590=0.4%) and MCI (11/319=3.4%). Thus, the population attributable risk for delusion was only 2.62% as compared to 14.60% for apathy.
Non-psychotic symptoms affected approximately 50% of subjects with MCI and 25% of cognitively normal subjects. By contrast, psychotic symptoms were rare.
It remains unknown whether diabetes mellitus is a risk factor for mild cognitive impairment (MCI).
To investigate the association of diabetes mellitus with MCI using a population-based case-control design.
Design, Setting, and Participants
Our study was conducted in subjects aged 70 through 89 years on October 1, 2004, who were randomly selected from the Olmsted County, MN, population.
Main Outcome Measure
We administered to all participants the Clinical Dementia Rating Scale, a neurological exam, and a neuropsychological evaluation including 9 tests in 4 cognitive domains to diagnose normal cognition, MCI, or dementia. We assessed history of diabetes, diabetes treatment, and complications by interview and we measured fasting blood glucose. History of diabetes was also confirmed using a medical records-linkage system.
We compared 329 patients with MCI to 1640 subjects free of MCI and of dementia. The frequency of diabetes was similar in subjects with MCI (20.1%) and in subjects without MCI (17.7%; odds ratio [OR], 1.16; 95% confidence interval [CI], 0.85-1.57). However, MCI was associated with onset of diabetes before age 65 years (OR, 2.20; 95% CI, 1.29-3.73), diabetes duration ≥10 years (OR, 1.76; 95% CI, 1.16-2.68), treatment with insulin (OR, 2.01; 95% CI, 1.22-3.31), and presence of complications (OR, 1.80; 95% CI, 1.13-2.89) after adjustment for age, sex, and education. Analyses using alternative definitions of diabetes yielded consistent findings.
These findings suggest an association between earlier onset, longer duration, and greater severity of diabetes and MCI.
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.
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.
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.
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.
Cognitive impairment; Prevalence; Incidence; Risk factors; Cohort studies; Data collection instruments
Reasons for attrition in studies vary, but may be a major concern in long-term studies if those who drop out differ systematically from those who continue to participate. Factors associated with dropout were evaluated in a twelve-year community-based, prospective cohort study of urologic disease in men.
During 1989–1991, 2,115 randomly selected Caucasian men, ages 40–79 years from Olmsted County, Minnesota were enrolled and followed with questionnaires biennially; 332 men were added in follow-up. A random subset (~25%) received a urologic examination. Baseline characteristics including age, benign prostatic hyperplasia (BPH) symptoms, comorbidities, and socioeconomic factors were compared between subjects who did and did not participate after the twelfth year of follow-up.
Of the 2,447 men, 195 died and were excluded; 682 did not participate in 2002. Compared with men in the 40–49 year age group, men ≥ 70 years of age at baseline had a greater relative odds of dropout, 2.65 (95% CI: 1.93, 3.63). In age-adjusted analyses, relative to men without stroke, men who had suffered a stroke had a higher odds of dropout, age-adjusted OR 3.07 (95% CI: 1.49, 6.33). Presence of at least one BPH symptom was not associated with dropout, (age-adjusted OR 1.12 (95% CI: 0.93, 1.36)).
These results provide assurance that dropout was not related to primary study outcomes. However, factors associated with dropout should be taken into account in analyses where they may be potential confounders.
A large number of longitudinal studies of population-based ageing cohorts are in progress internationally, but the insights from these studies into the risk and protective factors for cognitive ageing and conditions like mild cognitive impairment and dementia have been inconsistent. Some of the problems confounding this research can be reduced by harmonising and pooling data across studies. COSMIC (Cohort Studies of Memory in an International Consortium) aims to harmonise data from international cohort studies of cognitive ageing, in order to better understand the determinants of cognitive ageing and neurocognitive disorders.
Longitudinal studies of cognitive ageing and dementia with at least 500 individuals aged 60 years or over are eligible and invited to be members of COSMIC. There are currently 17 member studies, from regions that include Asia, Australia, Europe, and North America. A Research Steering Committee has been established, two meetings of study leaders held, and a website developed. The initial attempts at harmonising key variables like neuropsychological test scores are in progress.
The challenges of international consortia like COSMIC include efficient communication among members, extended use of resources, and data harmonisation. Successful harmonisation will facilitate projects investigating rates of cognitive decline, risk and protective factors for mild cognitive impairment, and biomarkers of mild cognitive impairment and dementia. Extended implications of COSMIC could include standardised ways of collecting and reporting data, and a rich cognitive ageing database being made available to other researchers. COSMIC could potentially transform our understanding of the epidemiology of cognitive ageing, and have a world-wide impact on promoting successful ageing.
Cohort studies; Cognitive ageing; Data harmonisation; Dementia; International consortium; Mild cognitive impairment