Rosebud O. Roberts

Mild Cognitive Impairment: Ten Years Later

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 disease and other dementias. Mild cognitive impairment represents the earliest clinical features of these conditions and, hence, has become a focus of clinical, epidemiologic, 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.

Natural History of Prostatism: Risk Factors for Acute Urinary Retention

PURPOSE We determined the occurrence of and risk factors for acute urinary retention in the community setting. MATERIALS AND METHODS A cohort of 2,115 men 40 to 79 years old was randomly selected from an enumeration of the Olmsted County, Minnesota population (55% response rate). Participants completed a previously validated baseline questionnaire that assessed symptom severity, and voided into a portable urometer to measure peak urinary flow rates. A 25% random subsample underwent transrectal sonographic imaging of the prostate to determine prostate volume. Followup was performed through a retrospective review of community medical records to determine the occurrence of acute urinary retention in the subsequent 4 years. RESULTS During the 8,344 person-years of followup 57 men had a first episode of acute urinary retention (incidence 6.8/1,000 person-years, 95% confidence interval [CI] 5.2, 8.9). Among men with no to mild symptoms (American Urological Association symptom index score 7 or less) the incidence of acute urinary retention increased from 2.6/1,000 person-years among men 40 to 49 years old to 9.3/1,000 person-years among men 70 to 79 years old. By contrast, rates increased from 3.0/1,000 person-years for men 40 to 49 years old to 34.7/1,000 person-years among men 70 to 79 years old among men with moderate to severe symptoms (American Urological Association symptom index score greater than 7). Men with depressed peak urinary flow rate (less than 12 ml. per second) were at 4 times the risk of acute urinary retention compared with men with urinary flow rates greater than 12 ml. per second (95% CI 2.3, 6.6). Men with an enlarged prostate (greater than 30 ml.) experienced a 3-fold increase in risk (95% CI 1.0, 9.0, p = 0.04). CONCLUSIONS Lower urinary tract symptoms, depressed peak urinary flow rates, enlarged prostates and older age are associated with an increased risk of acute urinary retention in community dwelling men. These findings may help to identify men at increased risk of acute urinary retention in whom closer evaluation may be warranted.

An operational approach to National Institute on Aging–Alzheimer's Association criteria for preclinical Alzheimer disease

A workgroup commissioned by the Alzheimers Association (AA) and the National Institute on Aging (NIA) recently published research criteria for preclinical Alzheimer disease (AD). We performed a preliminary assessment of these guidelines.

Insulin-like Growth Factor I, Insulin-like Growth Factor Binding Protein 3, and Urologic Measures of Benign Prostatic Hyperplasia

Laboratory studies suggest that insulin-like growth factor I (IGF-I) promotes prostatic growth. The authors evaluated the association between benign prostatic hyperplasia and IGF-I and its binding protein IGFBP-3 in community-dwelling men to determine whether this laboratory finding is manifest at the population level. Participants (n = 471) were Olmsted County, Minnesota, Caucasian males aged 40-79 years in 1990. Urologic measures were assessed from the International Prostate Symptom Score, peak urinary flow rates, prostate volume, and serum prostate-specific antigen (PSA), and serum IGF-I and IGFBP-3 levels were measured. After adjustment for age, the relative odds (odds ratios) of an abnormal urologic measure in men with high versus low serum IGF-I levels were 0.98 (95% confidence interval (CI): 0.66, 1.45) for a symptom score of >7, 1.14 (95% CI: 0.72, 1.80) for a peak urinary flow rate of <12 ml/second, 1.11 (95% CI: 0.72, 1.72) for a prostate volume of >30 ml, and 0.71 (95% CI: 0.46, 1.09) for a PSA level of >1.4 ng/ml. A low IGFBP-3 level was associated with an enlarged prostate (odds ratio = 1.72, 95% CI: 1.05, 2.82), after simultaneous adjustment for IGF-I and age, but not with other urologic measures. These data do not provide evidence for an association between benign prostatic hyperplasia and serum IGF-I.

Prevalence of mild cognitive impairment is higher in men The Mayo Clinic Study of Aging

Objective: We investigated the prevalence of mild cognitive impairment (MCI) in Olmsted County, MN, using in-person evaluations and published criteria. Methods: We evaluated an age- and sex-stratified random sample of Olmsted County residents who were 70–89 years old on October 1, 2004, using the Clinical Dementia Rating Scale, a neurologic evaluation, and neuropsychological testing to assess 4 cognitive domains: memory, executive function, language, and visuospatial skills. Information for each participant was reviewed by an adjudication panel and a diagnosis of normal cognition, MCI, or dementia was made using published criteria. Results: Among 1,969 subjects without dementia, 329 subjects had MCI, with a prevalence of 16.0% (95% confidence interval [CI] 14.4–17.5) for any MCI, 11.1% (95% CI 9.8–12.3) for amnestic MCI, and 4.9% (95% CI 4.0–5.8) for nonamnestic MCI. The prevalence of MCI increased with age and was higher in men. The prevalence odds ratio (OR) in men was 1.54 (95% CI 1.21–1.96; adjusted for age, education, and nonparticipation). The prevalence was also higher in subjects who never married and in subjects with an APOE ε3ε4 or ε4ε4 genotype. MCI prevalence decreased with increasing number of years of education (p for linear trend <0.0001). Conclusions: Our study suggests that approximately 16% of elderly subjects free of dementia are affected by MCI, and amnestic MCI is the most common type. The higher prevalence of MCI in men may suggest that women transition from normal cognition directly to dementia at a later age but more abruptly.

Physical Exercise, Aging, and Mild Cognitive Impairment: A Population-Based Study

BACKGROUND Physical exercise is associated with decreased risk of dementia and Alzheimer disease. OBJECTIVE To investigate whether physical exercise is associated with decreased risk of mild cognitive impairment (MCI). DESIGN Population-based case-control study. SETTING The Mayo Clinic Study of Aging, an ongoing population-based cohort study in Olmsted County, Minnesota. PARTICIPANTS A total of 1324 subjects without dementia who completed a Physical Exercise Questionnaire. MAIN OUTCOME MEASURES An expert consensus panel classified each subject as having normal cognition or MCI based on published criteria. RESULTS We compared the frequency of physical exercise among 198 subjects with MCI with that among 1126 subjects with normal cognition and adjusted the analyses for age, sex, years of education, medical comorbidity, and depression. The odds ratios for any frequency of moderate exercise were 0.61 (95% confidence interval, 0.43-0.88; P = .008) for midlife (age range, 50-65 years) and 0.68 (95% confidence interval, 0.49-0.93; P = .02) for late life. The findings were consistent among men and women. Light exercise and vigorous exercise were not significantly associated with decreased risk of MCI. CONCLUSION In this population-based case-control study, any frequency of moderate exercise performed in midlife or late life was associated with a reduced odds of having MCI.

Prevalence of Neuropsychiatric Symptoms in Mild Cognitive Impairment and Normal Cognitive Aging : Population-Based Study

CONTEXT Little is known about the population-based prevalence of neuropsychiatric symptoms in mild cognitive impairment (MCI). OBJECTIVE To estimate the prevalence of neuropsychiatric symptoms in MCI and normal cognitive aging in a defined population. DESIGN Cross-sectional study derived from an ongoing population-based prospective cohort study. SETTING The Mayo Clinic Study of Aging. PARTICIPANTS We studied a random sample of 1969 individuals without dementia from the target population of 9965 elderly persons residing in Olmsted County (Minnesota) on the prevalence date (October 1, 2004). Neuropsychiatric data were available for 319 of 329 subjects with MCI (97.0%) and 1590 of 1640 subjects with normal cognition (97.0%). Neurologic, cognitive, and neuropsychiatric data were obtained from the study participants. A classification of MCI, dementia, and normal cognitive aging was adjudicated by an expert consensus panel. Accordingly, 329 subjects were classified as having MCI and the remaining 1640 subjects were classified as having normal cognition. MAIN OUTCOME MEASURE Neuropsychiatric Inventory Questionnaire score. RESULTS Multivariate logistic regression analyses were conducted after adjusting for age, sex, and educational status. By considering both the odds ratio (OR) and the frequency of a symptom, the most distinguishing features between the 2 groups were apathy (OR, 4.53; 95% confidence interval [CI], 3.11-6.60; P < .001), agitation (3.60; 2.18-5.92; P < .001), anxiety (3.00; 2.01-4.48; P < .001), irritability 2.99; 2.11-4.22; P < .001), and depression (2.78; 2.06-3.76; P < .001). The OR was highest for delusion (8.12; 95% CI, 2.92-22.60; P < .001); however, it was rare in both subjects with MCI (11 of 319 [3.4%]) and those with normal cognition (6 of 1590 [0.4%]). Thus, the population attributable risk for delusion was only 2.62% compared with 14.60% for apathy. CONCLUSIONS Nonpsychotic symptoms affected approximately 50% of subjects with MCI and 25% of subjects with normal cognition. In contrast, psychotic symptoms were rare.

Association of Mediterranean Diet with Mild Cognitive Impairment and Alzheimer's Disease: A Systematic Review and Meta-Analysis

BACKGROUND/OBJECTIVE To conduct a systematic review of all studies to determine whether there is an association between the Mediterranean diet (MeDi) and cognitive impairment. METHODS We conducted a comprehensive search of the major databases and hand-searched proceedings of major neurology, psychiatry, and dementia conferences through November 2012. Prospective cohort studies examining the MeDi with longitudinal follow-up of at least 1 year and reporting cognitive outcomes (mild cognitive impairment [MCI] or Alzheimers disease [AD]) were included. The effect size was estimated as hazard-ratio (HR) with 95% confidence intervals (CIs) using the random-effects model. Heterogeneity was assessed using Cochrans Q-test and I2-statistic. RESULTS Out of the 664 studies screened, five studies met eligibility criteria. Higher adherence to the MeDi was associated with reduced risk of MCI and AD. The subjects in the highest MeDi tertile had 33% less risk (adjusted HR = 0.67; 95% CI, 0.55-0.81; p < 0.0001) of cognitive impairment (MCI or AD) as compared to the lowest MeDi score tertile. Among cognitively normal individuals, higher adherence to the MeDi was associated with a reduced risk of MCI (HR = 0.73; 95% CI, 0.56-0.96; p = 0.02) and AD (HR = 0.64; 95% CI, 0.46-0.89; p = 0.007). There was no significant heterogeneity in the analyses. CONCLUSIONS While the overall number of studies is small, pooled results suggest that a higher adherence to the MeDi is associated with a reduced risk of developing MCI and AD, and a reduced risk of progressing from MCI to AD. Further prospective-cohort studies with longer follow-up and randomized controlled trials are warranted to consolidate the evidence. Systematic review registration number: PROSPERO 2013: CRD42013003868.

Short-term clinical outcomes for stages of NIA-AA preclinical Alzheimer disease

Objective: Recommendations for the diagnosis of preclinical Alzheimer disease (AD) have been formulated by a workgroup of the National Institute on Aging and Alzheimers Association. Three stages of preclinical AD were described. Stage 1 is characterized by abnormal levels of β-amyloid. Stage 2 represents abnormal levels of β-amyloid and evidence of brain neurodegeneration. Stage 3 includes the features of stage 2 plus subtle cognitive changes. Stage 0, not explicitly defined in the criteria, represents subjects with normal biomarkers and normal cognition. The ability of the recommended criteria to predict progression to cognitive impairment is the crux of their validity. Methods: Using previously developed operational definitions of the 3 stages of preclinical AD, we examined the outcomes of subjects from the Mayo Clinic Study of Aging diagnosed as cognitively normal who underwent brain MRI or [18F]fluorodeoxyglucose and Pittsburgh compound B PET, had global cognitive test scores, and were followed for at least 1 year. Results: Of the 296 initially normal subjects, 31 (10%) progressed to a diagnosis of mild cognitive impairment (MCI) or dementia (27 amnestic MCI, 2 nonamnestic MCI, and 2 non-AD dementias) within 1 year. The proportion of subjects who progressed to MCI or dementia increased with advancing stage (stage 0, 5%; stage 1, 11%; stage 2, 21%; stage 3, 43%; test for trend, p < 0.001). Conclusions: Despite the short follow-up period, our operationalization of the new preclinical AD recommendations confirmed that advancing preclinical stage led to higher proportions of subjects who progressed to MCI or dementia.

Assessing the Temporal Relationship Between Cognition and Gait: Slow Gait Predicts Cognitive Decline in the Mayo Clinic Study of Aging

BACKGROUND The association between gait speed and cognition has been reported; however, there is limited knowledge about the temporal associations between gait slowing and cognitive decline among cognitively normal individuals. METHODS The Mayo Clinic Study of Aging is a population-based study of Olmsted County, Minnesota, United States, residents aged 70-89 years. This analysis included 1,478 cognitively normal participants who were evaluated every 15 months with a nurse visit, neurologic evaluation, and neuropsychological testing. The neuropsychological battery used nine tests to compute domain-specific (memory, language, executive function, and visuospatial skills) and global cognitive z-scores. Timed gait speed (m/s) was assessed over 25 feet (7.6 meters) at a usual pace. Using mixed models, we examined baseline gait speed (continuous and in quartiles) as a predictor of cognitive decline and baseline cognition as a predictor of gait speed changes controlling for demographics and medical conditions. RESULTS Cross-sectionally, faster gait speed was associated with better performance in memory, executive function, and global cognition. Both cognitive scores and gait speed declined over time. A faster gait speed at baseline was associated with less cognitive decline across all domain-specific and global scores. These results were slightly attenuated after excluding persons with incident mild cognitive impairment or dementia. By contrast, baseline cognition was not associated with changes in gait speed. CONCLUSIONS Our study suggests that slow gait precedes cognitive decline. Gait speed may be useful as a reliable, easily attainable, and noninvasive risk factor for cognitive decline.