Objective: To determine the rate of progression of mild cognitive impairment (MCI) to dementia with Lewy bodies (DLB). Methods:We followed 337 patients with MCI in the Mayo Alzheimer's Disease Research Center (range 2-12 years). Competing risks survival models were used to examine the rates of progression to clinically probable DLB and Alzheimer disease (AD). A subset of patients underwent neuropathologic examination.Results: In this clinical cohort, 116 remained as MCI, while 49 progressed to probable DLB, 162 progressed to clinically probable AD, and 10 progressed to other dementias. Among nonamnestic MCI, progression rate to probable DLB was 20 events per 100 person-years and to probable AD was 1.6 per 100 person-years. Among amnestic MCI, progression rate to probable AD was 17 events per 100 person-years, and to DLB was 1.5 events per 100 person-years. In 88% of those who developed probable DLB, the baseline MCI diagnosis included attention and/or visuospatial deficits. Those who developed probable DLB were more likely to have baseline daytime sleepiness and subtle parkinsonism. In 99% of the clinically probable AD group, the baseline MCI diagnosis included memory impairment. Neuropathologic confirmation was obtained in 24 of 30 of those with clinically probable AD, and in 14 of 18 of those with clinically probable DLB. Neurodegenerative conditions can evolve for many years before a threshold of neuronal loss is reached that triggers the emergence of clinical signs. Our ability to detect the earliest stage of these conditions is critical for purposes of intervening while neuronal viability is still present. Mild cognitive impairment (MCI) was initially characterized by isolated memory impairment and preserved activities of daily living. It is now well established that amnestic MCI most often represents an early stage of Alzheimer disease (AD), 1,2 with an annual rate of transition in clinical samples ranging from 10% to 17%.3-5 Although much work has been done to examine the predictive value of MCI as it relates to AD, very little is known about the predementia MCI stage of dementia with Lewy bodies (DLB).6-8 The purpose of this study was to determine the clinical characteristics of patients with MCI at increased risk of DLB, and to quantify the annual rate of progression from MCI to probable DLB in a clinical referral sample.When dementia severity is mild or mild to moderate, cognitive comparisons reveal a consistent dissociation between clinically probable AD and DLB. This is characterized by early memory and naming deficits with relatively preserved attention and visuospatial skills in AD, and impaired attention and visuospatial skills with better memory and naming in DLB. [9][10][11] We From the Departments of Psychiatry and Psychology (T

Early recognition of colorectal cancer (CRC) in young patients without known genetic predisposition is a challenge, and clinicopathologic features at time of presentation are not well described. We conducted the current study to review these features in a large population of patients with young-onset CRC (initial diagnosis at age ≤50 yr without established risk factors). We reviewed the records of all patients aged 50 years or younger diagnosed with a primary CRC at our institution between 1976 and 2002. Patients with inflammatory bowel disease, polyposis syndromes, or a known genetic predisposition for CRC were excluded. Data regarding clinical and pathologic features at time of initial presentation were abstracted by trained personnel. We identified 1025 patients, 585 male. Mean age at presentation was 42.4 years (standard deviation 6.4). Eight hundred eighty-six (86%) patients were symptomatic at time of diagnosis. Clinical features in symptomatic patients included rectal bleeding (51%), change in bowel habits (18%), abdominal pain (32%), weight loss (13%), nausea/vomiting (7%), melena (2%), and other (26%). Evaluation of asymptomatic patients was pursued with findings of anemia (14%), positive fecal occult blood test (7%), abdominal mass (2%), mass on digital rectal exam (2%), and other (80%). Site of primary tumor was colonic in 51% and rectal in 49%. Synchronous malignant lesions were noted in 1%. Mucinous and signet cell histology was seen in 11% and 2%, respectively. Tumor grade distribution was grade 1 (2%), grade 2 (54%), grade 3 (34%), and grade 4 (7%). The stage distribution was stage I (13%), stage II (21%), stage III (32%), and stage IV (34%). To our knowledge, the current study is the largest cohort of young-onset CRC patients with no known genetic predisposition for disease. Most patients were symptomatic, had left-colon or rectal cancers and presented with more advanced stage disease. Our findings should promote increased awareness and the aggressive pursuit of symptoms in otherwise young, low-risk patients, as these symptoms may represent an underlying colorectal malignancy.

OBJECTIVES To determine the association of multiple chronic conditions with risk of incident mild cognitive impairment (MCI)/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 and evaluated by a study coordinator, a physician, and underwent neuropsychometric testing at baseline and at 15-month intervals to assess diagnoses of MCI and dementia. We electronically captured information on International Classification of Diseases, ninth revision (ICD-9) codes for chronic conditions in the five years prior to enrollment using the Rochester Epidemiology Project medical records linkage system. We defined multimorbidity as having two or more chronic conditions and examined the association of multimorbidity with MCI/dementia using Cox proportional hazards models. RESULTS Among 2,176 cognitively normal participants (mean [±SD] age 78.5 [±5.2] years; 50.6% men), 1,884 (86.6%) had multimorbidity. The risk of MCI/dementia was elevated in persons with multimorbidity (hazard ratio [HR]: 1.38; 95% confidence interval [CI], 1.05–1.82). The HR was stronger in persons with ≥4 conditions (HR: 1.61; 95%CI, 1.21–2.13) compared to persons with only 0 or 1 conditions, and for men (HR: 1.53, 95% CI, 1.01– 2.31) than for women (HR: 1.20, 95% CI, 0.83– 1.74). CONCLUSION In older adults, having multiple chronic conditions is associated with an increased risk of MCI/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 or dementia.

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IMPORTANCE Brain amyloid deposition is a marker of Alzheimer disease (AD) pathology. The population-based prevalence and outcomes of amyloid positivity in a population without dementia are important for understanding the trajectory of amyloid positivity to clinically significant outcomes and for designing AD prevention trials. OBJECTIVE To determine prevalence and outcomes of amyloid positivity in a population without dementia. DESIGN, SETTING, AND PARTICIPANTS In the prospective, population-based Mayo Clinic Study of Aging in Olmsted County, Minnesota, participants without dementia were randomly selected from the county population and were clinically and cognitively evaluated at baseline and every 15 months from August 1, 2008, to September 18, 2018. They were also invited to undergo carbon 11-Pittburgh compound B positron emission tomography (PET) imaging. EXPOSURES Amyloid positivity (defined as a standardized uptake value ratio >1.42 on PET). MAIN OUTCOMES AND MEASURES Prevalence of amyloid positivity in the Olmsted County population without dementia and risk of progression from no cognitive impairment (ie, normal cognition for age) to incident amnestic MCI (aMCI) and from MCI or aMCI to incident AD dementia. RESULTS Of 3894 participants, 1671 underwent PET imaging and were included in the study; 2198 did not undergo imaging, and 25 were excluded for other reasons. The mean (SD) age of participants was 71.3 (9.8) years; 892 (53.4%) were men, and 179 (10.7%) had prevalent MCI. The prevalence of amyloid positivity without cognitive impairment in the population without dementia increased from 2.7% (95% CI, 0.5% to 4.9%) in persons aged 50 to 59 years to 41.3% (95% CI, 33.4% to 49.2%) in those aged 80 to 89 years at baseline. Prevalence of amyloid-positive MCI in the population without dementia increased from 0% in persons aged 50 to 59 years to 16.4% (95% CI, 10.3% to 22.5%) in those aged 80 to 89 years. The incident aMCI risk increased more than 2-fold in participants without cognitive impairment who were amyloid positive vs those who were amyloid negative (hazard ratio [HR], 2.26; 95% CI, 1.52 to 3.35; P < .001). The risk of AD dementia was 1.86 (95% CI, 0.89 to 3.88; P = .10) for amyloid-positive participants with MCI vs amyloid-negative participants with MCI, 1.63 (95% CI, 0.78 to 3.41; P = .20) for participants with aMCI who were amyloid positive vs amyloid negative, and 2.56 (95% CI, 1.35 to 4.88; P = .004) for amyloid-positive participants who were either without cognitive impairment or had aMCI vs those who were amyloid negative. Global cognitive and memory domain z scores declined significantly in amyloid-positive individuals during follow-up. The mean (SD) follow-up time from baseline was 3.7 (1.9) years to incident aMCI and 3.8 (2.0) years to incident AD dementia. CONCLUSIONS AND RELEVANCE Population-based prevalence of amyloid-positive status and progression rates of amyloid positivity provide valid information for designing AD prevention trials and assessing the public health outcomes of AD preventi...

Objective: To determine the risk factors associated with dementia with Lewy bodies (DLB). Methods:We identified 147 subjects with DLB and sampled 2 sex-and age-matched cognitively normal control subjects for each case. We also identified an unmatched comparison group of 236 subjects with Alzheimer disease (AD). We evaluated 19 candidate risk factors in the study cohort.Results: Compared with controls, subjects with DLB were more likely to have a history of anxiety (odds ratio; 95% confidence interval) (7.4; 3.5-16; p , 0.0001), depression (6.0; 3.7-9.5; p , 0.0001), stroke (2.8; 1.3-6.3; p 5 0.01), a family history of Parkinson disease (PD) (4.6; 2.5-8.6; p , 0.0001), and carry APOE e4 alleles (2.2; 1.5-3.3; p , 0.0001), but less likely to have had cancer (0.44; 0.27-0.70; p 5 0.0006) or use caffeine (0.29; 0.14-0.57; p , 0.0001) with a similar trend for alcohol (0.65; 0.42-1.0; p 5 0.0501). Compared with subjects with AD, subjects with DLB were younger (72.5 vs 74.9 years, p 5 0.021) and more likely to be male (odds ratio; 95% confidence interval) (5.3; 3.3-8.5; p , 0.0001), have a history of depression (4.3; 2.4-7.5; p , 0.0001), be more educated (2.5; 1.1-5.6; p 5 0.031), have a positive family history of PD (5.0; 2.4-10; p , 0.0001), have no APOE e4 alleles (0.61; 0.40-0.93; p 5 0.02), and to have had an oophorectomy before age 45 years (7.6; 1.5-39; p 5 0.015).Conclusion: DLB risk factors are an amalgam of those for AD and PD. Smoking and education, which have opposing risk effects on AD and PD, are not risk factors for DLB; however, depression and low caffeine intake, both risk factors for AD and PD, increase risk of DLB more strongly than in either. Neurology Dementia with Lewy bodies (DLB) is the second most common dementia syndrome, representing 10% to 15% of cases. Knowledge of risk factors for DLB may provide clues to the underlying pathophysiology, yet the only known risk factors are advanced age, male sex, 1 and a family history of dementia.2 We compared the frequency of Alzheimer disease (AD) and Parkinson disease (PD) risk factors among subjects with DLB to age-and sex-matched controls, and to subjects with AD. Risk factors driving amyloid pathology should be present in AD and, to a lesser extent, in DLB. In contrast, risk factors driving Lewy body pathology should be found in DLB, but not AD or control subjects.METHODS Standard protocol approvals, registrations, and patient consents. All protocols were approved by our institutional review board, and consent was obtained from subjects and carers.Subjects. Subjects were recruited into 3 longitudinal studies at Mayo Clinic, Rochester, MN. The Alzheimer Disease Patient Registry (1985)(1986)(1987)(1988)(1989)(1990)(1991)(1992)(1993)(1994)(1995)(1996)(1997)(1998)(1999)(2000)(2001)(2002)(2003)(2004) 3 and Alzheimer Disease Research Center Study (1999-present) recruited patients with incident dementia and age-and sex-matched controls. The Mayo Clinic Study of Aging (2004-present) follows all community-dwelling persons aged 70 to 89 years.

INTRODUCTION The Mediterranean diet (MeDi) is associated with reduced risk of cognitive impairment, but it’s unclear whether it’s associated with better brain imaging biomarkers. METHODS Among 672 cognitively normal participants (mean age: 79.8 years, 52.5% men), we investigated associations of MeDi score and MeDi components with magnetic resonance imaging measures of cortical thickness for the 4 lobes separately and averaged (average lobar). RESULTS Higher MeDi score was associated with larger frontal, parietal, occipital, and average lobar cortical thickness. Higher legume and fish intakes were associated with larger cortical thickness: legumes with larger superior parietal, inferior parietal, precuneus, parietal, occipital, lingual, and fish with larger precuneus, superior parietal, posterior cingulate, parietal, inferior parietal. Higher carbohydrate and sugar intakes were associated with lower entorhinal cortical thickness. DISCUSSION In this sample of elderly persons, higher adherence to MeDi was associated with larger cortical thickness. These cross-sectional findings require validation in prospective studies.

Young patients present at a later stage and a greater proportion develop distant disease recurrence over time. However, their stage-specific oncologic outcomes appear similar to those in older-onset patients. To have the greatest impact on long-term oncologic outcomes in patients with young-onset rectal cancer, future interventions should target strategies to diagnosis rectal cancer earlier, and once diagnosed, closer surveillance for recurrence may be warranted.