Walter A Rocca

St. Anne´s University Hospital, Brünn, South Moravian, Czech Republic

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Publications (311)2020.49 Total impact

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    ABSTRACT: Importance: The role of amyloid in the progression of Alzheimer disease (AD) pathophysiology is of central interest to the design of randomized clinical trials. The presence of amyloid has become a prerequisite for enrollment in several secondary prevention trials for AD, yet the precise effect of elevated amyloid levels on subsequent clinical and biomarker events is less certain. Objective: To explore the effect of elevated amyloid levels on subsequent changes in cognition and biomarkers. Design, setting, and participants: A total of 564 cognitively normal individuals (median age, 78 years) from the Mayo Clinic Study of Aging, a population-based longitudinal study in Olmsted County, Minnesota, with serial cognitive data were selected for this study. The data used in this study were collected from January 12, 2006, to January 9, 2014. Individuals included in this study had undergone magnetic resonance imaging, fluorodeoxyglucose positron emission tomography (FDG-PET), and Pittsburgh Compound B (PiB) PET at baseline were not cognitively impaired at baseline and had at least 1 clinical follow-up. A subset of 286 individuals also underwent serial imaging. Elevated amyloid level was defined as a standardized uptake value ratio of greater than 1.5 on PiB PET. Associations with baseline amyloid status and baseline and longitudinal change in clinical and imaging measures were evaluated after adjusting for age and hippocampal volume. APOE4 effects were also evaluated. Main outcomes and measures: Cognitive measures of memory, language, attention/executive function, visuospatial skills, PiB levels, hippocampal and ventricular volumes, and FDG-PET measures. Results: At baseline, 179 (31.7%) individuals with elevated amyloid levels had poorer cognition in all domains measured, reduced hippocampal volume, and greater FDG-PET hypometabolism. Elevated amyloid levels at baseline were associated with a greater rate of cognitive decline in all domains (0.04 to 0.09 z score units per year) except language and a greater rate of amyloid accumulation (1.6% per year), hippocampal atrophy (30 mm3 per year), and ventricular enlargement (565 mm3 per year). Elevated amyloid levels were also associated with an increased risk of mild cognitive impairment (hazard ratio, 2.9; 95% CI, 1.7-5.0, and hazard ratio, 1.6; 95% CI, 0.9-2.8, for PiB+ APOE4 carriers and PiB+ noncarriers, respectively, compared with PiB- noncarriers). These associations were largely independent of APOE4. Conclusions and relevance: In persons selected from a population-based study, elevated amyloid levels at baseline were associated with worse cognition and imaging biomarkers at baseline and with greater clinical decline and neurodegeneration. These results have implications for the design of randomized clinical trials for AD.
    11/2015; DOI:10.1001/jamaneurol.2015.3098
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    ABSTRACT: Background: In a 2014 cross-sectional analysis, we showed that amyloid and neurodegeneration biomarker states in participants with no clinical impairment varied greatly with age, suggesting dynamic within-person processes. In this longitudinal study, we aimed to estimate rates of transition from a less to a more abnormal biomarker state by age in individuals without dementia, as well as to assess rates of transition to dementia from an abnormal state. Methods: Participants from the Mayo Clinic Study of Aging (Olmsted County, MN, USA) without dementia at baseline were included in this study, a subset of whom agreed to multimodality imaging. Amyloid PET (with (11)C-Pittsburgh compound B) was used to classify individuals as amyloid positive (A(+)) or negative (A(-)). (18)F-fluorodeoxyglucose ((18)F-FDG)-PET and MRI were used to classify individuals as neurodegeneration positive (N(+)) or negative (N(-)). We used all observations, including those from participants who did not have imaging results, to construct a multistate Markov model to estimate four different age-specific biomarker state transition rates: A(-)N(-) to A(+)N(-); A(-)N(-) to A(-)N(+) (suspected non-Alzheimer's pathology); A(+)N(-) to A(+)N(+); and A(-)N(+) to A(+)N(+). We also estimated two age-specific rates to dementia: A(+)N(+) to dementia and A(-)N(+) to dementia. Using these state-to-state transition rates, we estimated biomarker state frequencies by age. Findings: At baseline (between Nov 29, 2004, to March 7, 2015), 4049 participants did not have dementia (3512 [87%] were clinically normal and 537 [13%] had mild cognitive impairment). 1541 individuals underwent imaging between March 28, 2006, to April 30, 2015. Transition rates were low at age 50 years and, with one exception, exponentially increased with age. At age 85 years compared with age 65 years, the rate was nearly 11-times higher (17·2 vs 1·6 per 100 person-years) for the transition from A(-)N(-) to A(-)N(+), three-times higher (20·8 vs 6·1) for A(+)N(-) to A(+)N(+), and five-times higher (13·2 vs 2·6) for A(-)N(+) to A(+)N(+). The rate of transition was also increased at age 85 years compared with age 65 years for A(+)N(+) to dementia (7·0 vs 0·8) and for A(-)N(+) to dementia (1·7 vs 0·6). The one exception to an exponential increase with age was the transition rate from A(-)N(-) to A(+)N(-), which increased from 4·0 transitions per 100 person-years at age 65 years to 6·9 transitions per 100 person-years at age 75 and then plateaued beyond that age. Estimated biomarker frequencies by age from the multistate model were similar to cross-sectional biomarker frequencies. Interpretation: Our transition rates suggest that brain ageing is a nearly inevitable acceleration toward worse biomarker and clinical states. The one exception is the transition to amyloidosis without neurodegeneration, which is most dynamic from age 60 years to 70 years and then plateaus beyond that age. We found that simple transition rates can explain complex, highly interdependent biomarker state frequencies in our population. Funding: National Institute on Aging, Alexander Family Professorship of Alzheimer's Disease Research, the GHR Foundation.
    The Lancet Neurology 11/2015; DOI:10.1016/S1474-4422(15)00323-3 · 21.90 Impact Factor

  • Journal of Minimally Invasive Gynecology 11/2015; 22(6):S65. DOI:10.1016/j.jmig.2015.08.173 · 1.83 Impact Factor
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    ABSTRACT: 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.
    Neurology 10/2015; 85(19). DOI:10.1212/WNL.0000000000002100 · 8.29 Impact Factor
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    Virginia M Miller · Walter A Rocca · Stephanie S Faubion ·
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    ABSTRACT: The National Institutes of Health's (NIH) commitment to improving health outcomes for women and men through rigorous science has been compromised by the lack of basic science evidence obtained from female animals. To correct this limitation, in June 2015 the NIH announced expectations that "sex," as a biological variable, be included into research design and analysis in studies of vertebrate animals and humans (NOT-OD-15-102). Scientists must take the responsibility to implement this directive. However, in doing so, there is a risk that attention could be restricted to only studies of direct comparison between female/women and male/men. By contrast, understanding how sex influences health and disease needs to take a programmatic approach that includes the study of sex-specific conditions. A programmatic approach will assure the advancement of knowledge to improve women's health.
    Journal of Women's Health 09/2015; DOI:10.1089/jwh.2015.5498 · 2.05 Impact Factor
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    ABSTRACT: This study aims to determine the association of preexisting cardiovascular risk factors and cardiovascular diseases with hysterectomy with bilateral ovarian conservation using a case-central design. Using the Rochester Epidemiology Project records-linkage system, we identified all Olmsted County, MN women who underwent hysterectomy with ovarian conservation between January 1, 1965 and December 31, 2002 (cases). Each case was age-matched (±1 y) with a randomly selected woman who resided in the county and did not undergo hysterectomy or oophorectomy before the index date (date of hysterectomy in her matched case). Using electronic codes, we identified cardiovascular risk factors (diabetes, hypertension, hyperlipidemia, obesity, metabolic syndrome, and polycystic ovary syndrome) and cardiovascular diseases (coronary artery disease, congestive heart failure, myocardial infarction, and stroke) that occurred before the index date. Analyses were stratified by age at hysterectomy and indication for surgical operation. During the study period, 3,816 women underwent hysterectomy with ovarian conservation for a benign indication. Preexisting hyperlipidemia, obesity, and metabolic syndrome were significantly more frequent in cases than in controls in univariable analyses. In multivariable analyses, obesity remained significantly associated overall, for nearly all age groups, and across all indications. Stroke was significantly more frequent in cases than in controls among women younger than 36 years. Congestive heart failure and stroke were significantly less common in cases than in controls among women older than 50 years. Hysterectomy with ovarian conservation is associated with cardiovascular risk factors, particularly obesity. Obesity may contribute to underlying gynecologic conditions leading to hysterectomy; however, surgical selection may also play a role.
    Menopause (New York, N.Y.) 07/2015; DOI:10.1097/GME.0000000000000506 · 3.36 Impact Factor
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    S S Faubion · C L Kuhle · L T Shuster · W A Rocca ·
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    ABSTRACT: Aim: To review the current evidence concerning the long-term harmful effects of premature or early menopause, and to discuss some of the clinical implications. Material and methods: Narrative review of the literature. Results: Women undergoing premature or early menopause, either following bilateral salpingo-oophorectomy or because of primary ovarian insufficiency, experience the early loss of estrogen and other ovarian hormones. The long-term consequences of premature or early menopause include adverse effects on cognition, mood, cardiovascular, bone, and sexual health, as well as an increased risk of early mortality. The use of hormone therapy has been shown to lessen some, although not all of these risks. Therefore, multiple medical societies recommend providing hormone therapy at least until the natural age of menopause. It is important to individualize hormone therapy for women with early estrogen deficiency, and higher dosages may be needed to approximate physiological concentrations found in premenopausal women. It is also important to address the psychological impact of early menopause and to review the options for fertility and the potential need for contraception, if the ovaries are intact. Conclusions: Women who undergo premature or early menopause should receive individualized hormone therapy and counseling.
    Climacteric 04/2015; 18(4):1-9. DOI:10.3109/13697137.2015.1020484 · 2.26 Impact Factor
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    ABSTRACT: We sought to develop risk scores for the progression from cognitively normal (CN) to mild cognitive impairment (MCI). We recruited into a longitudinal cohort study a randomly selected, population-based sample of Olmsted County, MN, residents, aged 70 to 89 years on October 1, 2004. At baseline and subsequent visits, participants were evaluated for demographic, clinical, and neuropsychological measures, and were classified as CN, MCI, or dementia. Using baseline demographic and clinical variables in proportional hazards models, we derived scores that predicted the risk of progressing from CN to MCI. We evaluated the ability of these risk scores to classify participants for MCI risk. Of 1,449 CN participants, 401 (27.7%) developed MCI. A basic model had a C statistic of 0.60 (0.58 for women, 0.62 for men); an augmented model resulted in a C statistic of 0.70 (0.69 for women, 0.71 for men). Both men and women in the highest vs lowest sex-specific quartiles of the augmented model's risk scores had an approximately 7-fold higher risk of developing MCI. Adding APOE ε4 carrier status improved the model (p = 0.002). We have developed MCI risk scores using variables easily assessable in the clinical setting and that may be useful in routine patient care. Because of variability among populations, validation in independent samples is required. These models may be useful in identifying patients who might benefit from more expensive or invasive diagnostic testing, and can inform clinical trial design. Inclusion of biomarkers or other risk factors may further enhance the models. © 2015 American Academy of Neurology.
    Neurology 03/2015; 84(14). DOI:10.1212/WNL.0000000000001437 · 8.29 Impact Factor
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    ABSTRACT: Typical cognitive aging may be defined as age-associated changes in cognitive performance in individuals who remain free of dementia. Ideally, the full adult age spectrum should be included to assess brain imaging findings associated with typical aging. To compare age, sex, and APOE ε4 effects on memory, brain structure (adjusted hippocampal volume [HVa]), and amyloid positron emission tomography (PET) in cognitively normal individuals aged 30 to 95 years old. Cross-sectional observational study (March 2006 to October 2014) at an academic medical center. We studied 1246 cognitively normal individuals, including 1209 participants aged 50 to 95 years old enrolled in a population-based study of cognitive aging and 37 self-selected volunteers aged 30 to 49 years old. Memory, HVa, and amyloid PET. Overall, memory worsened from age 30 years through the 90s. The HVa worsened gradually from age 30 years to the mid-60s and more steeply beyond that age. The median amyloid PET was low until age 70 years and increased thereafter. Memory was worse in men than in women overall (P < .001) and more specifically beyond age 40 years. The HVa was lower in men than in women overall (P < .001) and more specifically beyond age 60 years. There was no sex difference in amyloid PET at any age. Within each sex, memory performance and HVa were not different by APOE ε4 status at any age. From age 70 years onward, APOE ε4 carriers had significantly greater median amyloid PET than noncarriers. However, the ages at which 10% of the population were amyloid PET positive were 57 years for APOE ε4 carriers and 64 years for noncarriers. Male sex is associated with worse memory and HVa among cognitively normal individuals, while APOE ε4 is not. In contrast, APOE ε4 is associated with greater amyloid PET (from age 70 years onward), while sex is not. Worsening memory and HVa occur at earlier ages than abnormal amyloid PET. Therefore, neuropathological processes other than β-amyloidosis must underlie declines in brain structure and memory function in middle age. Our findings are consistent with a model of late-onset Alzheimer disease in which β-amyloidosis arises in later life on a background of preexisting structural and cognitive decline that is associated with aging and not with β-amyloid deposits.
    JAMA Neurology 03/2015; 72(5). DOI:10.1001/jamaneurol.2014.4821 · 7.42 Impact Factor
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    ABSTRACT: To study the incidence of de novo multimorbidity across all ages in a geographically defined population with an emphasis on sex and ethnic differences. Historical cohort study. All persons residing in Olmsted County, Minnesota, USA on 1 January 2000 who had granted permission for their records to be used for research (n=123 716). We used the Rochester Epidemiology Project medical records-linkage system to identify all of the county residents. We identified and removed from the cohort all persons who had developed multimorbidity before 1 January 2000 (baseline date), and we followed the cohort over 14 years (1 January 2000 through 31 December 2013). Incident multimorbidity was defined as the development of the second of 2 conditions (dyads) from among the 20 chronic conditions selected by the US Department of Health and Human Services. We also studied the incidence of the third of 3 conditions (triads) from among the 20 chronic conditions. The incidence of multimorbidity increased steeply with older age; however, the number of people with incident multimorbidity was substantially greater in people younger than 65 years compared to people age 65 years or older (28 378 vs 6214). The overall risk was similar in men and women; however, the combinations of conditions (dyads and triads) differed extensively by age and by sex. Compared to Whites, the incidence of multimorbidity was higher in Blacks and lower in Asians. The risk of developing de novo multimorbidity increases steeply with older age, varies by ethnicity and is similar in men and women overall. However, as expected, the combinations of conditions vary extensively by age and sex. These data represent an important first step toward identifying the causes and the consequences of multimorbidity. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to
    BMJ Open 02/2015; 5(2):e006413. DOI:10.1136/bmjopen-2014-006413 · 2.27 Impact Factor
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    ABSTRACT: Our primary objective was to investigate a biomarker driven model for the interrelationships between vascular disease pathology, amyloid pathology, and longitudinal cognitive decline in cognitively normal elderly subjects between 70 and 90 years of age. Our secondary objective was to investigate the beneficial effect of cognitive reserve on these interrelationships. We used brain amyloid-β load measured using Pittsburgh compound B positron emission tomography as a marker for amyloid pathology. White matter hyperintensities and brain infarcts were measured using fluid-attenuated inversion recovery magnetic resonance imaging as a marker for vascular pathology. We studied 393 cognitively normal elderly participants in the population-based Mayo Clinic Study of Aging who had a baseline 3 T fluid-attenuated inversion recovery magnetic resonance imaging assessment, Pittsburgh compound B positron emission tomography scan, baseline cognitive assessment, lifestyle measures, and at least one additional clinical follow-up. We classified subjects as being on the amyloid pathway if they had a global cortical amyloid-β load of ≥1.5 standard uptake value ratio and those on the vascular pathway if they had a brain infarct and/or white matter hyperintensities load ≥1.11% of total intracranial volume (which corresponds to the top 25% of white matter hyperintensities in an independent non-demented sample). We used a global cognitive z-score as a measure of cognition. We found no evidence that the presence or absence of vascular pathology influenced the presence or absence of amyloid pathology and vice versa, suggesting that the two processes seem to be independent. Baseline cognitive performance was lower in older individuals, in males, those with lower education/occupation, and those on the amyloid pathway. The rate of cognitive decline was higher in older individuals (P < 0.001) and those with amyloid (P = 0.0003) or vascular (P = 0.0037) pathologies. In those subjects with both vascular and amyloid pathologies, the effect of both pathologies on cognition was additive and not synergistic. For a 79-year-old subject, the predicted annual rate of global z-score decline was -0.02 if on neither pathway, -0.07 if on the vascular pathway, -0.08 if on the amyloid pathway and -0.13 if on both pathways. The main conclusions of this study were: (i) amyloid and vascular pathologies seem to be at least partly independent processes that both affect longitudinal cognitive trajectories adversely and are major drivers of cognitive decline in the elderly; and (ii) cognitive reserve seems to offset the deleterious effect of both pathologies on the cognitive trajectories. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain.
    Brain 01/2015; 138(3). DOI:10.1093/brain/awu393 · 9.20 Impact Factor
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    ABSTRACT: Inexpensive, non-invasive tools for assessing Alzheimer-type pathophysiologies are needed. Computerized cognitive assessments are prime candidates. Cognitively normal participants, aged 51-71, with magnetic resonance imaging, fluorodeoxyglucose-positron emission tomography (FDG-PET), amyloid PET, CogState computerized cognitive assessment, and standard neuropsychological tests were included. We first examined the association between the CogState battery and neuroimaging measures. We then compared that association to the one between standard neuropsychological z-scores and neuroimaging. Slower reaction times for CogState Identification and One Back, and lower memory and attention z-scores, were associated (P < .05) with FDG-PET hypometabolism. Slower time on the Groton Maze Learning Task and worse One Card Learning accuracy were associated (P < .05) with smaller hippocampal volumes. There were no associations with amyloid PET. Associations of CogState and neuropsychological Z-scores with neuroimaging were small and of a similar magnitude. CogState subtests were cross-sectionally comparable to standard neuropsychological tests in their relatively weak associations with neurodegeneration imaging markers. Copyright © 2014 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
    Alzheimer's & dementia: the journal of the Alzheimer's Association 11/2014; 10(6):779-89. DOI:10.1016/j.jalz.2014.09.001 · 12.41 Impact Factor
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    ABSTRACT: This is a narrative review of new ideas and concepts related to differences between men and women in their risk of developing dementia or Alzheimer's disease (AD). We introduce the concept of dimorphic neurology and the distinction between sex and gender. We then provide three examples of risk factors related to sex and gender from the literature. Apolipoprotein E genotype is equally common in men and women but has a stronger effect in women. Apolipoprotein E genotype is a biological factor that cannot be modified but interacts with sex or gender related factors that can be modified. Low education has a similar harmful effect in men and women but has been historically more common in women. Education is a social factor related to gender that can be modified. Finally, bilateral oophorectomy is a factor restricted to women. Bilateral oophorectomy is a surgical practice related to sex that can be modified. Consideration of risk and protective factors in men and women separately may accelerate etiologic research for neurological diseases in general, and for dementia and AD in particular. Similarly, future preventive interventions for dementia should be tailored to men and women separately.
    Maturitas 10/2014; 79(2). DOI:10.1016/j.maturitas.2014.05.008 · 2.94 Impact Factor

  • Journal of Women's Health 10/2014; 23(10):863-863. · 2.05 Impact Factor
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    ABSTRACT: Background As preclinical Alzheimer's disease becomes a target for therapeutic intervention, the overlap between imaging abnormalities associated with typical ageing and those associated with Alzheimer's disease needs to be recognised. We aimed to characterise how typical ageing and preclinical Alzheimer's disease overlap in terms of β-amyloidosis and neurodegeneration. Methods We measured age-specific frequencies of amyloidosis and neurodegeneration in individuals with normal cognitive function aged 50–89 years. Potential participants were randomly selected from the Olmsted County (MN, USA) population-based study of cognitive ageing and invited to participate in cognitive and imaging assessments. To be eligible for inclusion, individuals must have been judged clinically to have no cognitive impairment and have undergone amyloid PET, 18F-fluorodeoxyglucose (18F-FDG) PET, and MRI. Imaging results were obtained from March 28, 2006, to Dec 3, 2013. Amyloid status (positive [A+] or negative [A–]) was determined by amyloid PET with 11C Pittsburgh compound B. Neurodegeneration status (positive [N+] or negative [N–]) was determined by an Alzheimer's disease signature 18F-FDG PET or hippocampal volume on MRI. We determined age-specific frequencies of the four groups (amyloid negative and neurodegeneration negative [A–N–], amyloid positive and neurodegeneration negative [A+N–], amyloid negative and neurodegeneration positive [A–N+], or amyloid positive and neurodegeneration positive [A+N+]) cross-sectionally using multinomial regression models. We also investigated associations of group frequencies with APOE ɛ4 status (assessed with DNA extracted from blood) and sex by including these covariates in the multinomial models. Findings The study population consisted of 985 eligible participants. The population frequency of A–N– was 100% (n=985) at age 50 years and fell to 17% (95% CI 11–24) by age 89 years. The frequency of A+N– increased to 28% (24–32) at age 74 years, then decreased to 17% (11–25) by age 89 years. The frequency of A–N+ increased from age 60 years, reaching 24% (16–34) by age 89 years. The frequency of A+N+ increased from age 65 years, reaching 42% (31–52) by age 89 years. The results from our multinomial models suggest that A+N– and A+N+ were more frequent in APOE ɛ4 carriers than in non-carriers and that A+N+ was more, and A+N– less frequent in men than in women. Interpretation Accumulation of amyloid and neurodegeneration are nearly inevitable by old age, but many people are able to maintain normal cognitive function despite these imaging abnormalities. Changes in the frequency of amyloidosis and neurodegeneration with age, which seem to be modified by APOE ɛ4 and sex, suggest that pathophysiological sequences might differ between individuals. Funding US National Institute on Aging and Alexander Family Professorship of Alzheimer's Disease Research.
    The Lancet Neurology 10/2014; 13(10). DOI:10.1016/S1474-4422(14)70194-2 · 21.90 Impact Factor
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    ABSTRACT: Background: Comorbidities are a major concern in heart failure, leading to adverse outcomes, increased health care utilization, and excess mortality. Nevertheless, the epidemiology of comorbid conditions and differences in their occurrence by type of heart failure and sex are not well documented. Methods: The prevalence of 16 chronic conditions defined by the US Department of Health and Human Services was obtained among 1382 patients from Olmsted County, Minn. diagnosed with first-ever heart failure between 2000 and 2010. Heat maps displayed the pairwise prevalences of the comorbidities and the observed-to-expected ratios for occurrence of morbidity pairs by type of heart failure (preserved or reduced ejection fraction) and sex. Results: Most heart failure patients had 2 or more additional chronic conditions (86%); the most prevalent were hypertension, hyperlipidemia, and arrhythmias. The co-occurrence of other cardiovascular diseases was common, with higher prevalences of co-occurring cardiovascular diseases in men compared with women. Patients with preserved ejection fraction had one additional condition compared with those with reduced ejection fraction (mean 4.5 vs 3.7). The patterns of co-occurring conditions were similar between preserved and reduced ejection fraction; however, differences in the ratios of observed-to-expected co-occurrence were apparent by type of heart failure and sex. In addition, some psychological and neurological conditions co-occurred more frequently than expected. Conclusion: Multimorbidity is common in heart failure, and differences in co-occurrence of conditions exist by type of heart failure and sex, highlighting the need for a better understanding of the clinical consequences of multiple chronic conditions in heart failure patients.
    The American Journal of Medicine 09/2014; 128(1). DOI:10.1016/j.amjmed.2014.08.024 · 5.00 Impact Factor
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    ABSTRACT: Objective: To describe the prevalence of multimorbidity involving 20 selected chronic conditions in a geographically defined US population, emphasizing age, sex, and racial/ethnic differences. Patients and methods: Using the Rochester Epidemiology Project records linkage system, we identified all residents of Olmsted County, Minnesota, on April 1, 2010, and electronically extracted the International Classification of Diseases, Ninth Revision codes associated with all health care visits made between April 1, 2005, and March 31, 2010 (5-year capture frame). Using these codes, we defined the 20 common chronic conditions recommended by the US Department of Health and Human Services. We counted only persons who received at least 2 codes for a given condition separated by more than 30 days, and we calculated the age-, sex-, and race/ethnicity-specific prevalence of multimorbidity. Results: Of the 138,858 study participants, 52.4% were women (n=72,732) and 38.9% had 1 or more conditions (n=54,012), 22.6% had 2 or more conditions (n=31,444), and 4.9% had 5 or more conditions (n=6853). The prevalence of multimorbidity (≥2 conditions) increased steeply with older age and reached 77.3% at 65 years and older. However, the absolute number of people affected by multimorbidity was higher in those younger than 65 years. Although the prevalence of multimorbidity was similar in men and women overall, the most common dyads and triads of conditions varied by sex. Compared with white persons, the prevalence of multimorbidity was slightly higher in black persons and slightly lower in Asian persons. Conclusion: Multimorbidity is common in the general population; it increases steeply with older age, has different patterns in men and women, and varies by race/ethnicity.
    Mayo Clinic Proceedings 09/2014; 89(10). DOI:10.1016/j.mayocp.2014.07.010 · 6.26 Impact Factor
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    ABSTRACT: The aim of this work was to study time trends of antidepressant drug (AD) prescriptions in a geographically defined US population between 2005 and 2011 for men and women separately. Using the Rochester Epidemiology Project medical records-linkage system, we identified all Olmsted County, MN residents who received AD outpatient prescriptions between 2005 and 2011 (7 years). We calculated the annual age- and sex-specific prevalence over 7 years and used generalized estimating equation models to test for time trends. The prevalence of subjects receiving at least one AD prescription was approximately two times higher in women than in men consistently across the 7 years of the study. The standardized annual prevalence increased from 10.8 % in 2005 to 14.4 % in 2011 overall, from 7.0 % in 2005 to 9.9 % in 2011 for men, and from 14.4 % in 2005 to 18.6 % in 2011 for women. The absolute percent increase was greater in women (4.2 vs. 2.9 %; standardized); however, the relative percent increase was greater in men (41.4 vs. 29.2 %; standardized). The relative percent increase was greater in the age group 65+ years for both men and women. AD prescriptions are increasing over time, especially in the elderly. Women receive more AD prescriptions than men. However, the relative increase in AD prescriptions over time is greater in men than women.
    Archives of Women s Mental Health 08/2014; 17(6). DOI:10.1007/s00737-014-0450-7 · 2.16 Impact Factor
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    ABSTRACT: To determine the extent to which excess mortality following fractures due to particular causes at specific skeletal sites can be predicted using data about all medical diagnoses, we conducted an historical cohort study among 1991 Olmsted County, Minnesota residents ≥50 years of age who experienced any fracture in 1989-1991 and who were followed passively for up to 22 years for death from any cause. We used a machine learning approach, gradient boosting machine (GBM) modeling, to determine whether the comorbid conditions present at the time of fracture and those that arose subsequently could, in aggregate, identify patients at the greatest increased risk of death. During 21,867 person-years of follow-up, 1245 deaths were observed when 1061 were expected (standardized mortality ratio, 1.2; 95% CI 1.1 to 1.2). Patients presented with a median history of 26 comorbid conditions each as assessed by the Clinical Classification Software system, and 57 each over the total duration of follow-up. Using all available information, the excess deaths could be predicted with good accuracy (c-index ≥0.80) in 89% of the GBM models built for patients with different types of fracture; in one-third of the models, the c-index was ≥0.90. The conditions most prominent in the GBM prediction models were also reflected in the specific causes of death that were elevated, suggesting the influence of confounding on the relationship. However, the predominant comorbid conditions were mainly those responsible for mortality in the general population, rather than the specific diseases most closely associated with secondary osteoporosis. To reduce long-term deaths in the fracture population as a whole, a more general approach to the fracture patient is indicated. © 2014 American Society for Bone and Mineral Research
    Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 07/2014; 29(7). DOI:10.1002/jbmr.2193 · 6.83 Impact Factor
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    Alzheimer's and Dementia 07/2014; 10(4):P228-P229. DOI:10.1016/j.jalz.2014.04.325 · 12.41 Impact Factor

Publication Stats

16k Citations
2,020.49 Total Impact Points


  • 2014
    • St. Anne´s University Hospital
      Brünn, South Moravian, Czech Republic
    • Mayo Foundation for Medical Education and Research
      Рочестер, Michigan, United States
  • 1994-2014
    • Mayo Clinic - Rochester
      • • Department of Neurology
      • • Department of Health Science Research
      Рочестер, Minnesota, United States
    • It-Robotics
      Vicenza, Veneto, Italy
  • 2011
    • Olmsted Medical Center
      Rochester, Minnesota, United States
  • 1999-2009
    • Università degli Studi di Messina
      • Dipartimento di Neuroscienze
      Messina, Sicily, Italy
    • Mayo Clinic - Scottsdale
      Scottsdale, Arizona, United States
  • 2000
    • University of Manitoba
      Winnipeg, Manitoba, Canada
  • 1997
    • Unité Inserm U1077
      Caen, Lower Normandy, France
  • 1996
    • Columbia University
      • College of Physicians and Surgeons
      New York, New York, United States
    • University of Naples Federico II
      Napoli, Campania, Italy
  • 1995-1996
    • University of Texas Health Science Center at Houston
      • School of Public Health
      Houston, Texas, United States
  • 1989-1994
    • University of Florence
      • Dipartimento di Neuroscienze, Psicologia, Area del Farmaco e Salute del Bambino
      Florens, Tuscany, Italy
  • 1992
    • Università degli Studi di Palermo
      • Department of experimental medicine and clinical neurosciences
      Palermo, Sicily, Italy
  • 1991
    • Australian National University
      Canberra, Australian Capital Territory, Australia
    • University of Maryland, Baltimore
      • Department of Psychiatry
      Baltimore, MD, United States
    • University of Ferrara
      • Sezione di Neurologia
      Ferrare, Emilia-Romagna, Italy
  • 1988
    • Università degli Studi di Torino
      Torino, Piedmont, Italy
  • 1986-1987
    • National Institutes of Health
      • Branch of Epidemiology (EPI)
      Maryland, United States