Walter A Rocca

Mayo Clinic - Rochester, Рочестер, Minnesota, United States

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Publications (340)2066.4 Total impact

  • No preview · Article · Jan 2016 · American Journal of Obstetrics and Gynecology
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    ABSTRACT: Objectives: To estimate the risk of fatal and non-fatal myocardial infarction (MI) and stroke in patients with bipolar I disorder compared to people without bipolar I disorder. Method: Utilizing a records-linkage system spanning 30 years (1966-1996), a population-based cohort of 334 subjects with bipolar I disorder and 334 age and sex-matched referents from Olmsted County, Minnesota, U.S. was identified. Longitudinal follow-up continued until incident MI or stroke (confirmed by board-certified cardiologist/neurologist), death, or study end date (December 31, 2013). Cox proportional hazards models assessed the hazard ratio (HR) for MI or stroke, adjusting for potential confounders. Results: There was an increased risk of fatal or non-fatal MI or stroke (as a composite outcome) in patients with bipolar I disorder [HR 1.54, 95% confidence interval (CI) 1.02, 2.33; p=0.04]. However, after adjusting for baseline cardiovascular risk factors (alcoholism, hypertension, diabetes, and smoking), the risk was no longer significantly increased (HR 1.19, 95% CI 0.76, 1.86; p=0.46). Limitations: Small sample size for the study design. Findings were not retained after adjustment for cardiovascular disease risk factors. Psychotropic medication use during the follow-up was not ascertained and was not included in the analyses. Conclusion: This study in a geographically defined region in the U.S. demonstrated a significant increased risk of MI or stroke in bipolar I disorder, which was no longer significant after adjustment for cardiovascular risk factors.
    No preview · Article · Jan 2016 · Journal of Affective Disorders
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    Stephanie S Faubion · Julia A Files · Walter A Rocca

    Full-text · Article · Jan 2016 · Journal of Women's Health
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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.
    No preview · Article · Nov 2015
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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.
    No preview · Article · Nov 2015 · The Lancet Neurology

  • No preview · Article · Nov 2015 · Journal of Minimally Invasive Gynecology
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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.
    No preview · Article · Oct 2015 · Neurology
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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.
    Full-text · Article · Sep 2015 · Journal of Women's Health
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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.
    No preview · Article · Jul 2015 · Menopause (New York, N.Y.)

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  • Walter Rocca

    No preview · Article · Jul 2015
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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.
    Full-text · Article · Apr 2015 · Climacteric
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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.
    No preview · Article · Mar 2015 · Neurology
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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.
    No preview · Article · Mar 2015 · JAMA Neurology
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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
    Full-text · Article · Feb 2015 · BMJ Open
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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.
    Full-text · Article · Jan 2015 · Brain

Publication Stats

17k Citations
2,066.40 Total Impact Points


  • 1994-2015
    • Mayo Clinic - Rochester
      • • Department of Neurology
      • • Department of Health Science Research
      Рочестер, Minnesota, United States
  • 2014
    • Mayo Foundation for Medical Education and Research
      Рочестер, Michigan, United States
    • St. Ann's University Hospital Brno
      Brünn, South Moravian, Czech Republic
  • 2013
    • Stanford University
      Stanford, California, United States
  • 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
  • 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
    • University of Ferrara
      • Sezione di Neurologia
      Ferrare, Emilia-Romagna, Italy
    • Australian National University
      Canberra, Australian Capital Territory, Australia
  • 1988
    • Università degli Studi di Torino
      Torino, Piedmont, Italy
  • 1986-1987
    • National Institutes of Health
      • Branch of Epidemiology (EPI)
      Maryland, United States