- Email: [email protected]
P4-126: Metabolic syndrome, successful and pathological neuroaging in a stroke-free elderly population
T706 P4-124
Poster Presentations P4: IS DEMENTIA UNDERDIAGNOSED? A NATIONWIDE POPULATION-BASED STUDY USING NATIONAL REGISTERS
Kieu T. T. Phung1, Berit L. Waltoft2, Lars V. Kessing1, Preben B. Mortensen2, Gunhild Waldemar1, 1Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark; 2National Center for Register-Bases Research, Aarhus, Denmark. Contact e-mail: [email protected] Background: Today, dementia is believed to be significantly underdiagnosed and undertreated. To evaluate the extent to which dementia had been diagnosed in the secondary health-care sector, we conducted a nationwide longitudinal study of incidence and prevalence of dementia over 34 years using the Danish national registers. Methods: Linking the Danish Civil Registration System with the Danish hospital registers, the whole Danish population was followed from their 40th birthday or January 1, 1970, whichever came later, to date of dementia diagnoses registered for the first time in the hospital registers both as in- and outpatients, date of emigration, date of death, or December 31, 2004, whichever came first. Age-, gender-, and period-specific incidence rates and prevalence of dementia were calculated and compared to estimates from large community-based cohort studies in Europe. Results: The study population consisted of 4,723,838 persons with 81,090,583 person-years of follow-up. From 1970 to 2004, 154,152 dementia cases were identified. The average age at diagnosis was 78.5 (SD 9.8). Following the global phenomenon, incidence of dementia was very low before the age of 65 but started to double thereafter for every 5-year increment in age. Taking the 2003 as the year with the most complete registration, the age-standardized incidence rate for the population older than 65 in 2003 was 10.46 per 1000 person-years. Compared to the age-standardized incidence rate of 15.79 per 1000 person-years from large European community-based cohort studies, a standardized incidence rate ratio of 0.66 was obtained. Conclusions: A surprisingly high number of the expected dementia cases in the population, about two-thirds of them, were diagnosed in the secondary health-care sector. This finding challenges the belief that dementia is significantly underdiagnosed. Additionally, being able to capture two-thirds of the nationwide dementia cases, the Danish hospital registers prove to be valuable and valid resources for studies in dementia epidemiology.
P4-125
HYSTERECTOMY IN PREMENOPAUSAL WOMEN IS ASSOCIATED WITH INCREASED RISK FOR EARLY ONSET DEMENTIA: A NATIONWIDE REGISTER-BASED STUDY
Kieu T. T. Phung1, Thomas M. Laursen2, Annette Settnes3, Lars V. Kessing1, Preben B. Mortensen2, Gunhild Waldemar1, 1 Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark; 2National Center for Register-Bases Research, Aarhus, Denmark; 3Hillerød University Hospital, Copenhagen, Denmark. Contact e-mail: [email protected] Background: Globally, hysterectomy is a very common surgical procedure among women and approximately 80% of hysterectomies are done on benign indications to increase quality of life. Recent studies have indicated that hysterectomy could be associated with increased risk for dementia. To determine whether hysterectomy is a risk factor for dementia, we conducted a nationwide historical cohort study using the Danish national registers. Methods: From the Danish Civil Registration System, a cohort was selected consisting of all female Danish residents born before 1966 (at least 40 years old in 2006). By linking data with the Danish hospital registers, this cohort was followed from January 1st, 1977 or the age of 40, whichever came later, until date of dementia diagnosis registered for the first time in the hospital registers,
date of death, date of immigration, or December 31st, 2006, whichever came first. Women diagnosed with dementia before 1977 and women who have undergone oophorectomies were excluded. The relative risks for developing dementia were stratified by age at hysterectomies (2030, 30-40, 40-45, 45-49, 50-55, 55-59, 60-69, 70-79, 80-89, 90 and above). All the relative risks were controlled for age at dementia diagnosis (one-year strata) and calendar year (one-year strata) at dementia diagnosis. Results: The cohort consisted of 2,313,388 females with 37,186,116 person-years of follow-up. From 1977 to 2006, there were 95,257 dementia cases and 1,309 hysterectomies. Compared to referent women of the same age group who had never had hysterectomies, women who had undergone hysterectomies had an increased risk of dementia, but only with early-onset dementia (dementia onset between 40-50 years old) (1.37, CI: 1.06, 1.77). Within this group of early-onset dementia, the younger was the age at hysterectomy, the greater was the risk. Conclusions: Premenopausal hysterectomy was associated with early-onset dementia, regardless of ovarian status. The effect of hysterectomy on early-onset dementia was age-dependent. Further studies are needed to confirm this association and to clarify the mechanisms underlying this association. As hysterectomy is such a common operation among women worldwide, this is an area where risk modification may have a great public health impact. P4-126
METABOLIC SYNDROME, SUCCESSFUL AND PATHOLOGICAL NEUROAGING IN A STROKEFREE ELDERLY POPULATION
Matheus Roriz-Cruz1, Idiane Rosset1, Teiji Sakagami2, Jarbas S. Roriz-Filho3, Eliane P. Morais1, Rosalina A. P. Rodrigues3, Kozo Matsubayashi2, 1Federal University of Rio Grande do Sul State, Brazil, Porto Alegre, Brazil; 2Kyoto University, Kyoto, Japan; 3 University of Sa˜o Paulo, Sa˜o Paulo, Brazil. Contact e-mail: [email protected] Background: Large part of the age-related neurofunctional decline is associated with stroke and cerebral microangiopathy. Metabolic Syndrome (Met.S) is a risk factor for both of these cerebrovascular disorders. It is unknown if Met.S is associated with neurofunctional decline in a stroke-free population. Methods: We evaluated 422 healthy community-dwelling elderly (ⱖ 60) in Brazil. Mini-Mental State Examination (MMSE), Geriatric Depression Scale (GDS), ‘Up&Go’ and Functional Reach tests, Executive Function and Activities of Daily Living were assessed. All reported values have P ⬍ 0.05. Results: Met.S was present in 39.3% of the subjects. Neurofunctional scores were significantly lower in the Met.S than in the control group (F: 2.7-5.9). Age alone explained 47% of all MMSE variance in the Met.S group, but just 12.8% among controls (P ⬍ 0.001 for difference). Age accounted for 18.7% of the variance on GDS in the Met.S group, whereas GDS score was not related to age in the control group. Analogously, the control group tended to have a more homogeneous score through all ages for every variable, whereas the Met.S group tended to have lower performances with increasing age (P ⬍ 0.05 for all differences). Adjusting for individual Met.S components reduced the power of the correlations between the number of Met.S components and evaluated neurofunctional scores (from R: 0.130-0.227 to R: 0.101-0.183), but did not eliminate their statistical significances, evidencing a synergism. The strong inverse correlation between the MMSE and GDS scales was restricted to the Met.S group (B: 0.38; P ⱕ 0.001). Conclusions: Met.S was independently associated with lower cognitive, executive, neuromotor and functional scores, and with more depressive symptoms. Association between cognitive dysfunction and depressive symptoms were explained in terms of Met.S-associated cerebrovascular risk. Met.S might be a major determinant of ‘successful’ or ‘pathological’ neuroaging in western societies.
Poster Presentations P4:
T707
were investigated for their health status/habits at midlife and re-examination. Results: Persons who participated in leisure time physical activity at midlife tended to have larger total brain volume ( 0.12; 95% CI -0.171.16, p⫽0.10) later in life than the more sedentary persons even after adjustments for socio-demographic and vascular factors, apoE ⑀4 genotype, smoking, diagnosis of dementia or mild cognitive impairment and cerebrospinal fluid/white matter/grey matter volumes. Interestingly, GM volume was significantly larger among the active ( 0.19; 95% CI 0.071.48, p⫽0.03), whereas the association between midlife physical activity and larger WM volume became non-significant after full adjustments. Further, the differences in the GM density between the active and sedentary groups localized mainly in frontal lobes. Finally, there was no significant association between midlife physical activity and severe WML later in life after full adjustments. Conclusions: Midlife physical activity might have an effect on total brain and GM volumes later in life, while there might not be an association between midlife physical activity and either WM volume or WML later in life. However, more studies with different methods are warranted for further understanding about the association between physical activity and structural brain changes. P4-128
AGING-RELATED PRIMARY BRAIN ATROPHY: FREQUENCY, ASSOCIATION WITH DEMENTIA, AND RISK FACTORS IN THE HONOLULU-ASIA AGING STUDY
Lon R. White1,2, Helen Petrovitch1,2, Webster Ross3, Jane H. Ueyhara-Lock1,4, Kamal Masaki1,4, Aaron McMurtray4, SaJung Yun1, William Markesbery5, 1Pacific Health Research Institute, Honolulu, HI, USA; 2Kuakini Medical Center, Honolulu, HI, USA; 3 Honolulu Veteran’s Administration, Honolulu, HI, USA; 4University of Hawaii School of Medicine, Honolulu, HI, USA; 5University of Kentucky School of Medicine, Lexington, KY, USA. Contact e-mail: [email protected]
P4-127
THE EFFECT OF MIDLIFE PHYSICAL ACTIVITY ON SUBSEQUENT STRUCTURAL BRAIN CHANGES
Suvi Rovio1, Gabriela Spulber2, Lasse J. Nieminen2, Eini Niskanen2, Bengt Winblad1, Jaakko Tuomilehto3, Aulikki Nissinen3, Hilkka Soininen2, Miia Kivipelto1, 1Karolinska Institutet, Stockholm, Sweden; 2University of Kuopio, Kuopio, Finland; 3National Public Health Institute, Helsinki, Finland. Contact e-mail: [email protected] Background: Physical activity has been associated with decreased risk of dementia in recent studies. Simultaneously, several dementia risk factors have been associated with WML and/or brain atrophy in magnetic resonance images (MRI), but the role of physical activity is unclear. In this study, we aimed at clarifying the associations between midlife physical activity and subsequent structural brain changes using MRI. Methods: The CAIDE subjects were randomly selected from population based samples first studied in 1972-1987, and re-examined in 1998 (average follow-up time 21 years). For this study, a subpopulation of 91 persons was scanned at the re-examination with Siemens Magnetom 1.5T MR scanner, and T1-weighted images were used to investigate grey matter (GM) density using voxel-based morphometry. WML were assessed on FLAIR-images using a semi-quantitative visual rating scale. Additionally, all participants
Background: Brain atrophy at autopsy is often associated with Alzheimer lesions, microinfarcts or lacunes, cortical Lewy bodies, or hippocampal atrophy. When observed in elderly decedents in the absence of any of these or other specific lesions it is provisionally designated aging-related primary brain atrophy (ARPBA). Methods: To facilitate analyses of brain atrophy at autopsy we developed a composite index comparing brain mass and mantle thickness with imputed estimates of the same measures prior to onset of atrophy by reference to estimated intracranial volumes (contributing 50% and 40% to the composite index). A neuropathologist’s qualitative assessment of neuronal loss in 8 neocortical gray matter regions contributed an additional 10% to the index. Results: Moderate (n⫽18) or severe (n⫽8) ARPBR was identified in 14.5% of 181 HAAS research protocol brain autopsies in which none of the lesions mentioned were present at clinically significant levels. In these 181 decedents severity of atrophy was significantly (p⬍0.0001) associated with cognitive impairment or dementia in the final years of life, controlling for education, ApoE4, and levels (all negligible) of neocortical neurofibrillary tangles, neuritic plaques, microvascular infarcts, and Lewy bodies. Among decedents with mild or negligible atrophy, 8% had been demented (by DSMIII-R criteria) and another 26% had definite cognitive impairment. Among decedents with moderate ARPBA, 28% had been demented and an additional 22% were impaired. Among decedents with severe ARPBA, 25% had been demented while an additional 37.5% had been cognitively impaired. Most of the dementia cases had been attributed to Alzheimer’s disease during life. An extensive search for risk factors associated with atrophy severity in these 181 decedents identified only advanced age (p⫽0.008) and elevated midlife systolic blood pressure (p⫽0.002). Conclusions: The pathogenesis of ARPBA is not understood. Further investigation may identify histopathologic changes that will allow more precise diagnoses. Since one type of pathologic process rarely precludes others, it is likely that the atrophy observed in older decedents with Alzheimer lesions, microvascular ischemic lesions, hippocampal sclerosis, or cortical
Poster Presentations P4: IS DEMENTIA UNDERDIAGNOSED? A NATIONWIDE POPULATION-BASED STUDY USING NATIONAL REGISTERS
Kieu T. T. Phung1, Berit L. Waltoft2, Lars V. Kessing1, Preben B. Mortensen2, Gunhild Waldemar1, 1Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark; 2National Center for Register-Bases Research, Aarhus, Denmark. Contact e-mail: [email protected] Background: Today, dementia is believed to be significantly underdiagnosed and undertreated. To evaluate the extent to which dementia had been diagnosed in the secondary health-care sector, we conducted a nationwide longitudinal study of incidence and prevalence of dementia over 34 years using the Danish national registers. Methods: Linking the Danish Civil Registration System with the Danish hospital registers, the whole Danish population was followed from their 40th birthday or January 1, 1970, whichever came later, to date of dementia diagnoses registered for the first time in the hospital registers both as in- and outpatients, date of emigration, date of death, or December 31, 2004, whichever came first. Age-, gender-, and period-specific incidence rates and prevalence of dementia were calculated and compared to estimates from large community-based cohort studies in Europe. Results: The study population consisted of 4,723,838 persons with 81,090,583 person-years of follow-up. From 1970 to 2004, 154,152 dementia cases were identified. The average age at diagnosis was 78.5 (SD 9.8). Following the global phenomenon, incidence of dementia was very low before the age of 65 but started to double thereafter for every 5-year increment in age. Taking the 2003 as the year with the most complete registration, the age-standardized incidence rate for the population older than 65 in 2003 was 10.46 per 1000 person-years. Compared to the age-standardized incidence rate of 15.79 per 1000 person-years from large European community-based cohort studies, a standardized incidence rate ratio of 0.66 was obtained. Conclusions: A surprisingly high number of the expected dementia cases in the population, about two-thirds of them, were diagnosed in the secondary health-care sector. This finding challenges the belief that dementia is significantly underdiagnosed. Additionally, being able to capture two-thirds of the nationwide dementia cases, the Danish hospital registers prove to be valuable and valid resources for studies in dementia epidemiology.
P4-125
HYSTERECTOMY IN PREMENOPAUSAL WOMEN IS ASSOCIATED WITH INCREASED RISK FOR EARLY ONSET DEMENTIA: A NATIONWIDE REGISTER-BASED STUDY
Kieu T. T. Phung1, Thomas M. Laursen2, Annette Settnes3, Lars V. Kessing1, Preben B. Mortensen2, Gunhild Waldemar1, 1 Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark; 2National Center for Register-Bases Research, Aarhus, Denmark; 3Hillerød University Hospital, Copenhagen, Denmark. Contact e-mail: [email protected] Background: Globally, hysterectomy is a very common surgical procedure among women and approximately 80% of hysterectomies are done on benign indications to increase quality of life. Recent studies have indicated that hysterectomy could be associated with increased risk for dementia. To determine whether hysterectomy is a risk factor for dementia, we conducted a nationwide historical cohort study using the Danish national registers. Methods: From the Danish Civil Registration System, a cohort was selected consisting of all female Danish residents born before 1966 (at least 40 years old in 2006). By linking data with the Danish hospital registers, this cohort was followed from January 1st, 1977 or the age of 40, whichever came later, until date of dementia diagnosis registered for the first time in the hospital registers,
date of death, date of immigration, or December 31st, 2006, whichever came first. Women diagnosed with dementia before 1977 and women who have undergone oophorectomies were excluded. The relative risks for developing dementia were stratified by age at hysterectomies (2030, 30-40, 40-45, 45-49, 50-55, 55-59, 60-69, 70-79, 80-89, 90 and above). All the relative risks were controlled for age at dementia diagnosis (one-year strata) and calendar year (one-year strata) at dementia diagnosis. Results: The cohort consisted of 2,313,388 females with 37,186,116 person-years of follow-up. From 1977 to 2006, there were 95,257 dementia cases and 1,309 hysterectomies. Compared to referent women of the same age group who had never had hysterectomies, women who had undergone hysterectomies had an increased risk of dementia, but only with early-onset dementia (dementia onset between 40-50 years old) (1.37, CI: 1.06, 1.77). Within this group of early-onset dementia, the younger was the age at hysterectomy, the greater was the risk. Conclusions: Premenopausal hysterectomy was associated with early-onset dementia, regardless of ovarian status. The effect of hysterectomy on early-onset dementia was age-dependent. Further studies are needed to confirm this association and to clarify the mechanisms underlying this association. As hysterectomy is such a common operation among women worldwide, this is an area where risk modification may have a great public health impact. P4-126
METABOLIC SYNDROME, SUCCESSFUL AND PATHOLOGICAL NEUROAGING IN A STROKEFREE ELDERLY POPULATION
Matheus Roriz-Cruz1, Idiane Rosset1, Teiji Sakagami2, Jarbas S. Roriz-Filho3, Eliane P. Morais1, Rosalina A. P. Rodrigues3, Kozo Matsubayashi2, 1Federal University of Rio Grande do Sul State, Brazil, Porto Alegre, Brazil; 2Kyoto University, Kyoto, Japan; 3 University of Sa˜o Paulo, Sa˜o Paulo, Brazil. Contact e-mail: [email protected] Background: Large part of the age-related neurofunctional decline is associated with stroke and cerebral microangiopathy. Metabolic Syndrome (Met.S) is a risk factor for both of these cerebrovascular disorders. It is unknown if Met.S is associated with neurofunctional decline in a stroke-free population. Methods: We evaluated 422 healthy community-dwelling elderly (ⱖ 60) in Brazil. Mini-Mental State Examination (MMSE), Geriatric Depression Scale (GDS), ‘Up&Go’ and Functional Reach tests, Executive Function and Activities of Daily Living were assessed. All reported values have P ⬍ 0.05. Results: Met.S was present in 39.3% of the subjects. Neurofunctional scores were significantly lower in the Met.S than in the control group (F: 2.7-5.9). Age alone explained 47% of all MMSE variance in the Met.S group, but just 12.8% among controls (P ⬍ 0.001 for difference). Age accounted for 18.7% of the variance on GDS in the Met.S group, whereas GDS score was not related to age in the control group. Analogously, the control group tended to have a more homogeneous score through all ages for every variable, whereas the Met.S group tended to have lower performances with increasing age (P ⬍ 0.05 for all differences). Adjusting for individual Met.S components reduced the power of the correlations between the number of Met.S components and evaluated neurofunctional scores (from R: 0.130-0.227 to R: 0.101-0.183), but did not eliminate their statistical significances, evidencing a synergism. The strong inverse correlation between the MMSE and GDS scales was restricted to the Met.S group (B: 0.38; P ⱕ 0.001). Conclusions: Met.S was independently associated with lower cognitive, executive, neuromotor and functional scores, and with more depressive symptoms. Association between cognitive dysfunction and depressive symptoms were explained in terms of Met.S-associated cerebrovascular risk. Met.S might be a major determinant of ‘successful’ or ‘pathological’ neuroaging in western societies.
Poster Presentations P4:
T707
were investigated for their health status/habits at midlife and re-examination. Results: Persons who participated in leisure time physical activity at midlife tended to have larger total brain volume ( 0.12; 95% CI -0.171.16, p⫽0.10) later in life than the more sedentary persons even after adjustments for socio-demographic and vascular factors, apoE ⑀4 genotype, smoking, diagnosis of dementia or mild cognitive impairment and cerebrospinal fluid/white matter/grey matter volumes. Interestingly, GM volume was significantly larger among the active ( 0.19; 95% CI 0.071.48, p⫽0.03), whereas the association between midlife physical activity and larger WM volume became non-significant after full adjustments. Further, the differences in the GM density between the active and sedentary groups localized mainly in frontal lobes. Finally, there was no significant association between midlife physical activity and severe WML later in life after full adjustments. Conclusions: Midlife physical activity might have an effect on total brain and GM volumes later in life, while there might not be an association between midlife physical activity and either WM volume or WML later in life. However, more studies with different methods are warranted for further understanding about the association between physical activity and structural brain changes. P4-128
AGING-RELATED PRIMARY BRAIN ATROPHY: FREQUENCY, ASSOCIATION WITH DEMENTIA, AND RISK FACTORS IN THE HONOLULU-ASIA AGING STUDY
Lon R. White1,2, Helen Petrovitch1,2, Webster Ross3, Jane H. Ueyhara-Lock1,4, Kamal Masaki1,4, Aaron McMurtray4, SaJung Yun1, William Markesbery5, 1Pacific Health Research Institute, Honolulu, HI, USA; 2Kuakini Medical Center, Honolulu, HI, USA; 3 Honolulu Veteran’s Administration, Honolulu, HI, USA; 4University of Hawaii School of Medicine, Honolulu, HI, USA; 5University of Kentucky School of Medicine, Lexington, KY, USA. Contact e-mail: [email protected]
P4-127
THE EFFECT OF MIDLIFE PHYSICAL ACTIVITY ON SUBSEQUENT STRUCTURAL BRAIN CHANGES
Suvi Rovio1, Gabriela Spulber2, Lasse J. Nieminen2, Eini Niskanen2, Bengt Winblad1, Jaakko Tuomilehto3, Aulikki Nissinen3, Hilkka Soininen2, Miia Kivipelto1, 1Karolinska Institutet, Stockholm, Sweden; 2University of Kuopio, Kuopio, Finland; 3National Public Health Institute, Helsinki, Finland. Contact e-mail: [email protected] Background: Physical activity has been associated with decreased risk of dementia in recent studies. Simultaneously, several dementia risk factors have been associated with WML and/or brain atrophy in magnetic resonance images (MRI), but the role of physical activity is unclear. In this study, we aimed at clarifying the associations between midlife physical activity and subsequent structural brain changes using MRI. Methods: The CAIDE subjects were randomly selected from population based samples first studied in 1972-1987, and re-examined in 1998 (average follow-up time 21 years). For this study, a subpopulation of 91 persons was scanned at the re-examination with Siemens Magnetom 1.5T MR scanner, and T1-weighted images were used to investigate grey matter (GM) density using voxel-based morphometry. WML were assessed on FLAIR-images using a semi-quantitative visual rating scale. Additionally, all participants
Background: Brain atrophy at autopsy is often associated with Alzheimer lesions, microinfarcts or lacunes, cortical Lewy bodies, or hippocampal atrophy. When observed in elderly decedents in the absence of any of these or other specific lesions it is provisionally designated aging-related primary brain atrophy (ARPBA). Methods: To facilitate analyses of brain atrophy at autopsy we developed a composite index comparing brain mass and mantle thickness with imputed estimates of the same measures prior to onset of atrophy by reference to estimated intracranial volumes (contributing 50% and 40% to the composite index). A neuropathologist’s qualitative assessment of neuronal loss in 8 neocortical gray matter regions contributed an additional 10% to the index. Results: Moderate (n⫽18) or severe (n⫽8) ARPBR was identified in 14.5% of 181 HAAS research protocol brain autopsies in which none of the lesions mentioned were present at clinically significant levels. In these 181 decedents severity of atrophy was significantly (p⬍0.0001) associated with cognitive impairment or dementia in the final years of life, controlling for education, ApoE4, and levels (all negligible) of neocortical neurofibrillary tangles, neuritic plaques, microvascular infarcts, and Lewy bodies. Among decedents with mild or negligible atrophy, 8% had been demented (by DSMIII-R criteria) and another 26% had definite cognitive impairment. Among decedents with moderate ARPBA, 28% had been demented and an additional 22% were impaired. Among decedents with severe ARPBA, 25% had been demented while an additional 37.5% had been cognitively impaired. Most of the dementia cases had been attributed to Alzheimer’s disease during life. An extensive search for risk factors associated with atrophy severity in these 181 decedents identified only advanced age (p⫽0.008) and elevated midlife systolic blood pressure (p⫽0.002). Conclusions: The pathogenesis of ARPBA is not understood. Further investigation may identify histopathologic changes that will allow more precise diagnoses. Since one type of pathologic process rarely precludes others, it is likely that the atrophy observed in older decedents with Alzheimer lesions, microvascular ischemic lesions, hippocampal sclerosis, or cortical