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LETTERS TO THE EDITOR
JANUARY 2015–VOL. 63, NO. 1
6. Naughton C, Drennan J, Lyons I et al. Elder abuse and neglect in Ireland: Results from a national prevalence survey. Age Ageing 2012;41:98–103. 7. Sooryanarayana R, Choo W-Y, Hairi NN. A review on the prevalence and measurement of elder abuse in the community. Trauma Violence Abuse 2013;14:316–325. 8. Esther E, Shahrul K, Low WY. Elder abuse: A silent cry. Malaysian J Psychiatry 2006;14:29–34. 9. Aishath M, Harun MH. Elder Abuse in Malaysia. Malayan Law J Articles 2010;6:viii. 10. Hamid TA, Za SF, Mansor M et al. Cohort Differences in Perceptions of Elder Maltreatment. South East Asian Conference on Ageing 2010, July 17–18, 2010, Grand Millenium Hotel, Kuala Lumpur, Malaysia [on-line]. Available at http://seaca2010.files.wordpress.com/2010/07/ microsoft-powerpoint-perception-tah-sfza-et-al-17-July-2010.pdf Accessed October 3, 2011.
LOWER GLOMERULAR FILTRATION RATE ASSOCIATED WITH WHITE MATTER HYPERINTENSITIES MORE IN VASCULAR DEMENTIA THAN IN ALZHEIMER’S DISEASE To the Editor: White matter hyperintensities (WMHs) from cerebral small vessel disease (SVD) can indicate greater risk of stroke and dementia. Aging and hypertension are major risk factors for cerebral SVD, but these fail to account for all of the risk. Chronic kidney disease (CKD), defined according to estimated glomerular filtration rate (eGFR), is widely recognized as an independent risk factor for stroke and subclinical vascular diseases, such as SVD.1 Moreover, recent research has supported a causal role of inflammation, endothelial dysfunction, and oxidative stress in the development of vascular disease.2 These processes are all characteristic of CKD3 and may also be found in vascular dementia (VaD) and Alzheimer’s disease (AD).4 Data regarding the role of low eGFR in the development of WMHs in AD and VaD are limited.5 It was hypothesized that lower eGFR would be more strongly associated with WMHs in VaD than AD, independent of vascular risk factors.
METHODS This study formed part of the ongoing Clinical Research Center for Dementia of South Korea Study (CREDOS), a large, prospective, hospital-based cohort study designed to
JAGS
assess the occurrence of and risk factors for cognitive disorders, established in November 2005. Further information regarding CREDOS has been previously published.6 Data from 952 CREDOS participants with measurements of eGFR, hemoglobin, and albumin were retrospectively analyzed. All participants had a clinical interview and blood test on the same day. All blood parameters were analyzed according to the standard protocols of the biochemistry laboratories that participated in the study, which operate under a rigorous quality control program. Kidney function was indicated according to eGFR, which was calculated in mL/min per 1.73 m2 using the simplified Modification of Diet in Renal Disease equation (186.3 9 (serum creatinine) 1.154 9 age 0.203, multiplied by 0.742 for women).7 Anemia was defined according to World Health Organization criteria as hemoglobin concentrations less than 12 g/dL for women and 13 g/dL for men.8 A standardized neuropsychological battery, the Seoul Neuropsychological Screening Battery—Dementia version, was used to assess all participants. Magnetic resonance imaging (MRI) was conducted in accordance with an acquisition protocol developed for CREDOS. MRI scans included transaxial T2, T1-weighted, gradient-echo, fluid-attenuated inversion recovery (FLAIR), and coronal T1-weighted images. The severity of WMHs was evaluated according to modified Fazekas9 and Scheltens10 criteria, using the T2 axial or FLAIR images. WMHs were examined separately in the periventricular white matter and deep white matter. Logistic regression analysis was conducted in individuals with normal cognitive function, mild cognitive impairment (MCI), AD, and VaD to evaluate the effect of eGFR on severity of WMHs. Age, sex, history of hypertension, diabetes mellitus, hyperlipidemia, and ischemic heart disease were included as covariates.
RESULTS Of 952 older adults, 162 had normal cognitive function, 237 had MCI, 330 had AD, and 224 had VaD. The prevalence of hypertension and stroke was higher in participants with VaD. Logistic regression analysis indicated that the association between age, hypertension, and moderate WMHs was statistically significant in participants with normal cognitive function. Multivariate logistic regression analysis showed a significant association between hypoalbuminemia and moderate WMHs after adjustment for age,
Table 1. Moderate White Matter Hyperintensities (WMHs) in Normal Cognitive Function, Mild Cognitive Impairment (MCI), and Alzheimer’s Disease (AD), and Severe WMHs in Vascular Dementia (VaD): Multivariate Logistic Regression Analysis Normal Cognitive Function Risk Factor
Chronic kidney disease Hypoalbuminemia Anemia Hypertension Age P < a.01, b.05.
MCI
AD
VaD
Odds Ratio (95% Confidence Interval)
4.50 1.03 0.31 3.74 1.13
(0.66–30.64) (0.30–3.48) (0.05–2.01) (1.58–8.81)a (1.05–1.21)a
0.97 2.39 0.72 1.07 1.09
(0.39–2.41) (1.12–5.08)b (0.28–1.85) (0.54–2.14) (1.04–1.15)a
1.63 1.79 0.48 0.59 1.11
(0.83–3.17) (1.01–3.18)b (0.22–1.04) (0.33–1.05) (1.07–1.16)a
2.28 0.67 1.08 1.40 1.02
(0.95–5.48) (0.32–1.37) (0.48–2.46) (0.71–2.77) (0.98–1.07)
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JANUARY 2015–VOL. 63, NO. 1
sex, and cardiovascular risk factors in participants with MCI and AD (Table 1). The association between eGFR and WMHs in participants with VaD was significant but was attenuated when adjusting for vascular risk factors.
DISCUSSION Vascular risk factors such as hypertension, dietary fat intake, high cholesterol, and obesity have emerged as important influences on the risk of VaD and AD, but there is little evidence to support the view that these vascular risk factors have the same influence on WMHs in both types of dementia. The present study provided an opportunity to examine the relationship between WMHs, eGFR, and hypoalbuminemia in AD and VaD and revealed that low eGFR was associated more strongly with WMHs in VaD than with MCI or AD. Hypoalbuminemia was also associated with WMHs in MCI and AD. SVD is an important pathophysiological mechanism in dementia but does not lend itself to categorical diagnostic labels. Hypoalbuminemia might be useful for differentiating the influence of SVD on dementia. Kang Soo Lee, MD, PhD Department of Psychiatry, CHA University College of Medicine, Gangnam Medical Center, CHAUM Life Center, Seoul, Korea Duk L. Na, MD, PhD Sang Won Seo, MD, PhD Department of Neurology, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul, Korea
LETTERS TO THE EDITOR
183
collection, endpoint adjudication, interpretation of data, statistical analysis. Choi: study coordinator, study concept, endpoint adjudication, interpretation of data. Oh: study concept, interpretation of data. Sponsor’s Role: None.
REFERENCES 1. Mogi M, Horiuchi M. Clinical interaction between brain and kidney in small vessel disease. Cardiol Res Pract 2011;2011:306189. 2. Landmesser U, Spiekermann S, Dikalov S, et al. Vascular oxidative stress and endothelial dysfunction in patients with chronic heart failure: Role of xanthine-oxidase and extracellular superoxide dismutase. Circulation 2002;106:3073–3078. 3. Dhaun N, Goddard J, Webb DJ. The endothelin system and its antagonism in chronic kidney disease. J Am Soc Nephrol 2006;17:943–955. 4. Grammas P, Ovase R. Inflammatory factors are elevated in brain microvessels in Alzheimer’s disease. Neurobiol Aging 2001;22:837–842. 5. Helmer C, Stengel B, Metzger M, et al. Chronic kidney disease, cognitive decline, and incident dementia: The 3C study. Neurology 2011;77:2043– 2051. 6. Park HK, Na DL, Han SH, et al. Clinical characteristics of a nationwide hospital-based registry of mild-to-moderate Alzheimer’s disease patients in Korea: A CREDOS (Clinical Research Center for Dementia of South Korea) study. J Korean Med Sci 2011;26:1219–1226. 7. Levey AS, Bosch JP, Lewis JB, et al. A more accurate method to estimate glomerular filtration rate from serum creatinine: A new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med 1999;130:461–470. 8. Beghe C, Wilson A, Ershler WB. Prevalence and outcomes of anemia in geriatrics: A systematic review of the literature. Am J Med 2004;116(Suppl 7A):S3–S10. 9. Fazekas F, Chawluk JB, Alavi A, et al. MR signal abnormalities at 1.5 T in Alzheimer’s dementia and normal aging. AJR Am J Roentgenol 1987;149:351–356. 10. Scheltens P, Barkhof F, Leys D, et al. A semiquantative rating scale for the assessment of signal hyperintensities on magnetic resonance imaging. J Neurol Sci 1993;114:7–12.
Jong Hun Kim, MD, PhD Department of Neurology, Ilsan Hospital, National Health Insurance Corporation, Goyang-si, Korea Seong Hye Choi, MD, PhD Department of Neurology, College of Medicine, Inha University, Incheon, Korea Byoung Hoon Oh, MD, PhD Department of Psychiatry, College of Medicine, Yonsei University, Seoul, Korea Sang Joon Son, MD, PhD Chang Hyung Hong, MD, PhD Department of Psychiatry, School of Medicine, Ajou University, Suwon-si, Korea Institute of Aging, Ajou University Medical Center, Suwon, Korea
ACKNOWLEDGMENTS Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this paper. Author Contributions: Hong, Son, Lee: study concept, design, interpretation of data, statistical analysis, writing of manuscript. Na, Seo, Kim: acquisition of subjects, data
CESSATION OF DRIVING IS RARE IN OLDER DRIVERS SEEN IN THE EMERGENCY DEPARTMENT AFTER A MOTOR VEHICLE COLLISION: A PROSPECTIVE COHORT STUDY To the Editor: Motor vehicle collisions (MVCs) are one of the leading causes of fatal injury in older adults and, when not fatal, frequently result in persistent pain and functional decline.1,2 A systematic approach to the identification of high-risk older drivers is needed to decrease MVC-related morbidity and mortality.3 Performancebased measures or questionnaires can be used to identify high-risk older drivers,4,5 such as those with cognitive or functional impairments,6,7 but which events should prompt an evaluation is unclear. MVCs, which result in an estimated 250,000 U.S. emergency department (ED) visits by older adults each year,8 would seem to be an important indicator of risk for future MVCs, but whether older drivers stop driving after experiencing an MVC is not known. This study was designed to characterize cessation of driving in older drivers presenting to the ED for evaluation after a MVC. Data from a prospective study of adults aged 65 and older who received care after a MVC in one of eight U.S.
Copyright of Journal of the American Geriatrics Society is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
LETTERS TO THE EDITOR
JANUARY 2015–VOL. 63, NO. 1
6. Naughton C, Drennan J, Lyons I et al. Elder abuse and neglect in Ireland: Results from a national prevalence survey. Age Ageing 2012;41:98–103. 7. Sooryanarayana R, Choo W-Y, Hairi NN. A review on the prevalence and measurement of elder abuse in the community. Trauma Violence Abuse 2013;14:316–325. 8. Esther E, Shahrul K, Low WY. Elder abuse: A silent cry. Malaysian J Psychiatry 2006;14:29–34. 9. Aishath M, Harun MH. Elder Abuse in Malaysia. Malayan Law J Articles 2010;6:viii. 10. Hamid TA, Za SF, Mansor M et al. Cohort Differences in Perceptions of Elder Maltreatment. South East Asian Conference on Ageing 2010, July 17–18, 2010, Grand Millenium Hotel, Kuala Lumpur, Malaysia [on-line]. Available at http://seaca2010.files.wordpress.com/2010/07/ microsoft-powerpoint-perception-tah-sfza-et-al-17-July-2010.pdf Accessed October 3, 2011.
LOWER GLOMERULAR FILTRATION RATE ASSOCIATED WITH WHITE MATTER HYPERINTENSITIES MORE IN VASCULAR DEMENTIA THAN IN ALZHEIMER’S DISEASE To the Editor: White matter hyperintensities (WMHs) from cerebral small vessel disease (SVD) can indicate greater risk of stroke and dementia. Aging and hypertension are major risk factors for cerebral SVD, but these fail to account for all of the risk. Chronic kidney disease (CKD), defined according to estimated glomerular filtration rate (eGFR), is widely recognized as an independent risk factor for stroke and subclinical vascular diseases, such as SVD.1 Moreover, recent research has supported a causal role of inflammation, endothelial dysfunction, and oxidative stress in the development of vascular disease.2 These processes are all characteristic of CKD3 and may also be found in vascular dementia (VaD) and Alzheimer’s disease (AD).4 Data regarding the role of low eGFR in the development of WMHs in AD and VaD are limited.5 It was hypothesized that lower eGFR would be more strongly associated with WMHs in VaD than AD, independent of vascular risk factors.
METHODS This study formed part of the ongoing Clinical Research Center for Dementia of South Korea Study (CREDOS), a large, prospective, hospital-based cohort study designed to
JAGS
assess the occurrence of and risk factors for cognitive disorders, established in November 2005. Further information regarding CREDOS has been previously published.6 Data from 952 CREDOS participants with measurements of eGFR, hemoglobin, and albumin were retrospectively analyzed. All participants had a clinical interview and blood test on the same day. All blood parameters were analyzed according to the standard protocols of the biochemistry laboratories that participated in the study, which operate under a rigorous quality control program. Kidney function was indicated according to eGFR, which was calculated in mL/min per 1.73 m2 using the simplified Modification of Diet in Renal Disease equation (186.3 9 (serum creatinine) 1.154 9 age 0.203, multiplied by 0.742 for women).7 Anemia was defined according to World Health Organization criteria as hemoglobin concentrations less than 12 g/dL for women and 13 g/dL for men.8 A standardized neuropsychological battery, the Seoul Neuropsychological Screening Battery—Dementia version, was used to assess all participants. Magnetic resonance imaging (MRI) was conducted in accordance with an acquisition protocol developed for CREDOS. MRI scans included transaxial T2, T1-weighted, gradient-echo, fluid-attenuated inversion recovery (FLAIR), and coronal T1-weighted images. The severity of WMHs was evaluated according to modified Fazekas9 and Scheltens10 criteria, using the T2 axial or FLAIR images. WMHs were examined separately in the periventricular white matter and deep white matter. Logistic regression analysis was conducted in individuals with normal cognitive function, mild cognitive impairment (MCI), AD, and VaD to evaluate the effect of eGFR on severity of WMHs. Age, sex, history of hypertension, diabetes mellitus, hyperlipidemia, and ischemic heart disease were included as covariates.
RESULTS Of 952 older adults, 162 had normal cognitive function, 237 had MCI, 330 had AD, and 224 had VaD. The prevalence of hypertension and stroke was higher in participants with VaD. Logistic regression analysis indicated that the association between age, hypertension, and moderate WMHs was statistically significant in participants with normal cognitive function. Multivariate logistic regression analysis showed a significant association between hypoalbuminemia and moderate WMHs after adjustment for age,
Table 1. Moderate White Matter Hyperintensities (WMHs) in Normal Cognitive Function, Mild Cognitive Impairment (MCI), and Alzheimer’s Disease (AD), and Severe WMHs in Vascular Dementia (VaD): Multivariate Logistic Regression Analysis Normal Cognitive Function Risk Factor
Chronic kidney disease Hypoalbuminemia Anemia Hypertension Age P < a.01, b.05.
MCI
AD
VaD
Odds Ratio (95% Confidence Interval)
4.50 1.03 0.31 3.74 1.13
(0.66–30.64) (0.30–3.48) (0.05–2.01) (1.58–8.81)a (1.05–1.21)a
0.97 2.39 0.72 1.07 1.09
(0.39–2.41) (1.12–5.08)b (0.28–1.85) (0.54–2.14) (1.04–1.15)a
1.63 1.79 0.48 0.59 1.11
(0.83–3.17) (1.01–3.18)b (0.22–1.04) (0.33–1.05) (1.07–1.16)a
2.28 0.67 1.08 1.40 1.02
(0.95–5.48) (0.32–1.37) (0.48–2.46) (0.71–2.77) (0.98–1.07)
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JANUARY 2015–VOL. 63, NO. 1
sex, and cardiovascular risk factors in participants with MCI and AD (Table 1). The association between eGFR and WMHs in participants with VaD was significant but was attenuated when adjusting for vascular risk factors.
DISCUSSION Vascular risk factors such as hypertension, dietary fat intake, high cholesterol, and obesity have emerged as important influences on the risk of VaD and AD, but there is little evidence to support the view that these vascular risk factors have the same influence on WMHs in both types of dementia. The present study provided an opportunity to examine the relationship between WMHs, eGFR, and hypoalbuminemia in AD and VaD and revealed that low eGFR was associated more strongly with WMHs in VaD than with MCI or AD. Hypoalbuminemia was also associated with WMHs in MCI and AD. SVD is an important pathophysiological mechanism in dementia but does not lend itself to categorical diagnostic labels. Hypoalbuminemia might be useful for differentiating the influence of SVD on dementia. Kang Soo Lee, MD, PhD Department of Psychiatry, CHA University College of Medicine, Gangnam Medical Center, CHAUM Life Center, Seoul, Korea Duk L. Na, MD, PhD Sang Won Seo, MD, PhD Department of Neurology, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul, Korea
LETTERS TO THE EDITOR
183
collection, endpoint adjudication, interpretation of data, statistical analysis. Choi: study coordinator, study concept, endpoint adjudication, interpretation of data. Oh: study concept, interpretation of data. Sponsor’s Role: None.
REFERENCES 1. Mogi M, Horiuchi M. Clinical interaction between brain and kidney in small vessel disease. Cardiol Res Pract 2011;2011:306189. 2. Landmesser U, Spiekermann S, Dikalov S, et al. Vascular oxidative stress and endothelial dysfunction in patients with chronic heart failure: Role of xanthine-oxidase and extracellular superoxide dismutase. Circulation 2002;106:3073–3078. 3. Dhaun N, Goddard J, Webb DJ. The endothelin system and its antagonism in chronic kidney disease. J Am Soc Nephrol 2006;17:943–955. 4. Grammas P, Ovase R. Inflammatory factors are elevated in brain microvessels in Alzheimer’s disease. Neurobiol Aging 2001;22:837–842. 5. Helmer C, Stengel B, Metzger M, et al. Chronic kidney disease, cognitive decline, and incident dementia: The 3C study. Neurology 2011;77:2043– 2051. 6. Park HK, Na DL, Han SH, et al. Clinical characteristics of a nationwide hospital-based registry of mild-to-moderate Alzheimer’s disease patients in Korea: A CREDOS (Clinical Research Center for Dementia of South Korea) study. J Korean Med Sci 2011;26:1219–1226. 7. Levey AS, Bosch JP, Lewis JB, et al. A more accurate method to estimate glomerular filtration rate from serum creatinine: A new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med 1999;130:461–470. 8. Beghe C, Wilson A, Ershler WB. Prevalence and outcomes of anemia in geriatrics: A systematic review of the literature. Am J Med 2004;116(Suppl 7A):S3–S10. 9. Fazekas F, Chawluk JB, Alavi A, et al. MR signal abnormalities at 1.5 T in Alzheimer’s dementia and normal aging. AJR Am J Roentgenol 1987;149:351–356. 10. Scheltens P, Barkhof F, Leys D, et al. A semiquantative rating scale for the assessment of signal hyperintensities on magnetic resonance imaging. J Neurol Sci 1993;114:7–12.
Jong Hun Kim, MD, PhD Department of Neurology, Ilsan Hospital, National Health Insurance Corporation, Goyang-si, Korea Seong Hye Choi, MD, PhD Department of Neurology, College of Medicine, Inha University, Incheon, Korea Byoung Hoon Oh, MD, PhD Department of Psychiatry, College of Medicine, Yonsei University, Seoul, Korea Sang Joon Son, MD, PhD Chang Hyung Hong, MD, PhD Department of Psychiatry, School of Medicine, Ajou University, Suwon-si, Korea Institute of Aging, Ajou University Medical Center, Suwon, Korea
ACKNOWLEDGMENTS Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this paper. Author Contributions: Hong, Son, Lee: study concept, design, interpretation of data, statistical analysis, writing of manuscript. Na, Seo, Kim: acquisition of subjects, data
CESSATION OF DRIVING IS RARE IN OLDER DRIVERS SEEN IN THE EMERGENCY DEPARTMENT AFTER A MOTOR VEHICLE COLLISION: A PROSPECTIVE COHORT STUDY To the Editor: Motor vehicle collisions (MVCs) are one of the leading causes of fatal injury in older adults and, when not fatal, frequently result in persistent pain and functional decline.1,2 A systematic approach to the identification of high-risk older drivers is needed to decrease MVC-related morbidity and mortality.3 Performancebased measures or questionnaires can be used to identify high-risk older drivers,4,5 such as those with cognitive or functional impairments,6,7 but which events should prompt an evaluation is unclear. MVCs, which result in an estimated 250,000 U.S. emergency department (ED) visits by older adults each year,8 would seem to be an important indicator of risk for future MVCs, but whether older drivers stop driving after experiencing an MVC is not known. This study was designed to characterize cessation of driving in older drivers presenting to the ED for evaluation after a MVC. Data from a prospective study of adults aged 65 and older who received care after a MVC in one of eight U.S.
Copyright of Journal of the American Geriatrics Society is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
