1、Objective cardiac markers in dementia: Results from the Kerala-Einstein studyS Buss, MD1, ML Noone, DM3, R Tsai, MD1, B Johnson, MBBS3, VG Pradeep, DM3, KASalam, DM3, PS Mathuranath, DM4, and J Verghese, MBBS11Department of Neurology, Albert Einstein College of Medicine, Bronx, NY, USA2Department of
2、 Epidemiology Cognitive impairment; Dementia; Echocardiography; Electrocardiography;EpidemiologyAlzheimers disease (AD) and vascular dementia (VaD), the most common causes ofdementia worldwide, share many vascular risk factors. Atrial fibrillation and myocardialinfarction on electrocardiogram (ECG)
3、has been associated with AD and VaD 1, 2. Leftventricular hypertrophy (LVH) on echocardiogram was linked to cognitive dysfunction 3,4. Echocardiographic LVH and aortic valve (AV) regurgitation are related to AD 5.However, previous studies are limited by small samples 5, 6, restriction to single dise
4、ases3, 6, not examined both ECG and echocardiogram abnormalities 16, or focused onsingle ECG abnormalities 1, 2. Importantly, almost no research on cardiac markers indementia has been conducted in developing countries.Hence, we studied association of ECG and echocardiogram abnormalities with dementi
5、a inolder adults participating at the Kozhikode site of the Kerala Einstein Study (KES) in thesouthern Indian state of Kerala. Participants with dementia were identified from neurologyclinics. A control sample of cognitively normal adults was recruited from relatives ofpatients and patients with non
6、-cognitive complaints. Inclusion criterion was age 55 andolder. Exclusion criteria included severe audiovisual loss or presence of active medical or 2012 Elsevier Ireland Ltd. All rights reserved.Corresponding author: Joe Verghese, M.D., Division of Cognitive available in PMC 2014 July 31.Published
7、in final edited form as:Int J Cardiol. 2013 July 31; 167(2): 595596. doi:10.1016/j.ijcard.2012.09.220.NIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author Manuscriptpsychiatric illnesses. Informed consent was obtained from all participants and studyprotocols were approved by the local insti
8、tutional review board.Standard 12-lead ECG was analyzed following the Minnesota code classification by a studyclinician, blinded to dementia status. The following abnormalities were reported: rhythmabnormalities, LVH, significant ST and T wave changes, Q waves, heart block, and bundlebranch block. M
9、ajor ECG abnormalities was defined as presence of any one of thefollowing: Q-QS wave abnormalities, LVH, Wolff-Parkinson-White syndrome, completebundle branch block or intraventricular block, atrial fibrillation or atrial flutter, or major ST-T changes. Agreement with original classification in a ra
10、ndom sample of 5% of baselineECG read by an independent cardiologist was good to excellent (Intra Class Correlations0.45 to 0.93).Transthoracic 2D echocardiograms were done by two cardiologists, who were not part of theKES team, and blinded to cognitive status. We examined LVH, valvular lesions and
11、reducedleft ventricular ejection fraction.Descriptive statistics were used to compare dependent variables by dementia status andsubtypes. Logistic regression analysis was used to report odds ratios (OR) with 95%confidence intervals (CI) for the association of ECG and echocardiographic abnormalitiesw
12、ith dementia, adjusted for age, gender, and years of education.Of the 360 participants enrolled in KES, 305 received ECG and 302 echocardiograms. Ofthe 305 subjects, 161 were men (52.8%), mean age was 68.4 years, and mean education 8years. Sixty-six participants were diagnosed with dementia at conse
13、nsus case conferences:34 AD, 29 VaD, and three unclassified.Baseline characteristics are presented in Table 1. Participants with dementia, AD, and VaDwere older, less educated, and had worse cognitive scores than controls. The AD group hadmore women. There was a higher prevalence of hypertension and
14、 cerebrovascular disease inVaD. AD patients had lower prevalence of ischemic heart disease than controls.Common ECG abnormalities in dementia subjects were ST/T wave changes (16.7% vs.7.1% controls), LVH (13.6% vs. 3.8%), Q waves (3.0% vs. 3.3%), and bundle branch block(3.0% vs. 3.8%). There was no
15、heart block. Only one control had atrial fibrillation.Prevalence of major ECG abnormalities was 28.8% in dementia and 15.9% in controls (p =0.037).Table 2 shows that LVH was associated with dementia (OR 4.53, 95% CI 1.5213.51). LVH(OR 11.74, 85% CI 3.1543.71) and ST/T abnormalities (OR 3.06, 95% CI
16、1.068.85) wereassociated with VaD. Major ECG abnormalities were associated with VaD (OR 4.25, 95%CI 1.7910.11). The results were not materially different after excluding controls with mildcognitive impairment syndrome.Common echocardiographic findings in dementia were LVH (43.8% vs. 35.3% controls),
17、AV sclerosis (32.8% vs. 16.5%), AV regurgitation (21.9% vs. 9.7%), and reduced ejectionfraction (10.9% vs. 8.8%). VaD was associated with LVH (OR 4.33, 95% CI 1.7910.45).Valvular abnormalities and reduced ejection fraction were not associated with dementiastatus.In this clinic-based sample of Indian
18、 seniors cardiac markers were associated with dementia,especially VaD. Previous cardiac marker studies have focused on AD 1, 2, 5 or do notdistinguish dementia subtypes 4, 6. ECG and echocardiogram showed different strengthsof association, even for the same marker. For instance, LVH on ECG (OR 11.74
19、) was moreBuss et al. Page 2Int J Cardiol. Author manuscript; available in PMC 2014 July 31.NIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author Manuscriptstrongly associated with VaD than echocardiographic LVH (OR 4.33). Whileechocardiogram and ECG complement each other, some degree of div
20、ergence is to beexpected since they measure different aspects of cardiac function. Our findings showed thatmajor ECG abnormalities are associated with VaD. This variable may prove useful inidentifying dementia as well as cardiac risk 7.Our results are supported by a study that showed ECG LVH predict
21、ed stroke, even afteradjusting for echocardiographic LVH 8. Cardiac markers were not related to AD in ourstudy. A previous study in a smaller sample showed an association between AD andechocardiographic LVH and valvular abnormalities 5. In a population based sample,unrecognized (Q-wave) myocardial i
22、nfarction was associated with risk of AD and VaD inmen but not women 2. We did not differentiate between clinical and occult myocardialinfarctions.Strengths of our study include the large sample, dementia diagnosis blinded to cardiacfindings, standardized assessments, and homogeneous population. The
23、 cross-sectionaldesign limits causal inferences. Reverse causality needs to be considered; cardiacabnormalities can result from dementia pathology or strokes 9. Longitudinal studies areneeded to validate our findings.Cardiac studies are not currently recommended in dementia work up. If our findings
24、arevalidated, ECG could be included in dementia work up or used to stratify cognitive risk.Since our findings suggest that ECG may contain greater prognostic value thanechocardiogram and is widely available, technically easy, and inexpensive, it may be avaluable asset to identify and predict dementi
25、a risk in resource poor settings.The authors of this manuscript have certified that they comply with the Principles of EthicalPublishing in the International Journal of Cardiology 10.AcknowledgmentsSources of Funding: National Institute on Aging grant (R01 AG039330-01).References1. Ott A, Breteler M
26、M, de Bruyne MC, van Harskamp F, Grobbee DE, Hofman A. Atrial fibrillationand dementia in a population-based study. The Rotterdam Study. Stroke. 1997; 28:31621.PubMed: 90406822. Ikram MA, van Oijen M, de Jong FJ, et al. Unrecognized myocardial infarction in relation to risk ofdementia and cerebral s
27、mall vessel disease. Stroke. 2008; 39:14216. PubMed: 183234973. Hayakawa M, Yano Y, Kuroki K, et al. Independent Association of Cognitive Dysfunction WithCardiac Hypertrophy Irrespective of 24-h or Sleep Blood Pressure in Older Hypertensives. Am JHypertens. 2012; 25:657663. PubMed: 224219074. Scuter
28、i A, Coluccia R, Castello L, Nevola E, Brancati AM, Volpe M. Left ventricular mass increaseis associated with cognitive decline and dementia in the elderly independently of blood pressure.Eur Heart J. 2009; 30:15259. PubMed: 194068645. Reitz C, Brickman AM, Luchsinger JA, Wu WE, Small SA, Tang MX. F
29、requency of subclinicalheart disease in elderly persons with dementia. Am J Geriatr Cardiol. 2007; 16:1838. PubMed:174836716. Zuccala G, Cattel C, Manes-Gravina E, Di Niro MG, Cocchi A, Bernabei R. Left ventriculardysfunction: a clue to cognitive impairment in older patients with heart failure. J Ne
30、urol NeurosurgPsychiatry. 1997; 63:509512. PubMed: 93431337. Auer R, Bauer DC, Marques-Vidal P, et al. Association of major and minor ECG abnormalities withcoronary heart disease events. JAMA. 2012; 307:1497505. PubMed: 22496264Buss et al. Page 3Int J Cardiol. Author manuscript; available in PMC 201
31、4 July 31.NIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author Manuscript8. Kohsaka S, Sciacca RR, Sugioka K, Sacco RL, Homma S, Di Tullio MR. Additional impact ofelectrocardiographic over echocardiographic diagnosis of left ventricular hypertrophy for predictingthe risk of ischemic stroke.
32、 Am Heart J. 2005; 149:1816. PubMed: 156600519. Zulli R, Nicosia F, Borroni B, et al. QT dispersion and heart rate variability abnormalities inAlzheimers disease and in mild cognitive impairment. J Amer Geriatr Soc. 2005; 53:21359.PubMed: 1639889810. Coats AJ, Shewan LG. Statement on authorship and
33、publishing ethics in the international journal ofcardiology. Int J Cardiol. 2011; 153:23940. PubMed: 22108502Buss et al. Page 4Int J Cardiol. Author manuscript; available in PMC 2014 July 31.NIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author
34、 ManuscriptNIH-PA Author ManuscriptBuss et al. Page 5Table 1Baseline characteristics of subjects by dementia status.OverallControlsDementiaADVaDNN = 305N = 239N = 66N = 34N = 29Gender, men (%)52.8%54.8%45.5%35.3%*55.2%Age (years)68.46.467.35.772.47.3*71.07.8*73.16.2*Education (years)8.03.88.43.86.53
35、.4*5.83.6*7.03.1*Cognitive TestsMMSE24.47.027.43.213.56.1*14.55.8*12.96.2*ACE69.422.278.413.136.016.7*38.915.9*34.117.1*RAVLT3.83.54.83.30.10.6*0.20.8*0.00.0*Digit span test8.93.69.93.35.32.3*5.52.3*5.02.3*GDS4.93.44.63.46.23.3*5.73.26.83.5*Clinical Diagnosis (%)Hypertension31.6%30.1%36.9%20.6%58.6%
36、*Dyslipidemia12.2%12.6%10.8%8.8%13.8%Cerebrovascular disease8.2%5.0%20.0%*0.0%44.8%*Ischemic heart disease11.8%12.6%9.2%0.0%*20.7%Diabetes mellitus21.1%21.8%18.5%17.6%20.7%Values are mean standard deviation unless otherwise noted.* = p-value 0.05, computed using chi-square and t-testsMMSE: Mini-ment
37、al State Examination; ACE: Addenbrooke Cognitive Examination; RAVLT: Rey auditory verbal learning test; GDS: Geriatric depression scale.Int J Cardiol. Author manuscript; available in PMC 2014 July 31.NIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author ManuscriptBuss et al. Page 6Table 2Ass
38、ociation of ECG and echocardiographic findings with dementia and subtypes.All Dementia AD VaDECG abnormalitiesN 66 34 29Major ECG abnormalities 1.98 (0.984.00) 0.68 (0.212.17) 4.25 (1.7910.11)*LVH 4.53 (1.5213.51)* 0.89 (0.108.25) 11.74 (3.1543.71)*ST and T abnormalities 2.03 (0.825.00) 1.00 (0.253.
39、96) 3.06 (1.068.85)*Q waves 0.57 (0.103.15) 1.24 (0.226.95)Bundle branch block 1.14 (0.216.21) 1.26 (0.1411.25) 0.98 (0.109.16)Echocardiographic abnormalitiesN 64 32 29Ejection Fraction 55% 1.30 (0.483.53) 1.06 (0.284.07) 1.38 (0.394.85)LVH 1.53 (0.822.83) 0.60 (0.241.51) 4.33 (1.7910.45)*Aortic Reg
40、urgitation 1.82 (0.804.10) 1.60 (0.544.77) 2.35 (0.876.35)Aortic Sclerosis 1.67 (0.823.39) 1.64 (0.654.11) 1.87 (0.754.65)Mitral Regurgitation 0.43 (0.121.60) 0.62 (0.132.92) 0.25 (0.032.01)Mitral Calcification 0.83 (0.144.74) 1.02 (0.119.62)Results are shown as OR (95% CI), adjusted for age, gender, and education.*p-value 0.05,insufficient data.LVH: left ventricular hypertrophyInt J Cardiol. Author manuscript; available in PMC 2014 July 31.
