Hippocampal calcifications: risk factors and association with cognitive functioning E.J.M. de Brouwer, R. Kockelkoren, J.J. Claus, A. de Jonghe, M. Geerlings, T.E.F. Jongsma, W.P.Th.M. Mali, J. Hendrikse, P.A. de Jong, H.L. Koek University of Utrecht, the Netherlands
CONFLICT OF INTEREST DISCLOSURE I have no potential conflict of interest to report
Introduction • Dementia is a global health problem
Introduction • Multifactorial etiology: Alzheimer pathology, vascular lesions, Lewy bodies and inflammation • Most research focuses on neurodegeneration • Little research about vascular pathology in the hippocampus
Introduction
Introduction
Introduction
Hypothesis • Vasculopathy with fibrosis and calcification • Hippocampal atrophy • Leading to cognitive decline
Aim • To determine risk factors for hippocampal calcifications (HCC) • To determine the association between hippocampal calcifications and cognition
Methods • Outpatient memory clinic Tergooi hospital, the Netherlands • April 2009 – april 2015 • 2000 patients • Cognitive tests: CAMCOG, VAT, CDT, GDS • CT scan of the head • Multidisciplinary meeting: neurologist, geriatrician, neuropsychologist
Methods • Diagnosis – Subjective cognitive impairment (SCI) – Mild cognitive impairment (MCI) – Alzheimer dementia (AD) – Vascular dementia (VaD) – Other dementia (incl. FTD, PD, LBD) – Other diagnosis (a neurologic or psychiatric disorder)
Methods
Statistics • Logistic regression analysis – Age/sex adjusted – Adjusted for age, sex, hypertension, diabetes mellitus, hyperlipidemia, smoking • Linear regression analysis – Age/sex adjusted – Adjusted for age, sex and education level
Patient characteristics Total, HCC present, HCC absent, P-value Characteristic n= 1991 (100%) n= 380 (19.1%) n= 1611 (80.9%) Age, median (yrs) 80 81 79 <0.01 Gender, male % 40.3 43.2 39.6 0.22 Education level, mean 4.34 4.20 4.37 0.05 Cerebral infarct % 5.2 3.4 5.6 0.10 TIA, % 5.8 6.6 5.6 0.47 Hypertension % 33.9 33.9 33.9 1.00 Diabetes mellitus % 15.9 20.8 14.8 0.01 Hyperlipidaemia % 7.7 7.1 7.8 0.75 Smoking % Current 11.5 13.4 11.0 0.39 Former 22.8 22.9 22.8 Never 65.6 63.7 66.1
Patient characteristics Total, HCC present, HCC absent, P-value Characteristic n= 1991 (100%) n= 380 (19.1%) n= 1611 (80.9%) Age, median (yrs) 80 81 79 <0.01 Gender, male % 40.3 43.2 39.6 0.22 Education level, mean 4.34 4.20 4.37 0.05 Cerebral infarct % 5.2 3.4 5.6 0.10 TIA, % 5.8 6.6 5.6 0.47 Hypertension % 33.9 33.9 33.9 1.00 Diabetes mellitus % 15.9 20.8 14.8 0.01 Hyperlipidaemia % 7.7 7.1 7.8 0.75 Smoking % Current 11.5 13.4 11.0 0.39 Former 22.8 22.9 22.8 Never 65.6 63.7 66.1
Patient characteristics Total, HCC present, HCC absent, P-value Characteristic n= 1991 (100%) n= 380 (19.1%) n= 1611 (80.9%) Age, median (yrs) 80 81 79 <0.01 Gender, male % 40.3 43.2 39.6 0.22 Education level, mean 4.34 4.20 4.37 0.05 Cerebral infarct % 5.2 3.4 5.6 0.10 TIA, % 5.8 6.6 5.6 0.47 Hypertension % 33.9 33.9 33.9 1.00 Diabetes mellitus % 15.9 20.8 14.8 0.01 Hyperlipidaemia % 7.7 7.1 7.8 0.75 Smoking % Current 11.5 13.4 11.0 0.39 Former 22.8 22.9 22.8 Never 65.6 63.7 66.1
Patient characteristics Total, HCC present, HCC absent, P-value Characteristic n= 1991 (100%) n= 380 (19.1%) n= 1611 (80.9%) MTA score, mean 1.6 1.8 1.6 <0.01 Fazekas score, mean 1.0 1.1 1.0 0.54 Diagnosis % SCI 16.7 14.5 17.2 0.22 MCI 24.6 23.9 24.8 0.79 AD 41.6 45.5 40.7 0.09 VaD 2.8 2.9 2.8 0.86 Other dementia 2.7 1.8 2.9 0.37 Other diagnosis 11.6 11.3 11.7 0.93 MMSE, median 23 22 23 0.39 CAMCOG, median 76 75 76 0.04
Patient characteristics Total, HCC present, HCC absent, P-value Characteristic n= 1991 (100%) n= 380 (19.1%) n= 1611 (80.9%) MTA score, mean 1.6 1.8 1.6 <0.01 Fazekas score, mean 1.0 1.1 1.0 0.54 Diagnosis % SCI 16.7 14.5 17.2 0.22 MCI 24.6 23.9 24.8 0.79 AD 41.6 45.5 40.7 0.09 VaD 2.8 2.9 2.8 0.86 Other dementia 2.7 1.8 2.9 0.37 Other diagnosis 11.6 11.3 11.7 0.93 MMSE, median 23 22 23 0.39 CAMCOG, median 76 75 76 0.04
Risk factors for presence of HCC Univariable model Age/sex adjusted model Multivariable model Risk factors OR CI P OR CI P OR CI P Age 1.04 1.03-1.06 <0.01 1.05 1.03-1.06 <0.01 1.05 1.03-1.07 <0.01 Gender 0.86 0.69-1.08 0.20 0.78 0.62-0.98 0.03 0.81 0.64-1.03 0.08 Hypertension 1.00 0.79-1.27 0.98 0.95 0.75-1.21 0.68 0.91 0.71-1.17 0.46 Diabetes Mellitus 1.51 1.14-2.01 <0.01 1.47 1.10-1.95 <0.01 1.49 1.12-2.00 <0.01 Smoking* Current 1.27 0.90-1.78 0.17 1.51 1.06-2.16 0.02 1.50 1.05-2.14 0.03 Former 1.04 0.80-1.37 0.76 1.04 0.78-1.38 0.79 1.03 0.78-1.40 0.84 Hyperlipidaemia 0.90 0.59-1.39 0.64 0.91 0.59-1.41 0.67 0.89 0.57-1.39 0.60 * Smoking: compared with never smoked
Risk factors for presence of HCC Univariable model Age/sex adjusted model Multivariable model Risk factors OR CI P OR CI P OR CI P Age 1.04 1.03-1.06 <0.01 1.05 1.03-1.06 <0.01 1.05 1.03-1.07 <0.01 Gender 0.86 0.69-1.08 0.20 0.78 0.62-0.98 0.03 0.81 0.64-1.03 0.08 Hypertension 1.00 0.79-1.27 0.98 0.95 0.75-1.21 0.68 0.91 0.71-1.17 0.46 Diabetes Mellitus 1.51 1.14-2.01 <0.01 1.47 1.10-1.95 <0.01 1.49 1.12-2.00 <0.01 Smoking* Current 1.27 0.90-1.78 0.17 1.51 1.06-2.16 0.02 1.50 1.05-2.14 0.03 Former 1.04 0.80-1.37 0.76 1.04 0.78-1.38 0.79 1.03 0.78-1.40 0.84 Hyperlipidaemia 0.90 0.59-1.39 0.64 0.91 0.59-1.41 0.67 0.89 0.57-1.39 0.60 * Smoking: compared with never smoked
Association between HCC and cognition Univariable model Age/sex adjusted model Multivariable model Cognitive tests Beta CI P Beta CI P Beta CI P CAMCOG -1.40 -3.28-0.48 0.14 0.30 -1.48-2.07 0.74 0.86 -0.81-2.53 0.32 VAT -0.66 -1.15- -0.17 <0.01 -0.19 -0.65-0.27 0.43 -0.12 -0.57-0.34 0.62 MMSE -0.19 -0.82-0.45 0.56 0.38 -0.23-0.98 0.22 0.54 -0.04-1.12 0.07 CDT -0.06 -0.17-0.04 0.19 0.02 -0.08-0.12 0.95 0.04 -0.06-0.14 0.45
Conclusion • Increasing age, diabetes mellitus and current smoking were associated with hippocampal calcifications • No association of hippocampal calcifications with cognition
Questions?
Thank you! My colleagues: Remko Kockelkoren 2 MD Jules J. Claus 3 MD PhD Annemarieke de Jonghe 4 MD PhD Mirjam I. Geerlings 5 PhD Thomas E.F. Jongsma 6 MD Willem P.Th.M. Mali 2 MD PhD Jeroen Hendrikse 2 MD PhD Pim A. de Jong 2 MD PhD Huiberdina L. Koek 1 MD PhD 1 Department of Geriatrics, University Medical Center, Utrecht, The Netherlands 2 Department of Radiology, University Medical Center, Utrecht, The Netherlands 3 Department of Neurology, Tergooi hospital, Hilversum, The Netherlands 4 Department of Geriatrics, Tergooi hospital, Hilversum, The Netherlands 5 Julius Center for Health Sciences and Primary Care, Department of Epidemiology, University Medical Center, Utrecht, The Netherlands 6 Department of Radiology, Tergooi hospital, Hilversum, The Netherlands
Risk factors for presence of HCC Univariable analysis Age/sex adjusted analysis Multivariable analysis Model 1 Model 2 Model 3 OR CI P OR CI P OR CI P Risk factors <0.001 Age 1.04 1.03-1.06 <0.001 1.05 1.03-1.06 <0.001 1.05 1.03-1.07 Gender 0.86 0.69-1.08 0.204 0.78 0.62-0.98 0.032 0.81 0.64-1.03 0.083 Hypertension 1.00 0.79-1.27 0.984 0.95 0.75-1.21 0.681 0.91 0.71-1.17 0.464 Diabetes Mellitus 1.51 1.14-2.01 0.004 1.47 1.10-1.95 0.009 1.49 1.12-2.00 0.007 Smoking Never (ref) * * * * * * * * * Current 1.27 0.90-1.78 0.173 1.51 1.06-2.16 0.022 1.50 1.05-2.14 0.025 Former 1.04 0.80-1.37 0.760 1.04 0.78-1.38 0.788 1.03 0.78-1.40 0.835 Hyperlipidaemia 0.90 0.59-1.39 0.638 0.91 0.59-1.41 0.669 0.89 0.57-1.39 0.604 MTA score 1.23 1.10-1.38 <0.001 1.04 0.92-1.19 0.530 1.04 0.91-1.19 0.555 Fazekas score 1.08 0.95-1.23 0.222 0.93 0.81-1.07 0.292 0.92 0.80-1.06 0.250
Association between HCC and cognition measured by CAMCOG domains Univariable analysis Age/sex adjusted Multivariable adjusted Model 1 Model 2 Model 3 Cognitive tests Beta CI P Beta CI P Beta CI P CAMCOG TOTAL -1.40 -3.28-0.48 0.144 0.30 -1.48-2.07 0.743 0.86 -0.81-2.53 0.315 Orientation -0.16 -0.42-0.15 0.356 0.16 -0.11-0.43 0.249 0.21 -0.06-0.47 0.123 Memory -0.43 -1.07-0.20 0.178 0.08 -0.52-0.68 0.788 0.23 -0.35-0.81 0.435 Memory section -0.58 -1.45-0.29 0.191 0.22 -0.59-1.04 0.590 0.42 -0.37-1.21 0.295 Language -0.18 -0.61-0.25 0.412 0.05 -0.37-0.48 0.804 0.17 -0.23-0.58 0.397 Attention 0.04 -0.21-0.28 0.795 0.15 -0.10-0.39 0.238 0.19 -0.04-0.43 0.104 Praxis -0.18 -0.45-0.09 0.194 -0.01 -0.27-0.25 0.951 0.07 -0.19-0.32 0.610 Calculation -0.02 -0.08-0.04 0.506 0.01 -0.05-0.07 0.732 0.02 -0.04-0.08 0.547 Abstract reasoning -0.18 -0.45-0.10 0.205 -0.02 -0.29-0.25 0.874 0.05 -0.20-0.31 0.698 Perception -0.40 -0.60- -0.20 <0.001 -0.20 -0.39-0.01 0.035 -0.16 -0.35-0.02 0.084 Not memory section -0.85 -2.02-0.32 0.153 0.04 -1.08-1.17 0.941 0.40 -0.65-1.46 0.456
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