- Email: [email protected]
PREVALENCE, TOPOGRAPHY, AND RISK FACTORS OF CEREBRAL MICROBLEEDS IN DEMENTIA
Poster Presentations: IC-P
P67
German Center for Neurodegenerative Diseases, Rostock, Germany; 3 DZNE German Center for Neurodegenerative Diseases, Magdeburg, Germany; 4University of Magdeburg, Dept. of Neurology, Germany, Magdeburg, Germany; 5Otto-von-Guericke-University, Magdeburg, Germany; 6Otto-von-Guericke-University Magdeburg, Magdeburg, Germany; 7University Medicine Rostock and DZNE Rostock, Rostock, Germany. Contact e-mail: [email protected] Background: Amyotrophic lateral sclerosis (ALS) is a rare multi-system degenerative disease characterised by motor symptoms and, additionally, by cognitive impairments and behavioural abnormalities (Goldstein LH et al, 2013). So far, only a few imaging studies have explicitly related cognitive-behavioural symptoms to structural brain changes in ALS. The current study aimed to determine the association of cognitive-behavioural symptoms with the integrity of fiber tracts using DTI. We investigated a wide range of diffusion indices to comprehensively characterise the microstructural integrity of the white matter (Metwalli NS et al. 2010). Methods: We assessed 74 ALS patients and 65 matched healthy control subjects employing a comprehensive neuropsychological test battery and 3 Tesla-MRI. Using tract-based spatial statistics (TBSS), maps of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were compared among ALS patients with and without cognitive impairment and healthy controls. Statistical analysis was conducted using ANCOVAs. Further, a region of interest (ROI) approach was employed with a-priori defined white matter tracts based on the ICBM-DTI-81-WM labels atlas. The averaged diffusivity values of the ROIs were correlated with neuropsychological tests using linear regression. Results: Patients without cognitive impairment demonstrated white matter changes predominantly in motor tracts. Cognitively impaired patients (ca. 30%) presented, additionally, significant white matter alterations in extra-motor regions, particularly the frontal lobe areas (see figure 1). RD-maps, reflecting a loss of integrity of the axonal wall, revealed the most pronounced effects. Specific correlations between executive tasks, memory tasks, and behavioural measures were found with fiber tract integrity in the large association tracts. The majority of cognitive scores correlated with RD. Conclusions: Our findings indicate that white matter changes, predominantly in the long association fibre bundles, are related to disturbances of executive and memory functions. In particular, correlations between executive tasks and their functionally corresponding white matter structures suggest that cognitive impairment is related to structural white matter changes in ALS patients. Eventually, our study demonstrates that the integration of different DTI-metrics is useful investigating neurodegenerative disorders such ALS . Our results highlight radial diffusivity as the most sensitive marker of neurodegeneration in ALS, especially of extra-motor brain areas.
IC-P-120
Figure 1. Prevalence of CMBs depending on number of risk factors. Risk factors are: hypertension, hyperlipidemia, diabetes, male gender and high age defined as 65 years and above.
PREVALENCE, TOPOGRAPHY, AND RISK FACTORS OF CEREBRAL MICROBLEEDS IN DEMENTIA
Sara Shams1, Juha Martola2, Tobias Granberg3, Xiaozhen Li4, Mana Shams2, Mohammad Fereshtehnejad4, Lena Cavallin2, Peter Aspelin2, Maria Kristoffersen Wiberg2, Lars-Olof Wahlund4, 1 Karolinska Institute, Department of Clinical Science, Intervention and Technology (CLINTEC), Divisio, Solna, Sweden; 2Karolinska Institutet (KI), Department of Clinical Science, Intervention and Technology (CLINTEC), Division of Radiology, Stockholm, Sweden; 3Karolinska Institute, Department of Clinical Science, Intervention and Technology (CLINTEC), Division of Radiology, Stockholm, Sweden; 4Karolinska Institutet (KI), Department of Neurobiology, Care Sciences and Society (NVS), H1, Division of Clinical Geriatrics, Stockholm, Sweden. Contact e-mail: [email protected] Background: Cerebral microbleeds (CMBs) are histologically seen as minute hemosiderin deposits in the brain parenchyma, and on MRI,
SWI and T2* sequences, as round hypointense foci. CMBs develop due to two diseases common in a memory clinic: hypertension, causing CMBs in deep and infratentorial regions of the brain, and cerebral amyloid angiopathy, causing CMBs in lobar brain regions. Thus, by investigating the prevalence, topography, and risk factors of CMBs in dementia we aimed to obtain an insight in the disease mechanisms of different dementia diagnoses. Methods: In this prospective study we analysed consecutive patients with Alzheimer’s disease (n¼435), vascular dementia (n¼63), and mild (n¼439) and subjective (n¼403) cognitive impairment, undergoing dementia investigation at the memory clinic Karolinska University
P68
Poster Presentations: IC-P Hospital, Huddinge, 2006-2012. A total of 1340 patients (mean age 63 (610), 53% female) were recruited. All patients had an MRI of the brain, with SWI and/or T2* sequences, and the number and topography of CMBs were assessed. Clinical data was obtained from the dementia investigation. Results: Among the 1340 patients 22% had CMBs. Patients with CMBs had significantly higher age (P<0.001), were more frequently male (P<0.001), had lower cognitive score (P¼0.001), and had more often hyperlipidemia (P¼0.03) and hypertension (P<0.001). Subgroup analysis showed that hyperlipidemia and hypertension had significantly higher prevalence of CMBs only in mild and subjective cognitive impairment. Odds ratios for developing CMBs increased with the amount of risk factors (hypertension, hyperlipidemia, diabetes, male gender, and age 65 and over) in the whole group. Conclusions: Prevalence, topography, and risk factors of CMBs vary depending on dementia diagnosis and reflect the inherent pathology of different dementia diagnoses. Future studies should focus on further imaging and cerebrospinal fluid markers in relation to CMBs.
Figure 3. Odds Ratios of developing CMBs for number of risk factors. Risk factors are: hypertension, hyperlipidemia, diabetes, male gender and high age defined as 65 years and above. Patients with 0 risk factors are used as a reference. * P<0.05; ** P<0.001.
Table 1 The prevalence of CMBs in different dementia diagnoses
Patient Characteristics
All patients (n¼1340)
Subjective Cognitive Impairment (n¼403)
Alzheimer’s Disease (n¼435)
Mild cognitive Impairment (n¼439)
Vascular Dementia (n¼63)
CMB Prevalence, % (n) Odds Ratio (95% CI) Adjusted Odds Ratio (95% CI)
22 (289) -
11 (43) 1.0 (ref.) 1.0 (ref.)
28 (120) 3.1 (2.1-4.6)** 1.9 (1.2-3.0)*
21 (90) 2.1 (1.4-3.1) 1.4 (0.9-2.1)
57 (36) 10.9 (6.0-19.7)** 7.3 (3.7-14.5)**
Crude and adjusted odds ratios were performed with the subjective cognitive impairment group as reference. Odds ratios are adjusted for age, gender, hypertension, hyperlipidemia, and diabetes.*P<0$05;**P<0$001
Table 2 Impact of risk factors on CMB prevalence in different diagnostic groups. Prevalence of CMBs (%) (n) Diagnosis All Patients (n¼1340) Alzheimer’s Disease (n¼435)1 Mild cognitive impairment (n¼439) Subjective Cognitive Impairment (n¼403) Vascular Dementia (n¼63)
Hypertension
Hyperlipidemia
Diabetes
Male
+
-
+
-
+
-
+
-
28 (137)** 29 (45) 26 (49)* 19 (18)* 56 (25)
18 (151)** 27 (74) 17 (41)* 8 (25)* 61 (11)
25 (73)* 25.5 (25) 29 (27)* 18 (11)* 42 (10)
20 (215)* 28 (94) 18 (63)* 9 (32)* 67 (26)
25 (34) 31 (9) 22 (12) 12 (4) 50 (9)
21 (254) 27 (110) 20 (78) 11 (39) 60 (27)
28 (174)** 34 (68)* 26 (64)* 12 (17) 71 (25)*
16 (115)** 22 (52)* 13 (26)* 10 (26) 39 (11)*
* P<0.05; ** P<0.00001
Table 3 MMSE score and age in relation to CMBs.
Diagnosis All Patients (n¼1340) Alzheimer’s Disease (n¼435)1 Mild cognitive impairment (n¼439) Subjective Cognitive Impairment (n¼403) Vascular Dementia (n¼63) * P<0.05; ** P<0.001.
MMSE Score
Age
CMBs
CMBs
+
-
+
-
24(65)* 22 (65) 27 (63) 28 (64) 21 (66)
25(65)* 22 (65) 26 (64) 28 (63) 20 (64)
67 (68)** 70(68)* 66 (68)** 60 (68)* 65(69)
62 (610)** 67 (68)* 62 (69)** 57 (68)* 65 (613)
P67
German Center for Neurodegenerative Diseases, Rostock, Germany; 3 DZNE German Center for Neurodegenerative Diseases, Magdeburg, Germany; 4University of Magdeburg, Dept. of Neurology, Germany, Magdeburg, Germany; 5Otto-von-Guericke-University, Magdeburg, Germany; 6Otto-von-Guericke-University Magdeburg, Magdeburg, Germany; 7University Medicine Rostock and DZNE Rostock, Rostock, Germany. Contact e-mail: [email protected] Background: Amyotrophic lateral sclerosis (ALS) is a rare multi-system degenerative disease characterised by motor symptoms and, additionally, by cognitive impairments and behavioural abnormalities (Goldstein LH et al, 2013). So far, only a few imaging studies have explicitly related cognitive-behavioural symptoms to structural brain changes in ALS. The current study aimed to determine the association of cognitive-behavioural symptoms with the integrity of fiber tracts using DTI. We investigated a wide range of diffusion indices to comprehensively characterise the microstructural integrity of the white matter (Metwalli NS et al. 2010). Methods: We assessed 74 ALS patients and 65 matched healthy control subjects employing a comprehensive neuropsychological test battery and 3 Tesla-MRI. Using tract-based spatial statistics (TBSS), maps of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were compared among ALS patients with and without cognitive impairment and healthy controls. Statistical analysis was conducted using ANCOVAs. Further, a region of interest (ROI) approach was employed with a-priori defined white matter tracts based on the ICBM-DTI-81-WM labels atlas. The averaged diffusivity values of the ROIs were correlated with neuropsychological tests using linear regression. Results: Patients without cognitive impairment demonstrated white matter changes predominantly in motor tracts. Cognitively impaired patients (ca. 30%) presented, additionally, significant white matter alterations in extra-motor regions, particularly the frontal lobe areas (see figure 1). RD-maps, reflecting a loss of integrity of the axonal wall, revealed the most pronounced effects. Specific correlations between executive tasks, memory tasks, and behavioural measures were found with fiber tract integrity in the large association tracts. The majority of cognitive scores correlated with RD. Conclusions: Our findings indicate that white matter changes, predominantly in the long association fibre bundles, are related to disturbances of executive and memory functions. In particular, correlations between executive tasks and their functionally corresponding white matter structures suggest that cognitive impairment is related to structural white matter changes in ALS patients. Eventually, our study demonstrates that the integration of different DTI-metrics is useful investigating neurodegenerative disorders such ALS . Our results highlight radial diffusivity as the most sensitive marker of neurodegeneration in ALS, especially of extra-motor brain areas.
IC-P-120
Figure 1. Prevalence of CMBs depending on number of risk factors. Risk factors are: hypertension, hyperlipidemia, diabetes, male gender and high age defined as 65 years and above.
PREVALENCE, TOPOGRAPHY, AND RISK FACTORS OF CEREBRAL MICROBLEEDS IN DEMENTIA
Sara Shams1, Juha Martola2, Tobias Granberg3, Xiaozhen Li4, Mana Shams2, Mohammad Fereshtehnejad4, Lena Cavallin2, Peter Aspelin2, Maria Kristoffersen Wiberg2, Lars-Olof Wahlund4, 1 Karolinska Institute, Department of Clinical Science, Intervention and Technology (CLINTEC), Divisio, Solna, Sweden; 2Karolinska Institutet (KI), Department of Clinical Science, Intervention and Technology (CLINTEC), Division of Radiology, Stockholm, Sweden; 3Karolinska Institute, Department of Clinical Science, Intervention and Technology (CLINTEC), Division of Radiology, Stockholm, Sweden; 4Karolinska Institutet (KI), Department of Neurobiology, Care Sciences and Society (NVS), H1, Division of Clinical Geriatrics, Stockholm, Sweden. Contact e-mail: [email protected] Background: Cerebral microbleeds (CMBs) are histologically seen as minute hemosiderin deposits in the brain parenchyma, and on MRI,
SWI and T2* sequences, as round hypointense foci. CMBs develop due to two diseases common in a memory clinic: hypertension, causing CMBs in deep and infratentorial regions of the brain, and cerebral amyloid angiopathy, causing CMBs in lobar brain regions. Thus, by investigating the prevalence, topography, and risk factors of CMBs in dementia we aimed to obtain an insight in the disease mechanisms of different dementia diagnoses. Methods: In this prospective study we analysed consecutive patients with Alzheimer’s disease (n¼435), vascular dementia (n¼63), and mild (n¼439) and subjective (n¼403) cognitive impairment, undergoing dementia investigation at the memory clinic Karolinska University
P68
Poster Presentations: IC-P Hospital, Huddinge, 2006-2012. A total of 1340 patients (mean age 63 (610), 53% female) were recruited. All patients had an MRI of the brain, with SWI and/or T2* sequences, and the number and topography of CMBs were assessed. Clinical data was obtained from the dementia investigation. Results: Among the 1340 patients 22% had CMBs. Patients with CMBs had significantly higher age (P<0.001), were more frequently male (P<0.001), had lower cognitive score (P¼0.001), and had more often hyperlipidemia (P¼0.03) and hypertension (P<0.001). Subgroup analysis showed that hyperlipidemia and hypertension had significantly higher prevalence of CMBs only in mild and subjective cognitive impairment. Odds ratios for developing CMBs increased with the amount of risk factors (hypertension, hyperlipidemia, diabetes, male gender, and age 65 and over) in the whole group. Conclusions: Prevalence, topography, and risk factors of CMBs vary depending on dementia diagnosis and reflect the inherent pathology of different dementia diagnoses. Future studies should focus on further imaging and cerebrospinal fluid markers in relation to CMBs.
Figure 3. Odds Ratios of developing CMBs for number of risk factors. Risk factors are: hypertension, hyperlipidemia, diabetes, male gender and high age defined as 65 years and above. Patients with 0 risk factors are used as a reference. * P<0.05; ** P<0.001.
Table 1 The prevalence of CMBs in different dementia diagnoses
Patient Characteristics
All patients (n¼1340)
Subjective Cognitive Impairment (n¼403)
Alzheimer’s Disease (n¼435)
Mild cognitive Impairment (n¼439)
Vascular Dementia (n¼63)
CMB Prevalence, % (n) Odds Ratio (95% CI) Adjusted Odds Ratio (95% CI)
22 (289) -
11 (43) 1.0 (ref.) 1.0 (ref.)
28 (120) 3.1 (2.1-4.6)** 1.9 (1.2-3.0)*
21 (90) 2.1 (1.4-3.1) 1.4 (0.9-2.1)
57 (36) 10.9 (6.0-19.7)** 7.3 (3.7-14.5)**
Crude and adjusted odds ratios were performed with the subjective cognitive impairment group as reference. Odds ratios are adjusted for age, gender, hypertension, hyperlipidemia, and diabetes.*P<0$05;**P<0$001
Table 2 Impact of risk factors on CMB prevalence in different diagnostic groups. Prevalence of CMBs (%) (n) Diagnosis All Patients (n¼1340) Alzheimer’s Disease (n¼435)1 Mild cognitive impairment (n¼439) Subjective Cognitive Impairment (n¼403) Vascular Dementia (n¼63)
Hypertension
Hyperlipidemia
Diabetes
Male
+
-
+
-
+
-
+
-
28 (137)** 29 (45) 26 (49)* 19 (18)* 56 (25)
18 (151)** 27 (74) 17 (41)* 8 (25)* 61 (11)
25 (73)* 25.5 (25) 29 (27)* 18 (11)* 42 (10)
20 (215)* 28 (94) 18 (63)* 9 (32)* 67 (26)
25 (34) 31 (9) 22 (12) 12 (4) 50 (9)
21 (254) 27 (110) 20 (78) 11 (39) 60 (27)
28 (174)** 34 (68)* 26 (64)* 12 (17) 71 (25)*
16 (115)** 22 (52)* 13 (26)* 10 (26) 39 (11)*
* P<0.05; ** P<0.00001
Table 3 MMSE score and age in relation to CMBs.
Diagnosis All Patients (n¼1340) Alzheimer’s Disease (n¼435)1 Mild cognitive impairment (n¼439) Subjective Cognitive Impairment (n¼403) Vascular Dementia (n¼63) * P<0.05; ** P<0.001.
MMSE Score
Age
CMBs
CMBs
+
-
+
-
24(65)* 22 (65) 27 (63) 28 (64) 21 (66)
25(65)* 22 (65) 26 (64) 28 (63) 20 (64)
67 (68)** 70(68)* 66 (68)** 60 (68)* 65(69)
62 (610)** 67 (68)* 62 (69)** 57 (68)* 65 (613)