1
Journal of Alzheimer’s Disease xx (20xx) x–xx DOI 10.3233/JAD-150188 IOS Press
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4
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2
Gender-Specific Differences in Cognitive Profiles of Patients with Alzheimer’s Disease: Results of the Prospective Dementia Registry Austria (PRODEM-Austria)
or P
1
8
a Department
9
b Department
10 11 12 13
of Neurology, Medical University of Vienna, Austria of Medical Statistics and Informatics, Medical University of Vienna, Austria c Department of Neurology, Medical University of Innsbruck, Austria d Department of Psychiatry and Psychotherapy, Regional Hospital Hall in Tirol, Austria e Department of Neurology, General Hospital Linz, Austria f Department of Neurology, Division of Neurogeriatrics, Medical University of Graz, Austria
dA
6
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Gisela Pusswalda,∗ , Johann Lehrnera , Michael Hagmannb , Peter Dal-Biancoa , Thomas Benkec , Marisa Loitfelderf , Josef Marksteinerd , Jochen Mosbacherf , Gerhard Ransmayre , Guenter Saninc , Reinhold Schmidtf and PRODEM Study Group
5
cte
Accepted 11 March 2015
28
Keywords: Alzheimer’s dementia, Alzheimer’s disease, cognitive function, episodic memory, gender differences
17 18 19 20 21 22 23 24 25 26
co
16
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Abstract. Background: Alzheimer’s disease (AD) is one of the most common age-related diseases in the western world. Gender differences in neuropsychological functions are seldom evaluated in AD. Objective: Recent investigations suggested that gender may be an important modifying factor in the development and progression of AD. We examined gender-specific differences in the pattern of cognitive dysfunction of patients with mild to moderate AD. Methods: We examined 113 males (mean age 78) and 173 females (mean age 80) of the prospective registry on dementia in Austria (PRODEM). We analyzed differences in the cognitive profile between male and female AD patients on the CERAD-Plus test battery. Results: We found gender-related differences in the neuropsychological domains of verbal learning; the women tended to perform worse than men. Controlling for depression, stage and duration of dementia, and the level of education, there was still a significant effect of gender on verbal episodic memory. Conclusion: There is an interaction between gender and cognitive function, most notable in verbal episodic memory; female patients in the early stage of AD performed worse on verbal episodic memory than men. This indicates that the gender-specificities of neuropsychological functions should be given careful consideration in clinical diagnosis of dementia.
14
INTRODUCTION
∗ Correspondence
to: Gisela Pusswald, Medical University of Vienna, Department of Neurology, W¨ahringer G¨urtel 18-20, 1090 Vienna, Austria. Tel.: +43140400 57720; E-mail: [email protected].
Alzheimer’s disease (AD) is one of the most common age-related diseases in the western world. Gender differences in neuropsychological functions, which are well documented in non-demented people [1–5], are seldom evaluated in AD. In the non-demented population, on average, women outperform men in verbal
ISSN 1387-2877/15/$35.00 © 2015 – IOS Press and the authors. All rights reserved
29
30 31 32 33 34 35
2
G. Pusswald et al. / Gender-Specific Differences in Cognitive Profiles of AD Patients Table 1 Socio-demographic variables
Age, years (median, IQR) Living in partnership, n (%) Education, years (median, IQR) Duration of dementia, months (median, IQR) Total Mini-Mental State Exam scores (median IQR)
Male n = 113
Female n = 173
Significance
78 (73–83) 85.8 9 (9–13) 24 (12–40) 23 (19–25)
80 (73.25–85) 49.2 8 (8–12) 24 (12–39.5) 22 (19–25)
z = 1.06 p = 0.28 z = −4.78 p = 0.00∗ z = −4.67 p = 0.00∗ z = −0.31 p = 0.751 z = −0.809 p = 0.419
roo f
Probable Alzheimer’s Disease
∗ p < 0.05; ∗∗ p < 0.005.
43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66
67
68 69
70 71 72 73 74
or P
42
uth
41
diagnosis according to DSM-IV criteria [19], noninstitutionalization, no need for 24-h care, and availability of a caregiver who agrees to provide information on the patients’ and his/her own condition. Patients were excluded from the study if they were unable to sign an informed consent or if “co-morbidities” (life-threatening disease and severe dementia) leading to a premature termination of the study were present. The study centers were situated in six of nine provinces of the State of Austria with investigators representing the specialties of neurology and/or psychiatry. The baseline evaluation included patient and caregiver demographics, duration of dementia symptoms, assessment of the patients’ living situation and resource utilization, presence of co-morbidities, and recording of anti-dementia and concomitant medication, as well as extensive clinical, cognitive, behavioral, and functional assessment. Biobanking including sampling of DNA, RNA, plasma, and serum was done. MRI scans were obtained according to standardized protocols. According to NINCDS-ADRDA criteria [20], 56.7% of study participants were diagnosed as probable and 25.4% as possible AD patients. The current study cohort consisted of those 286 participants, 113 men and 173 women, with a diagnosis of probable AD. The demographics of the cohort are described in Table 1.
dA
40
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39
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38
fluency and episodic memory tasks [6], while men obtain better scores on nonverbal visuospatial tasks [7–9]. Previous studies in AD patients found hardly any gender-specific differences when global performance measures were used for the assessment of cognitive impairment [10, 11]. By contrast, studies that applied complex neuropsychological test batteries showed that female AD patients were usually more impaired than males in tasks of naming [12] and episodic and semantic memory [12, 13], but also in tests assessing verbal fluency [14, 15]. It is widely unknown if these gender-specific differences in patterns of cognitive dysfunction are caused by differences in socio-demographic factors such as education or by differences in disease-related factors like disease duration and severity. Differences in the frequency of comorbidities among male and female AD patients might also be responsible [16–18]. The goal of this study was to investigate the gender-related differences in cognitive profiles of female and male patients with AD in a large sample of referrals to memory clinics in Austria. We studied the differences in cognitive performance between male and female AD patients according to their age and stage of dementia. Patients were from the Prospective Dementia Registry (PRODEM) Austria and all underwent an extensive, validated, and normed neuropsychological test battery. The possible influence of gender-specific differences in socio-demographic factors on the test performance of study participants was also investigated.
co
37
METHODS
Un
36
Subjects’ characteristics and recruitment procedure PRODEM Austria, the prospective registry on dementia in Austria, is an ongoing longitudinal multi-center cohort study conducted in 12 memory clinics in our country. Since 2009, 508 patients have been included. Inclusion criteria were dementia
Neuropsychological assessment For assessment of cognitive functioning, the “Consortium to Establish a Registry for Alzheimer’s disease (CERAD-Plus)” neuropsychological test battery was used [21, 22]. This battery consists of ten subtests: • Animal Category Naming Test for measurement of semantic language production and verbal fluency. Subjects are asked to name as many animals as possible in one minute. The total number of different animals named was scored. • Modified Boston Naming Test for detection of basic capacity of naming. Subjects are asked to
75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102
103
104 105 106 107
108 109 110 111 112 113 114
G. Pusswald et al. / Gender-Specific Differences in Cognitive Profiles of AD Patients
122 123 124
•
125 126 127 128 129
•
130 131 132 133 134 135
•
136 137 138 139 140 141 142 143
•
144 145 146
•
147 148 149 150 151
•
152 153 154 155 156 157 158 159 160 161 162 163 164 165
•
Statistical analysis
roo f
121
All analyses were carried out by using the Statistical Analysis software SAS. Descriptive statistics of sociodemographic characteristics and the CERAD-Plus z-values were expressed as median and interquartile ranges according to the distribution. We used Mann-Whitney-U Test to compare differences between female and male patients in age, duration of disease, years of education, and cognitive functions. Prior to analyzing the cognitive domains, we transformed the CERAD-Plus data in z-scores to equate the metric across dimensions of education, gender, and age. In order to compare cognitive functions between male and female patients, subgroups were built according to age and severity of dementia based on the MMSE. A multiple analysis of variances was calculated to examine the influence of education and living situation on cognitive variables. In order to control the statistical error of multiple comparisons the Bonferroni-Holm correction was applied. Spearman’s correlation calculation was used to determine the relationship between duration of disease and CERAD-Plus scores.
or P
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uth
•
dA
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• The Geriatric Depression Scale (GDS) [24] was used to assess depressive symptoms. The maximum score is 15. A score of 0 to 5 is normal and a score greater than 5 suggests depression.
cte
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117
name 15 presented line drawn objects in subsets of words used with high, medium, and low frequency of occurrence (three groups of five items). The maximum score is 15 points. Mini-Mental State Examination (MMSE), a cognitive screening to measure the severity of dementia, covering different cognitive domains, including orientation, memory, language, and praxis, scoring 30 points as maximum. World list memory test (WL), a free recall memory test for assessing the learning ability for new verbal information. On the first trial, the subject is asked to read 10 printed words presented at the rate of one every two seconds. World list recall (WLR): The subject is then asked to recall as many words as possible. On each of two subsequent trials, the 10 words are presented in a new random order and the subject tries to recall all 10. Maximum number of correct responses is 30 for the three trials. World list recognition (WLSav) for assessing the ability of verbal recognition and of identifying distractors (World list discrimination, World list intrusions): Recognition of the previously presented 10 words (Word List Memory) mixed with 10 distractor words. The maximum score is 20 (10 words correctly recognized, 10 words correctly rejected). Constructional praxis test for measurement of visuospatial and constructional abilities by copying drawings. Constructional praxis recall Test: The subject is asked to remember and draw the figures presented in the Constructional Praxis task. A maximum of 11 points could be assessed in both Constructional tasks. Phonemic verbal fluency test (S-Fluency) for measurement of phonemic language production by naming as many words beginning with the letter “s” that came to mind within one minute. Trail making test (TMT A&B): Part A is an assessment for the measurement of selective attention and visual scanning, by connecting a set of 25 dots as fast as possible. Assessing Part B the subject alternates between numbers and letters, a test to assess the sequencing and mental flexibility. Results for both TMT A and B are reported as the number of seconds required to complete the task and a score difference of the Trail Making Test A and B is calculated (about the psychometrics of CERAD-Plus see [23]).
co
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3
RESULTS The demographic characteristics of the study participants are shown in Table 1. On average, men were higher educated and more often lived in a partnership than women. The GDS score was not significantly different between men and women (2.68 ± 2.58 versus 2.58 ± 2.5, p = 0.791). Table 2 summarizes standardized adjusted means of cognitive outcome measures of the CERAD-Plus test battery of men and women. As can be seen from this table, women performed worse on all verbal tasks including WL, WLR, and WLSav. The gender differences on WL and WLR remained significant even after correction for multiple testing by the Bonferroni-Holm method. These different results were found in only one domain, the verbal memory task, a dissociation of deficits. Analysis of variances showed that worse performance of women in WL could neither be explained by their lower level of education (F = 0.71, p = 0.79 and F = 1.21, p = 0.272) nor by the differences in the
166 167 168 169
170
171 172 173 174 175 176 177 178 179 180 181 182 183 184 185 186 187 188 189 190 191 192
193
194 195 196 197 198 199 200 201 202 203 204 205 206 207 208 209 210 211 212 213
4
G. Pusswald et al. / Gender-Specific Differences in Cognitive Profiles of AD Patients Table 2 Gender-specific profile of the CERAD-Plus subtests
CERAD Subtests
Gender
p
Percentile 25
Percentile 75
Median
−1.48 −1.42 −3.20 −2.30 −2.00 −2.10 −0.68 −2.50 −2.07 −0.83 −1.40 −1.42
−2.39 −2.50 −4.32 −3.40 −2.60 −2.80 −2.00 −3.10 −2.90 −1.70 −2.90 −2.17
−0.90 −0.50 −2.10 −1.45 −1.30 −1.10 0.90 −1.40 −1.27 −0.07 −0.60 −0.75
−1.50 −1.20 −3.45 −3.10 −2.90 −2.60 −0.82 −2.11 −2.20 −0.70 −1.42 −1.50
Percentile 25
Percentile 75
−2.20 −2.30 −4.75 −4.20 −3.60 −3.20 −1.90 −2.60 −2.60 −1.60 −2.50 −2.05
−0.80 −0.10 −2.60 −2.50 −2.10 −1.50 1.20 −1.60 −1.50 −0.07 −0.70 −0.90
z-value
0 -0.5 -1 -1.5 -2 -2.5 -3 -3.5 -4
dA cte rre
216 217 218 219 220 221 222 223 224 225 226 227
living situation between women and men (F = 0.064; p = 0.992 and F = 0.97; p = 0.87). Figure 1 displays the differences between women and men on WL, WLR, and WLSav between patients with mild (MMSE >20) versus those with moderately severe (MMSE
Journal of Alzheimer’s Disease xx (20xx) x–xx DOI 10.3233/JAD-150188 IOS Press
3
4
roo f
2
Gender-Specific Differences in Cognitive Profiles of Patients with Alzheimer’s Disease: Results of the Prospective Dementia Registry Austria (PRODEM-Austria)
or P
1
8
a Department
9
b Department
10 11 12 13
of Neurology, Medical University of Vienna, Austria of Medical Statistics and Informatics, Medical University of Vienna, Austria c Department of Neurology, Medical University of Innsbruck, Austria d Department of Psychiatry and Psychotherapy, Regional Hospital Hall in Tirol, Austria e Department of Neurology, General Hospital Linz, Austria f Department of Neurology, Division of Neurogeriatrics, Medical University of Graz, Austria
dA
6
uth
7
Gisela Pusswalda,∗ , Johann Lehrnera , Michael Hagmannb , Peter Dal-Biancoa , Thomas Benkec , Marisa Loitfelderf , Josef Marksteinerd , Jochen Mosbacherf , Gerhard Ransmayre , Guenter Saninc , Reinhold Schmidtf and PRODEM Study Group
5
cte
Accepted 11 March 2015
28
Keywords: Alzheimer’s dementia, Alzheimer’s disease, cognitive function, episodic memory, gender differences
17 18 19 20 21 22 23 24 25 26
co
16
Un
15
rre
27
Abstract. Background: Alzheimer’s disease (AD) is one of the most common age-related diseases in the western world. Gender differences in neuropsychological functions are seldom evaluated in AD. Objective: Recent investigations suggested that gender may be an important modifying factor in the development and progression of AD. We examined gender-specific differences in the pattern of cognitive dysfunction of patients with mild to moderate AD. Methods: We examined 113 males (mean age 78) and 173 females (mean age 80) of the prospective registry on dementia in Austria (PRODEM). We analyzed differences in the cognitive profile between male and female AD patients on the CERAD-Plus test battery. Results: We found gender-related differences in the neuropsychological domains of verbal learning; the women tended to perform worse than men. Controlling for depression, stage and duration of dementia, and the level of education, there was still a significant effect of gender on verbal episodic memory. Conclusion: There is an interaction between gender and cognitive function, most notable in verbal episodic memory; female patients in the early stage of AD performed worse on verbal episodic memory than men. This indicates that the gender-specificities of neuropsychological functions should be given careful consideration in clinical diagnosis of dementia.
14
INTRODUCTION
∗ Correspondence
to: Gisela Pusswald, Medical University of Vienna, Department of Neurology, W¨ahringer G¨urtel 18-20, 1090 Vienna, Austria. Tel.: +43140400 57720; E-mail: [email protected].
Alzheimer’s disease (AD) is one of the most common age-related diseases in the western world. Gender differences in neuropsychological functions, which are well documented in non-demented people [1–5], are seldom evaluated in AD. In the non-demented population, on average, women outperform men in verbal
ISSN 1387-2877/15/$35.00 © 2015 – IOS Press and the authors. All rights reserved
29
30 31 32 33 34 35
2
G. Pusswald et al. / Gender-Specific Differences in Cognitive Profiles of AD Patients Table 1 Socio-demographic variables
Age, years (median, IQR) Living in partnership, n (%) Education, years (median, IQR) Duration of dementia, months (median, IQR) Total Mini-Mental State Exam scores (median IQR)
Male n = 113
Female n = 173
Significance
78 (73–83) 85.8 9 (9–13) 24 (12–40) 23 (19–25)
80 (73.25–85) 49.2 8 (8–12) 24 (12–39.5) 22 (19–25)
z = 1.06 p = 0.28 z = −4.78 p = 0.00∗ z = −4.67 p = 0.00∗ z = −0.31 p = 0.751 z = −0.809 p = 0.419
roo f
Probable Alzheimer’s Disease
∗ p < 0.05; ∗∗ p < 0.005.
43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66
67
68 69
70 71 72 73 74
or P
42
uth
41
diagnosis according to DSM-IV criteria [19], noninstitutionalization, no need for 24-h care, and availability of a caregiver who agrees to provide information on the patients’ and his/her own condition. Patients were excluded from the study if they were unable to sign an informed consent or if “co-morbidities” (life-threatening disease and severe dementia) leading to a premature termination of the study were present. The study centers were situated in six of nine provinces of the State of Austria with investigators representing the specialties of neurology and/or psychiatry. The baseline evaluation included patient and caregiver demographics, duration of dementia symptoms, assessment of the patients’ living situation and resource utilization, presence of co-morbidities, and recording of anti-dementia and concomitant medication, as well as extensive clinical, cognitive, behavioral, and functional assessment. Biobanking including sampling of DNA, RNA, plasma, and serum was done. MRI scans were obtained according to standardized protocols. According to NINCDS-ADRDA criteria [20], 56.7% of study participants were diagnosed as probable and 25.4% as possible AD patients. The current study cohort consisted of those 286 participants, 113 men and 173 women, with a diagnosis of probable AD. The demographics of the cohort are described in Table 1.
dA
40
cte
39
rre
38
fluency and episodic memory tasks [6], while men obtain better scores on nonverbal visuospatial tasks [7–9]. Previous studies in AD patients found hardly any gender-specific differences when global performance measures were used for the assessment of cognitive impairment [10, 11]. By contrast, studies that applied complex neuropsychological test batteries showed that female AD patients were usually more impaired than males in tasks of naming [12] and episodic and semantic memory [12, 13], but also in tests assessing verbal fluency [14, 15]. It is widely unknown if these gender-specific differences in patterns of cognitive dysfunction are caused by differences in socio-demographic factors such as education or by differences in disease-related factors like disease duration and severity. Differences in the frequency of comorbidities among male and female AD patients might also be responsible [16–18]. The goal of this study was to investigate the gender-related differences in cognitive profiles of female and male patients with AD in a large sample of referrals to memory clinics in Austria. We studied the differences in cognitive performance between male and female AD patients according to their age and stage of dementia. Patients were from the Prospective Dementia Registry (PRODEM) Austria and all underwent an extensive, validated, and normed neuropsychological test battery. The possible influence of gender-specific differences in socio-demographic factors on the test performance of study participants was also investigated.
co
37
METHODS
Un
36
Subjects’ characteristics and recruitment procedure PRODEM Austria, the prospective registry on dementia in Austria, is an ongoing longitudinal multi-center cohort study conducted in 12 memory clinics in our country. Since 2009, 508 patients have been included. Inclusion criteria were dementia
Neuropsychological assessment For assessment of cognitive functioning, the “Consortium to Establish a Registry for Alzheimer’s disease (CERAD-Plus)” neuropsychological test battery was used [21, 22]. This battery consists of ten subtests: • Animal Category Naming Test for measurement of semantic language production and verbal fluency. Subjects are asked to name as many animals as possible in one minute. The total number of different animals named was scored. • Modified Boston Naming Test for detection of basic capacity of naming. Subjects are asked to
75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102
103
104 105 106 107
108 109 110 111 112 113 114
G. Pusswald et al. / Gender-Specific Differences in Cognitive Profiles of AD Patients
122 123 124
•
125 126 127 128 129
•
130 131 132 133 134 135
•
136 137 138 139 140 141 142 143
•
144 145 146
•
147 148 149 150 151
•
152 153 154 155 156 157 158 159 160 161 162 163 164 165
•
Statistical analysis
roo f
121
All analyses were carried out by using the Statistical Analysis software SAS. Descriptive statistics of sociodemographic characteristics and the CERAD-Plus z-values were expressed as median and interquartile ranges according to the distribution. We used Mann-Whitney-U Test to compare differences between female and male patients in age, duration of disease, years of education, and cognitive functions. Prior to analyzing the cognitive domains, we transformed the CERAD-Plus data in z-scores to equate the metric across dimensions of education, gender, and age. In order to compare cognitive functions between male and female patients, subgroups were built according to age and severity of dementia based on the MMSE. A multiple analysis of variances was calculated to examine the influence of education and living situation on cognitive variables. In order to control the statistical error of multiple comparisons the Bonferroni-Holm correction was applied. Spearman’s correlation calculation was used to determine the relationship between duration of disease and CERAD-Plus scores.
or P
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uth
•
dA
119
• The Geriatric Depression Scale (GDS) [24] was used to assess depressive symptoms. The maximum score is 15. A score of 0 to 5 is normal and a score greater than 5 suggests depression.
cte
118
rre
117
name 15 presented line drawn objects in subsets of words used with high, medium, and low frequency of occurrence (three groups of five items). The maximum score is 15 points. Mini-Mental State Examination (MMSE), a cognitive screening to measure the severity of dementia, covering different cognitive domains, including orientation, memory, language, and praxis, scoring 30 points as maximum. World list memory test (WL), a free recall memory test for assessing the learning ability for new verbal information. On the first trial, the subject is asked to read 10 printed words presented at the rate of one every two seconds. World list recall (WLR): The subject is then asked to recall as many words as possible. On each of two subsequent trials, the 10 words are presented in a new random order and the subject tries to recall all 10. Maximum number of correct responses is 30 for the three trials. World list recognition (WLSav) for assessing the ability of verbal recognition and of identifying distractors (World list discrimination, World list intrusions): Recognition of the previously presented 10 words (Word List Memory) mixed with 10 distractor words. The maximum score is 20 (10 words correctly recognized, 10 words correctly rejected). Constructional praxis test for measurement of visuospatial and constructional abilities by copying drawings. Constructional praxis recall Test: The subject is asked to remember and draw the figures presented in the Constructional Praxis task. A maximum of 11 points could be assessed in both Constructional tasks. Phonemic verbal fluency test (S-Fluency) for measurement of phonemic language production by naming as many words beginning with the letter “s” that came to mind within one minute. Trail making test (TMT A&B): Part A is an assessment for the measurement of selective attention and visual scanning, by connecting a set of 25 dots as fast as possible. Assessing Part B the subject alternates between numbers and letters, a test to assess the sequencing and mental flexibility. Results for both TMT A and B are reported as the number of seconds required to complete the task and a score difference of the Trail Making Test A and B is calculated (about the psychometrics of CERAD-Plus see [23]).
co
116
Un
115
3
RESULTS The demographic characteristics of the study participants are shown in Table 1. On average, men were higher educated and more often lived in a partnership than women. The GDS score was not significantly different between men and women (2.68 ± 2.58 versus 2.58 ± 2.5, p = 0.791). Table 2 summarizes standardized adjusted means of cognitive outcome measures of the CERAD-Plus test battery of men and women. As can be seen from this table, women performed worse on all verbal tasks including WL, WLR, and WLSav. The gender differences on WL and WLR remained significant even after correction for multiple testing by the Bonferroni-Holm method. These different results were found in only one domain, the verbal memory task, a dissociation of deficits. Analysis of variances showed that worse performance of women in WL could neither be explained by their lower level of education (F = 0.71, p = 0.79 and F = 1.21, p = 0.272) nor by the differences in the
166 167 168 169
170
171 172 173 174 175 176 177 178 179 180 181 182 183 184 185 186 187 188 189 190 191 192
193
194 195 196 197 198 199 200 201 202 203 204 205 206 207 208 209 210 211 212 213
4
G. Pusswald et al. / Gender-Specific Differences in Cognitive Profiles of AD Patients Table 2 Gender-specific profile of the CERAD-Plus subtests
CERAD Subtests
Gender
p
Percentile 25
Percentile 75
Median
−1.48 −1.42 −3.20 −2.30 −2.00 −2.10 −0.68 −2.50 −2.07 −0.83 −1.40 −1.42
−2.39 −2.50 −4.32 −3.40 −2.60 −2.80 −2.00 −3.10 −2.90 −1.70 −2.90 −2.17
−0.90 −0.50 −2.10 −1.45 −1.30 −1.10 0.90 −1.40 −1.27 −0.07 −0.60 −0.75
−1.50 −1.20 −3.45 −3.10 −2.90 −2.60 −0.82 −2.11 −2.20 −0.70 −1.42 −1.50
Percentile 25
Percentile 75
−2.20 −2.30 −4.75 −4.20 −3.60 −3.20 −1.90 −2.60 −2.60 −1.60 −2.50 −2.05
−0.80 −0.10 −2.60 −2.50 −2.10 −1.50 1.20 −1.60 −1.50 −0.07 −0.70 −0.90
z-value
0 -0.5 -1 -1.5 -2 -2.5 -3 -3.5 -4
dA cte rre
216 217 218 219 220 221 222 223 224 225 226 227
living situation between women and men (F = 0.064; p = 0.992 and F = 0.97; p = 0.87). Figure 1 displays the differences between women and men on WL, WLR, and WLSav between patients with mild (MMSE >20) versus those with moderately severe (MMSE
