Tatic hypotension (present), n ( ) CIRS score, median (IQR) No. of drugs, median (IQR) 76.9 (71?1) 139 (57) 24 (22?6) 49 (21) 109 (46) 21 (9) 93/153 (61) 33 (14) 111 (48) 12 (5) 90 (46) 6 (4?) 4 (2?) 76.1 (70?1), p = 0.502 51 (62), p = 0.256 24 (22.5?6), p = 0.217 15 (19), p = 0.704 30 (38), p = 0.115 9 (11), p = 0.495 31/53 (59), p = 0.803 8 (10), p = 0.302 37 (47), p = 0.862 2 (3), p = 0.227 35 (47), p = 0.945 6 (4?), p = 0.402 4 (2?), p = 0.159 41 (53), p = 0.167 p = 0.000 138 (56) 89 (36) 11 (4) 8 (3) 60 1676428 (73) 16 (20) 2 (2) 4 (5) 76.5 (71?1), p = 0.562 84 (60), p = 0.198 23.3 (22?5), p = 0.377 27 (21), p = 0.949 63 (47), p = 0.831 10 (7), p 
= 0.455 61/98 (62), p = 0.748 18 (14), p = 0.960 62 (48), p = 0.949 5 (4), p = 0.416 49 (44), p = 0.727 6 (4?), p = 0.780 4 (2?), p = 0.466 77 (57), p = 0.361 p = 0.002 89 (64) 38 (27) 5 (4) 7 (5)Missing data (out of n = 246) 0 0 5 16 11 12 93 14 16 22 49 10 11 9Blood pressure lowering medication*, n ( ) 141 (60) Dementia categories Alzheimer’s disease, n ( ) DLB/PDD, n ( ) Vascular dementia, n ( ) FTD/alcoholic dem., n ( )IQR = interquartile range; MMSE = Mini-Mental State Examination, 3-Amino-1-propanesulfonic acid normal range 24?0; AD = Alzheimer’s Disease; DLB = Dementia with Lewy Bodies; PDD = Parkinson’s Disease Dementia; VaD = vascular dementia; FTD = Frontotemporal Dementia; CIRS = Cumulative Illness Rating Scale, range 0 (no impairment)-52 (extremely severe impairment); APOE = Apolipoprotein E. *antianginals, MedChemExpress 4EGI-1 antihypertensives, tricyclic antidepressants, paroxetine,MAO inhibitors, dopamine agonists, diazepam, dipyridamole, phenothiazines, clozapine, quetiapine, haloperidol. Significant 1317923 results are shown in bold typeface. doi:10.1371/journal.pone.0052196.twhereas in our study only a minority (17 ) had clinically significant depression (defined as a Montgomery Asberg De-pression Rating Scale [40] score of at least 15). In the other studies [15,17], a majority of the relevant subjects had DLB, known toTable 2. Demographic and clinical characteristics, lowest vs. highest WMH quartile.Volumetry group OH (fractions) Systolic BP drop (median)* Diastolic BP drop (median)* Standing syst. BP#110 (fractions) Age (median)* Women (fractions) AD (fractions) Hypertension (fractions) Coronary heart disease (fractions) Diabetes mellitus (fractions) APOEe4 1 allele (fractions) Previous stroke (fractions) Smoker (former or present)(fractions) Heart failure (fractions) 10/17, 10/19 p = 0.970 10, 10 p = 0.949 0, 0 p = 0.308 1/17, 2/19 p = 1.000 73, 79.5 p = 0.081 15/20, 13/20 p = 0.730 16/20, 14/20 p = 0.715 6/18, 11/20 p = 0.310 1/19, 5/20 p = 0.182 1/19, 1/20 p = 1.000 11/12, 6/13 p = 0.030 2/20, 4/19 p = 0.407 8/20, 11/20 p = 0.527 0/20, 1/18 p = 0.Semi-quantitative group 12/25, 14/28 p = 1.000 10, 17.5 p = 0.492 3, 0 p = 0.158 4/26, 2/28 p = 0.413 72, 78.4 p = 0.002 19/37, 17/31 p = 0.966 22/37, 22/31 p = 0.463 10/36, 16/31 p = 0.081 6/35, 7/30 p = 0.756 3/36, 2/31 p = 1.000 17/36, 10/21 p = 0.353 2/34, 9/28 p = 0.016 19/33, 16/30 p = 0.933 2/34, 1/28 p = 1.WMH = white matter hyperintensities; OH = orthostatic hypotension; BP = blood pressure; 
AD = Alzheimer’s disease; APOE = apolipoprotein E. *Mann-Whitney U-test, all other comparisons Chi-Square or Fisher’s Exact test. Significant results are shown in bold typeface. doi:10.1371/journal.pone.0052196.tOH and WMH in Mild DementiaTable 3. Multiple logistic regression analysis of the effect of APOEe4 status on likelihood of having WMH volume in highest vs. lowest quartile (final model).T.Tatic hypotension (present), n ( ) CIRS score, median (IQR) No. of drugs, median (IQR) 76.9 (71?1) 139 (57) 24 (22?6) 49 (21) 109 (46) 21 (9) 93/153 (61) 33 (14) 111 (48) 12 (5) 90 (46) 6 (4?) 4 (2?) 76.1 (70?1), p = 0.502 51 (62), p = 0.256 24 (22.5?6), p = 0.217 15 (19), p = 0.704 30 (38), p = 0.115 9 (11), p = 0.495 31/53 (59), p = 0.803 8 (10), p = 0.302 37 (47), p = 0.862 2 (3), p = 0.227 35 (47), p = 0.945 6 (4?), p = 0.402 4 (2?), p = 0.159 41 (53), p = 0.167 p = 0.000 138 (56) 89 (36) 11 (4) 8 (3) 60 1676428 (73) 16 (20) 2 (2) 4 (5) 76.5 (71?1), p = 0.562 84 (60), p = 0.198 23.3 (22?5), p = 0.377 27 (21), p = 0.949 63 (47), p = 0.831 10 (7), p = 0.455 61/98 (62), p = 0.748 18 (14), p = 0.960 62 (48), p = 0.949 5 (4), p = 0.416 49 (44), p = 0.727 6 (4?), p = 0.780 4 (2?), p = 0.466 77 (57), p = 0.361 p = 0.002 89 (64) 38 (27) 5 (4) 7 (5)Missing data (out of n = 246) 0 0 5 16 11 12 93 14 16 22 49 10 11 9Blood pressure lowering medication*, n ( ) 141 (60) Dementia categories Alzheimer’s disease, n ( ) DLB/PDD, n ( ) Vascular dementia, n ( ) FTD/alcoholic dem., n ( )IQR = interquartile range; MMSE = Mini-Mental State Examination, normal range 24?0; AD = Alzheimer’s Disease; DLB = Dementia with Lewy Bodies; PDD = Parkinson’s Disease Dementia; VaD = vascular dementia; FTD = Frontotemporal Dementia; CIRS = Cumulative Illness Rating Scale, range 0 (no impairment)-52 (extremely severe impairment); APOE = Apolipoprotein E. *antianginals, antihypertensives, tricyclic antidepressants, paroxetine,MAO inhibitors, dopamine agonists, diazepam, dipyridamole, phenothiazines, clozapine, quetiapine, haloperidol. Significant 1317923 results are shown in bold typeface. doi:10.1371/journal.pone.0052196.twhereas in our study only a minority (17 ) had clinically significant depression (defined as a Montgomery Asberg De-pression Rating Scale [40] score of at least 15). In the other studies [15,17], a majority of the relevant subjects had DLB, known toTable 2. Demographic and clinical characteristics, lowest vs. highest WMH quartile.Volumetry group OH (fractions) Systolic BP drop (median)* Diastolic BP drop (median)* Standing syst. BP#110 (fractions) Age (median)* Women (fractions) AD (fractions) Hypertension (fractions) Coronary heart disease (fractions) Diabetes mellitus (fractions) APOEe4 1 allele (fractions) Previous stroke (fractions) Smoker (former or present)(fractions) Heart failure (fractions) 10/17, 10/19 p = 0.970 10, 10 p = 0.949 0, 0 p = 0.308 1/17, 2/19 p = 1.000 73, 79.5 p = 0.081 15/20, 13/20 p = 0.730 16/20, 14/20 p = 0.715 6/18, 11/20 p = 0.310 1/19, 5/20 p = 0.182 1/19, 1/20 p = 1.000 11/12, 6/13 p = 0.030 2/20, 4/19 p = 0.407 8/20, 11/20 p = 0.527 0/20, 1/18 p = 0.Semi-quantitative group 12/25, 14/28 p = 1.000 10, 17.5 p = 0.492 3, 0 p = 0.158 4/26, 2/28 p = 0.413 72, 78.4 p = 0.002 19/37, 17/31 p = 0.966 22/37, 22/31 p = 0.463 10/36, 16/31 p = 0.081 6/35, 7/30 p = 0.756 3/36, 2/31 p = 1.000 17/36, 10/21 p = 0.353 2/34, 9/28 p = 0.016 19/33, 16/30 p = 0.933 2/34, 1/28 p = 1.WMH = white matter hyperintensities; OH = orthostatic hypotension; BP = blood pressure; AD = Alzheimer’s disease; APOE = apolipoprotein E. *Mann-Whitney U-test, all other comparisons Chi-Square or Fisher’s Exact test. Significant results are shown in bold typeface. doi:10.1371/journal.pone.0052196.tOH and WMH in Mild DementiaTable 3. Multiple logistic regression analysis of the effect of APOEe4 status on likelihood of having WMH volume in highest vs. lowest quartile (final model).T.
