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Dementia observed 30 days after stroke
P734
Oral Sessions: O5-03: Genetics of Alzheimer’s Disease and Non-Alzheimer’s Disease Dementia
Table 4 Multivariate Logistic Regression Evaluating the Association between Pathologic Measures of Cerebrovascular Disease and Cerebral Infarction (N¼163) 1 MICRO 2
LACUNAR 3
CYSTIC 4
Neuropathology Variables
OR (95%CI)
P-value
OR (95%CI)
P-value
OR (95%CI)
P-value
Atherosclerosis (ATHERO) (0-3) Arteriolosclerosis (ARTERIO) (0-3) Amyloid angiopathy (CAA) (0-4) Apolipoprotein E4 (yes/no)
2.32 (1.21, 4.43) 1.1 (0.55, 2.18) 1.28 (0.85, 1.92) 0.5 (0.2, 1.21)
0.01 0.79 0.24 0.12
1.39 (0.72, 2.66) 1.99 (0.95, 4.17) 0.47 (0.27, 0.84) 0.92 (0.36, 2.34)
0.32 0.07 0.01 0.86
2.04 (1.002, 4.17) 1.17 (0.54, 2.54) 0.63 (0.38, 1.06) 1.65 (0.64, 4.28)
0.049 0.69 0.08 0.3
1. All models were adjusted for age at death, gender, ethnicity, and years of education 2. MICRO ¼ 0 (n ¼ 97), and MICRO>0 (n ¼ 66, range from 4.2 to 41.7) 3. LACUNAR ¼ 0 (n ¼ 117) , and LACUNAR>0 (n ¼ 46, range from 8.3 to 75) 4. CYSTIC ¼ 0 (n ¼ 126), and CYSTIC>0 (n ¼ 37, range from 5.6 to 83.3) ARTERIO ¼ arteriolosclerosis score; ATHERO ¼ atherosclerosis score; CVDPS ¼ cerebrovascular disease parenchymal pathology scores; CAA ¼ cerebral amyloid angiopathy; MICRO ¼ micro infarct; LACUNAR ¼ lacunar infarct; CYSTIC ¼ cystic infarct.
hypertensive from CAA-related encephalopathy. Microinfarcts, which have been correlated in the literature with severity of cognitive impairment, were most strongly associated with atherosclerosis, possibly resulting from artery to artery emboli.
O5-02-06
(1.29-2.45), 0.58 (0.48-0.72), 0.36 (0.29-0.43) in CH, and 1.76 (1.22-2.53), 5.53 (3.76-8.14), 3.39 (2.20-5.24), 1.95 (0.92-4.12), 1.61 (0.80-3.23), 1.04 (0.59-1.83), 2.43 (1.15-5.16), 2.43 (1.15-5.16), 0.67 (0.46-0.98), and 0.61 (0.42-0.88) in SAH. Conclusions: Dementia was most frequently observed after CH. Dementia within 30 days after stroke was associated with age, sex, systolic diastolic blood pressure, consciousness disturbance, paresis, and arrhythmia at the onset of stroke.
DEMENTIA OBSERVED 30 DAYS AFTER STROKE
Kazuo Shigematsu1, Hiromi Nakano2, Yoshiyuki Watanabe3, Tatsuyuki Sekimoto4, Kouichiro Shimizu5, Akihiko Nishizawa6, Masahiro Makino3, Atsushi Okumura7, Nobuo Takezawa8, Touru Seki9, Yasushi Kitagawa10, 1National Hospital Organization, Minami Kyoto Hospital, Kyoto, Japan; 2Kyoto Kizugawa Hospital, Joyo, Japan; 3Kyoto Prefectural University of Medicine, Kyoto, Japan; 4Kyoto Yosanoumi Hospital, Kyoto, Japan; 5Kyoto Fushimi Shimizu Hospital, Kyoto, Japan; 6 Nishizawa Hospital, Kyoto, Japan; 7Jujyo Rehabilitation Hospital, Kyoto, Japan; 8Kyoto Prefectural Support Center of Rehabilitation, Kyoto, Japan; 9 Seki Hospital, Kyoto, Japan; 10Kitagawa Hospital, Kyoto, Japan. Background: Two major causes of dementia are Alzheimer’s disease and vascular dementia. Vascular dementia is caused by various subtypes of cerebrovascular diseases, but investigations of dementia following three major subtypes, namely Cerebral Infarction (CI), Cerebral Hemorrhage (CH), and Subarachnoid Hemorrhage (SAH), should provide a better understanding of vascular dementia. Methods: The Kyoto Stroke Registry (KSR) registers newly developed stroke patients in Kyoto prefecture in Japan. The aim of this study is two folds: First, we examined the frequencies and degrees of dementia in 30 days after onset in each of the three major categories of strokes. Second, we investigated the relation between dementia and other characteristics, including risk factors, of the patients. Results: Of the 13,788 confirmed stroke events in the study cohort, 9011 (65.4%) were CI, 3549 (25.7%) were CH, and 1197 (8.7%) were SAH. Thirty-one (0.2%) of patients had a combination of stroke types. A total of 1454 patients died within a month. Mental functions were examined 30 days after the onset in 10,906 (79.1%) of patients. Dementia was confirmed in 27.5% (n ¼ 2102) of CI patients, in 38.2% (n ¼ 953) of CH patients, and in 26.0% (n ¼ 191) of SAH patients. Mean age, systolic blood pressure, and diastolic blood pressure in patients with/without dementia were 80.0/69.4 (P <0.05), 156.6/158.3, and 86.6/84.1in CI, 75.1/63.7, 172.9/169.9, and 92.4/94.1in CH, and 57.3/68.0, 163.4/153.5, and 89.3/85.7 in SAH. Odds ratios, and their 95% confidence intervals, of dementia in females vs. males, and for association with consciousness disturbance, paresis, arrhythmia, a history of diabetes mellitus, hyperlipemia or arrhythmia, tobacco usage, and alcohol usage were: 2.20 (1.98-2.43), 6.77 (6.04-7.59), 2.24 (1.97-2.55), 1.77 (1.56-2.01), 0.74 (0.65-0.83), 0.57 (0.51-0.65), 2.16 (1.92-2.43), 0.42 (0.37-0.47), and 0.34 (0.30-0.39) in CI,1.92 (1.63-2.26), 5.30(4.39-6.40), 1.22 (0.841.79), 2.68 (2.17-3.32), 1.35 (1.06-1.71), 0.88 (0.68-1.14), 1.76
ORAL SESSIONS: O5-03 GENETICS OF ALZHEIMER’S DISEASE AND NON-ALZHEIMER’S DISEASE DEMENTIA O5-03-01
DEEP RESEQUENCING OF 9 CONFIRMED LATE-ONSET ALZHEIMER’S DISEASE (LOAD) LOCI IDENTIFIES MULTIPLE GENOMIC REGIONS WITH POTENTIALLY FUNCTIONAL VARIANTS
Jonathan Haines1, Adam Naj2, Martin Kohli2, Kara Hamilton-Nelson3, Ruchita Rajbhandary3, Patrice L. Whitehead3, Regina Carney3, Elizabeth Crocco4, Clinton Wright5, Gary Beecham3, Eden Martin2, John Gilbert3, Stephan Zuchner3, Margaret Pericak-Vance2, Bonnie Levin5, 1 Vanderbilt University Medical Center, Nashville, Tennessee, United States; 2 University of Miami Hussman Institute for Human Genomics, Miami, Florida, United States; 3University of Miami, Miami, Florida, United States; 4Department of Psychiatry, University of Miami, Miami, Florida, United States; 5Department of Neurology, University of Miami, Miami, Florida, United States. Background: Besides APOE, recent genome-wide association studies (GWAS) have identified variants in nine genes (CR1, CLU, PICALM, BIN1, EPHA1, MS4A, CD33, CD2AP, and ABCA7) that confer LOAD risk. However, it is unclear if there are additional novel or rare variants in or near these genes that contribute to LOAD. We resequenced these genes and surrounding regions to identify functional polymorphisms in 291 LOAD cases and 103 cognitively normal controls. Methods: We performed targeted capture (NimbleGen SeqCap EZ probe libraries) and next-generation sequencing on Illumina’s HiSeq 2000. Target regions included variants in all LD blocks (r2>0.80) overlapping the nine genes, with an average span of 368.3 kilobases. We filtered variants on three criteria: (a) functionality (missense, nonsense, or splice-site variant), (b) potentially damaging effect as defined by Polyphen-2, and (c) presence in one or more cases and absence in controls. We also examined common and rare variants together grouping by gene and function and using set-based multilocus association testing (RVASSOC). Results: We identified 28,894 variants across the nine regions, out of which 21,203 were variants of minor allele frequency (MAF) <5% (19,100 with MAF <2%). 14,863 variants (51.4%) were
Oral Sessions: O5-03: Genetics of Alzheimer’s Disease and Non-Alzheimer’s Disease Dementia
Table 4 Multivariate Logistic Regression Evaluating the Association between Pathologic Measures of Cerebrovascular Disease and Cerebral Infarction (N¼163) 1 MICRO 2
LACUNAR 3
CYSTIC 4
Neuropathology Variables
OR (95%CI)
P-value
OR (95%CI)
P-value
OR (95%CI)
P-value
Atherosclerosis (ATHERO) (0-3) Arteriolosclerosis (ARTERIO) (0-3) Amyloid angiopathy (CAA) (0-4) Apolipoprotein E4 (yes/no)
2.32 (1.21, 4.43) 1.1 (0.55, 2.18) 1.28 (0.85, 1.92) 0.5 (0.2, 1.21)
0.01 0.79 0.24 0.12
1.39 (0.72, 2.66) 1.99 (0.95, 4.17) 0.47 (0.27, 0.84) 0.92 (0.36, 2.34)
0.32 0.07 0.01 0.86
2.04 (1.002, 4.17) 1.17 (0.54, 2.54) 0.63 (0.38, 1.06) 1.65 (0.64, 4.28)
0.049 0.69 0.08 0.3
1. All models were adjusted for age at death, gender, ethnicity, and years of education 2. MICRO ¼ 0 (n ¼ 97), and MICRO>0 (n ¼ 66, range from 4.2 to 41.7) 3. LACUNAR ¼ 0 (n ¼ 117) , and LACUNAR>0 (n ¼ 46, range from 8.3 to 75) 4. CYSTIC ¼ 0 (n ¼ 126), and CYSTIC>0 (n ¼ 37, range from 5.6 to 83.3) ARTERIO ¼ arteriolosclerosis score; ATHERO ¼ atherosclerosis score; CVDPS ¼ cerebrovascular disease parenchymal pathology scores; CAA ¼ cerebral amyloid angiopathy; MICRO ¼ micro infarct; LACUNAR ¼ lacunar infarct; CYSTIC ¼ cystic infarct.
hypertensive from CAA-related encephalopathy. Microinfarcts, which have been correlated in the literature with severity of cognitive impairment, were most strongly associated with atherosclerosis, possibly resulting from artery to artery emboli.
O5-02-06
(1.29-2.45), 0.58 (0.48-0.72), 0.36 (0.29-0.43) in CH, and 1.76 (1.22-2.53), 5.53 (3.76-8.14), 3.39 (2.20-5.24), 1.95 (0.92-4.12), 1.61 (0.80-3.23), 1.04 (0.59-1.83), 2.43 (1.15-5.16), 2.43 (1.15-5.16), 0.67 (0.46-0.98), and 0.61 (0.42-0.88) in SAH. Conclusions: Dementia was most frequently observed after CH. Dementia within 30 days after stroke was associated with age, sex, systolic diastolic blood pressure, consciousness disturbance, paresis, and arrhythmia at the onset of stroke.
DEMENTIA OBSERVED 30 DAYS AFTER STROKE
Kazuo Shigematsu1, Hiromi Nakano2, Yoshiyuki Watanabe3, Tatsuyuki Sekimoto4, Kouichiro Shimizu5, Akihiko Nishizawa6, Masahiro Makino3, Atsushi Okumura7, Nobuo Takezawa8, Touru Seki9, Yasushi Kitagawa10, 1National Hospital Organization, Minami Kyoto Hospital, Kyoto, Japan; 2Kyoto Kizugawa Hospital, Joyo, Japan; 3Kyoto Prefectural University of Medicine, Kyoto, Japan; 4Kyoto Yosanoumi Hospital, Kyoto, Japan; 5Kyoto Fushimi Shimizu Hospital, Kyoto, Japan; 6 Nishizawa Hospital, Kyoto, Japan; 7Jujyo Rehabilitation Hospital, Kyoto, Japan; 8Kyoto Prefectural Support Center of Rehabilitation, Kyoto, Japan; 9 Seki Hospital, Kyoto, Japan; 10Kitagawa Hospital, Kyoto, Japan. Background: Two major causes of dementia are Alzheimer’s disease and vascular dementia. Vascular dementia is caused by various subtypes of cerebrovascular diseases, but investigations of dementia following three major subtypes, namely Cerebral Infarction (CI), Cerebral Hemorrhage (CH), and Subarachnoid Hemorrhage (SAH), should provide a better understanding of vascular dementia. Methods: The Kyoto Stroke Registry (KSR) registers newly developed stroke patients in Kyoto prefecture in Japan. The aim of this study is two folds: First, we examined the frequencies and degrees of dementia in 30 days after onset in each of the three major categories of strokes. Second, we investigated the relation between dementia and other characteristics, including risk factors, of the patients. Results: Of the 13,788 confirmed stroke events in the study cohort, 9011 (65.4%) were CI, 3549 (25.7%) were CH, and 1197 (8.7%) were SAH. Thirty-one (0.2%) of patients had a combination of stroke types. A total of 1454 patients died within a month. Mental functions were examined 30 days after the onset in 10,906 (79.1%) of patients. Dementia was confirmed in 27.5% (n ¼ 2102) of CI patients, in 38.2% (n ¼ 953) of CH patients, and in 26.0% (n ¼ 191) of SAH patients. Mean age, systolic blood pressure, and diastolic blood pressure in patients with/without dementia were 80.0/69.4 (P <0.05), 156.6/158.3, and 86.6/84.1in CI, 75.1/63.7, 172.9/169.9, and 92.4/94.1in CH, and 57.3/68.0, 163.4/153.5, and 89.3/85.7 in SAH. Odds ratios, and their 95% confidence intervals, of dementia in females vs. males, and for association with consciousness disturbance, paresis, arrhythmia, a history of diabetes mellitus, hyperlipemia or arrhythmia, tobacco usage, and alcohol usage were: 2.20 (1.98-2.43), 6.77 (6.04-7.59), 2.24 (1.97-2.55), 1.77 (1.56-2.01), 0.74 (0.65-0.83), 0.57 (0.51-0.65), 2.16 (1.92-2.43), 0.42 (0.37-0.47), and 0.34 (0.30-0.39) in CI,1.92 (1.63-2.26), 5.30(4.39-6.40), 1.22 (0.841.79), 2.68 (2.17-3.32), 1.35 (1.06-1.71), 0.88 (0.68-1.14), 1.76
ORAL SESSIONS: O5-03 GENETICS OF ALZHEIMER’S DISEASE AND NON-ALZHEIMER’S DISEASE DEMENTIA O5-03-01
DEEP RESEQUENCING OF 9 CONFIRMED LATE-ONSET ALZHEIMER’S DISEASE (LOAD) LOCI IDENTIFIES MULTIPLE GENOMIC REGIONS WITH POTENTIALLY FUNCTIONAL VARIANTS
Jonathan Haines1, Adam Naj2, Martin Kohli2, Kara Hamilton-Nelson3, Ruchita Rajbhandary3, Patrice L. Whitehead3, Regina Carney3, Elizabeth Crocco4, Clinton Wright5, Gary Beecham3, Eden Martin2, John Gilbert3, Stephan Zuchner3, Margaret Pericak-Vance2, Bonnie Levin5, 1 Vanderbilt University Medical Center, Nashville, Tennessee, United States; 2 University of Miami Hussman Institute for Human Genomics, Miami, Florida, United States; 3University of Miami, Miami, Florida, United States; 4Department of Psychiatry, University of Miami, Miami, Florida, United States; 5Department of Neurology, University of Miami, Miami, Florida, United States. Background: Besides APOE, recent genome-wide association studies (GWAS) have identified variants in nine genes (CR1, CLU, PICALM, BIN1, EPHA1, MS4A, CD33, CD2AP, and ABCA7) that confer LOAD risk. However, it is unclear if there are additional novel or rare variants in or near these genes that contribute to LOAD. We resequenced these genes and surrounding regions to identify functional polymorphisms in 291 LOAD cases and 103 cognitively normal controls. Methods: We performed targeted capture (NimbleGen SeqCap EZ probe libraries) and next-generation sequencing on Illumina’s HiSeq 2000. Target regions included variants in all LD blocks (r2>0.80) overlapping the nine genes, with an average span of 368.3 kilobases. We filtered variants on three criteria: (a) functionality (missense, nonsense, or splice-site variant), (b) potentially damaging effect as defined by Polyphen-2, and (c) presence in one or more cases and absence in controls. We also examined common and rare variants together grouping by gene and function and using set-based multilocus association testing (RVASSOC). Results: We identified 28,894 variants across the nine regions, out of which 21,203 were variants of minor allele frequency (MAF) <5% (19,100 with MAF <2%). 14,863 variants (51.4%) were