Effect of Alzheimer's disease risk genes on trajectories of cognitive function in the Cardiovascular Health Study

The trajectory of cognitive decline in patients with late-onset Alzheimer's disease varies widely. Genetic variations in CLU, PICALM, and CR1 are associated with Alzheimer's disease, but it is unknown whether they exert their effects by altering cognitive trajectory in elderly individuals...

Celý popis

Uloženo v:
Podrobná bibliografie
Vydáno v:The American journal of psychiatry Ročník 169; číslo 9; s. 954
Hlavní autoři: Sweet, Robert A, Seltman, Howard, Emanuel, James E, Lopez, Oscar L, Becker, James T, Bis, Joshua C, Weamer, Elise A, DeMichele-Sweet, Mary Ann A, Kuller, Lewis H
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States 01.09.2012
Témata:
Age of Onset
Aged
Alleles
Alzheimer Disease - complications
Alzheimer Disease - genetics
Alzheimer Disease - psychology
Apolipoprotein E4 - genetics
Bayes Theorem
Clusterin - genetics
Cohort Studies
Dementia - complications
Dementia - genetics
Dementia - psychology
Disease Progression
Female
Genetic Predisposition to Disease - genetics
Humans
Male
Models, Psychological
Monomeric Clathrin Assembly Proteins - genetics
Polymorphism, Single Nucleotide - genetics
Receptors, Complement 3b - genetics
Risk Factors
ISSN:1535-7228, 1535-7228
On-line přístup:Zjistit podrobnosti o přístupu
Tagy: Přidat tag
Žádné tagy, Buďte první, kdo vytvoří štítek k tomuto záznamu!
Abstract The trajectory of cognitive decline in patients with late-onset Alzheimer's disease varies widely. Genetic variations in CLU, PICALM, and CR1 are associated with Alzheimer's disease, but it is unknown whether they exert their effects by altering cognitive trajectory in elderly individuals at risk for the disease. The authors developed a Bayesian model to fit cognitive trajectories in a cohort of elderly subjects and test for genetic effects. They first validated the model's ability to detect the previously established effects of APOE ε4 alleles on age at cognitive decline and of psychosis on the rate of cognitive decline in 802 subjects from the Cardiovascular Health Cognition Study who did not have dementia at study entry and developed incident dementia during follow-up. The authors then evaluated the effects of CLU, PICALM, and CR1 on age and rate of decline in 1,831 subjects who did not have dementia at study entry and then did or did not develop incident dementia by study's end. The model generated robust fits to the observed cognitive trajectory data, and validation analysis supported the model's utility. CLU and CR1 were associated with more rapid cognitive decline. PICALM was associated with an earlier age at midpoint of cognitive decline. Associations remained after accounting for the effects of APOE and demographic factors. Evaluation of cognitive trajectories provides a powerful approach to dissecting genetic effects on the processes leading to cognitive deterioration and Alzheimer's disease.
AbstractList The trajectory of cognitive decline in patients with late-onset Alzheimer's disease varies widely. Genetic variations in CLU, PICALM, and CR1 are associated with Alzheimer's disease, but it is unknown whether they exert their effects by altering cognitive trajectory in elderly individuals at risk for the disease.OBJECTIVEThe trajectory of cognitive decline in patients with late-onset Alzheimer's disease varies widely. Genetic variations in CLU, PICALM, and CR1 are associated with Alzheimer's disease, but it is unknown whether they exert their effects by altering cognitive trajectory in elderly individuals at risk for the disease.The authors developed a Bayesian model to fit cognitive trajectories in a cohort of elderly subjects and test for genetic effects. They first validated the model's ability to detect the previously established effects of APOE ε4 alleles on age at cognitive decline and of psychosis on the rate of cognitive decline in 802 subjects from the Cardiovascular Health Cognition Study who did not have dementia at study entry and developed incident dementia during follow-up. The authors then evaluated the effects of CLU, PICALM, and CR1 on age and rate of decline in 1,831 subjects who did not have dementia at study entry and then did or did not develop incident dementia by study's end.METHODThe authors developed a Bayesian model to fit cognitive trajectories in a cohort of elderly subjects and test for genetic effects. They first validated the model's ability to detect the previously established effects of APOE ε4 alleles on age at cognitive decline and of psychosis on the rate of cognitive decline in 802 subjects from the Cardiovascular Health Cognition Study who did not have dementia at study entry and developed incident dementia during follow-up. The authors then evaluated the effects of CLU, PICALM, and CR1 on age and rate of decline in 1,831 subjects who did not have dementia at study entry and then did or did not develop incident dementia by study's end.The model generated robust fits to the observed cognitive trajectory data, and validation analysis supported the model's utility. CLU and CR1 were associated with more rapid cognitive decline. PICALM was associated with an earlier age at midpoint of cognitive decline. Associations remained after accounting for the effects of APOE and demographic factors.RESULTSThe model generated robust fits to the observed cognitive trajectory data, and validation analysis supported the model's utility. CLU and CR1 were associated with more rapid cognitive decline. PICALM was associated with an earlier age at midpoint of cognitive decline. Associations remained after accounting for the effects of APOE and demographic factors.Evaluation of cognitive trajectories provides a powerful approach to dissecting genetic effects on the processes leading to cognitive deterioration and Alzheimer's disease.CONCLUSIONSEvaluation of cognitive trajectories provides a powerful approach to dissecting genetic effects on the processes leading to cognitive deterioration and Alzheimer's disease.
The trajectory of cognitive decline in patients with late-onset Alzheimer's disease varies widely. Genetic variations in CLU, PICALM, and CR1 are associated with Alzheimer's disease, but it is unknown whether they exert their effects by altering cognitive trajectory in elderly individuals at risk for the disease. The authors developed a Bayesian model to fit cognitive trajectories in a cohort of elderly subjects and test for genetic effects. They first validated the model's ability to detect the previously established effects of APOE ε4 alleles on age at cognitive decline and of psychosis on the rate of cognitive decline in 802 subjects from the Cardiovascular Health Cognition Study who did not have dementia at study entry and developed incident dementia during follow-up. The authors then evaluated the effects of CLU, PICALM, and CR1 on age and rate of decline in 1,831 subjects who did not have dementia at study entry and then did or did not develop incident dementia by study's end. The model generated robust fits to the observed cognitive trajectory data, and validation analysis supported the model's utility. CLU and CR1 were associated with more rapid cognitive decline. PICALM was associated with an earlier age at midpoint of cognitive decline. Associations remained after accounting for the effects of APOE and demographic factors. Evaluation of cognitive trajectories provides a powerful approach to dissecting genetic effects on the processes leading to cognitive deterioration and Alzheimer's disease.
Author Sweet, Robert A
Weamer, Elise A
Kuller, Lewis H
Seltman, Howard
Emanuel, James E
Lopez, Oscar L
Becker, James T
Bis, Joshua C
DeMichele-Sweet, Mary Ann A
Author_xml – sequence: 1
  givenname: Robert A
  surname: Sweet
  fullname: Sweet, Robert A
  email: sweetra@upmc.edu
  organization: Department of Psychiatry, University of Pittsburgh, Pittsburgh, USA. sweetra@upmc.edu
– sequence: 2
  givenname: Howard
  surname: Seltman
  fullname: Seltman, Howard
– sequence: 3
  givenname: James E
  surname: Emanuel
  fullname: Emanuel, James E
– sequence: 4
  givenname: Oscar L
  surname: Lopez
  fullname: Lopez, Oscar L
– sequence: 5
  givenname: James T
  surname: Becker
  fullname: Becker, James T
– sequence: 6
  givenname: Joshua C
  surname: Bis
  fullname: Bis, Joshua C
– sequence: 7
  givenname: Elise A
  surname: Weamer
  fullname: Weamer, Elise A
– sequence: 8
  givenname: Mary Ann A
  surname: DeMichele-Sweet
  fullname: DeMichele-Sweet, Mary Ann A
– sequence: 9
  givenname: Lewis H
  surname: Kuller
  fullname: Kuller, Lewis H
BackLink https://www.ncbi.nlm.nih.gov/pubmed/22952074$$D View this record in MEDLINE/PubMed
BookMark eNpN0E1PwzAMBuAIDbEP-AtTbnDpSJx26Y7TNBjSJA7AuUpTZ8vo15J00vj1FDEkfLFf65EPHpNB3dRIyJSzGedy_qja1s7UoZ0B49CvOPCUJ1dkxBORRBIgHfybh2Ts_YH1JSTckCHAIgEm4xE5ro1BHWhj6LL82qOt0N17WliPyiN11n_SHdboaVPT4NShx42zP9lQ3exqG-wJqelqHWxPbK_2SFfKFbY5Ka-7Ujm6QVWGPX0LXXG-JddGlR7vLn1CPp7W76tNtH19flktt5GK5SJESjNZSJMIlmiBqUIOKjWcFQhsbuJcgALN8lhIoeeQI0Ke5wmalJlCpAsDE_Lwe7d1zbFDH7LKeo1lqWpsOp9xJtJkAVKwnk4vtMsrLLLW2Uq5c_b3JvgGV7lv7Q
CitedBy_id crossref_primary_10_3389_fneur_2021_735036
crossref_primary_10_1016_j_exger_2020_110951
crossref_primary_10_3390_cells11243994
crossref_primary_10_1007_s12035_014_8878_3
crossref_primary_10_1038_mp_2015_62
crossref_primary_10_1002_ajmg_b_32509
crossref_primary_10_1016_j_neurobiolaging_2014_04_022
crossref_primary_10_1038_s41380_021_01152_8
crossref_primary_10_1016_j_anbehav_2014_06_013
crossref_primary_10_1016_j_neurobiolaging_2013_05_028
crossref_primary_10_1007_s12017_013_8225_2
crossref_primary_10_1111_jnc_12261
crossref_primary_10_3389_fnagi_2017_00055
crossref_primary_10_1186_s13195_018_0458_8
crossref_primary_10_2217_pgs_13_161
crossref_primary_10_1016_j_neurobiolaging_2015_08_006
crossref_primary_10_1007_s12035_015_9098_1
crossref_primary_10_1007_s00429_014_0738_4
crossref_primary_10_1016_j_trci_2017_03_004
crossref_primary_10_1016_j_biopsych_2013_08_020
crossref_primary_10_1007_s12031_016_0804_x
crossref_primary_10_1002_gps_4145
crossref_primary_10_3389_fnins_2020_00324
crossref_primary_10_1007_s13311_022_01185_z
crossref_primary_10_1007_s12035_014_8761_2
crossref_primary_10_1097_WAD_0000000000000137
crossref_primary_10_1007_s13206_015_9306_8
crossref_primary_10_1016_j_neurobiolaging_2014_07_042
crossref_primary_10_1002_sim_8100
crossref_primary_10_1038_mp_2017_81
crossref_primary_10_3233_JAD_190342
crossref_primary_10_1007_s12035_016_9886_2
crossref_primary_10_3389_fnins_2019_00164
crossref_primary_10_3233_JAD_201182
crossref_primary_10_3233_JAD_191214
crossref_primary_10_1016_j_dadm_2015_08_002
crossref_primary_10_1007_s12035_015_9343_7
crossref_primary_10_1016_j_euroneuro_2015_11_004
crossref_primary_10_1016_j_neurobiolaging_2014_03_003
crossref_primary_10_1007_s12035_016_0358_5
crossref_primary_10_2217_nmt_13_40
crossref_primary_10_1016_j_tins_2017_06_002
crossref_primary_10_1002_hbm_22494
crossref_primary_10_3389_fimmu_2019_02585
crossref_primary_10_1016_j_neuroscience_2014_09_061
crossref_primary_10_1002_gps_4326
crossref_primary_10_1016_j_arr_2016_02_002
crossref_primary_10_1007_s11064_020_03176_y
crossref_primary_10_3233_JAD_160774
crossref_primary_10_1016_j_jocn_2014_03_015
ContentType Journal Article
DBID CGR
CUY
CVF
ECM
EIF
NPM
7X8
DOI 10.1176/appi.ajp.2012.11121815
DatabaseName Medline
MEDLINE
MEDLINE (Ovid)
MEDLINE
MEDLINE
PubMed
MEDLINE - Academic
DatabaseTitle MEDLINE
Medline Complete
MEDLINE with Full Text
PubMed
MEDLINE (Ovid)
MEDLINE - Academic
DatabaseTitleList MEDLINE - Academic
MEDLINE
Database_xml – sequence: 1
  dbid: NPM
  name: PubMed
  url: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
  sourceTypes: Index Database
– sequence: 2
  dbid: 7X8
  name: MEDLINE - Academic
  url: https://search.proquest.com/medline
  sourceTypes: Aggregation Database
DeliveryMethod no_fulltext_linktorsrc
Discipline Medicine
EISSN 1535-7228
ExternalDocumentID 22952074
Genre Validation Study
Journal Article
Research Support, N.I.H., Extramural
GrantInformation_xml – fundername: NHLBI NIH HHS
  grantid: N01-HC-85086
– fundername: NHLBI NIH HHS
  grantid: N01 HC055222
– fundername: NHLBI NIH HHS
  grantid: U01 HL080295
– fundername: NIA NIH HHS
  grantid: AG20098
– fundername: NHLBI NIH HHS
  grantid: N01 HC075150
– fundername: NIA NIH HHS
  grantid: AG15928
– fundername: NHLBI NIH HHS
  grantid: HL087251
– fundername: NHLBI NIH HHS
  grantid: N01-HC-85081
– fundername: NHLBI NIH HHS
  grantid: N01 HC085079
– fundername: NHLBI NIH HHS
  grantid: N01 HC015103
GroupedDBID ---
--Z
-DZ
-~X
.55
.GJ
08P
0WA
1CY
1HT
1KJ
1QT
23M
2QL
2WC
354
3O-
4.4
41~
53G
5GY
5RE
6J9
6TJ
7K8
85S
8F7
8R4
8R5
AAAHA
AAFWJ
AAIKC
AAJMC
AAKAS
AAMNW
AAQQT
AAWTL
AAWTO
AAYJJ
ABDPE
ABIVO
ABPPZ
ABUFD
ABZEH
ACBMB
ACGFO
ACGOD
ACHQT
ACNCT
ADBBV
ADCOW
ADMHG
ADXHL
ADZCM
AENEX
AERZD
AETEA
AFAZI
AFFNX
AGHSJ
AGNAY
AHJKT
AHMBA
AI.
ALMA_UNASSIGNED_HOLDINGS
ASUFR
BAJDF
BAWUL
BCR
BKOMP
BLC
CGR
CS3
CUY
CVF
DIK
E3Z
EBS
ECM
EIF
EJD
EX3
F5P
F8P
FA8
FJW
G0H
GOZPB
GRPMH
H13
HF~
HZ~
J5H
L7B
LPU
LXL
LXN
MVM
N4W
N9A
NEJ
NHB
NPM
OHT
OK1
OVD
P-O
P2P
PEA
PQQKQ
Q.-
Q2X
RWL
RXW
RYA
S10
SJN
SKT
TAE
TEORI
TR2
TWZ
UBC
UHB
UKR
ULE
UPT
UQL
VH1
VVN
WH7
WHG
WOQ
WOW
X4V
X6Y
X7M
XOL
XSW
XZL
YFH
YOC
YQI
YQJ
YRY
YSK
YWH
YXB
YYQ
YZZ
ZCA
ZGI
ZHY
ZKB
ZRR
ZXP
ZY1
~A~
~X8
7X8
XJT
ID FETCH-LOGICAL-a479t-ac07d7f5305c3e8ae12a8f10de206f4b32a2c0b4373c62bee2bbb5ef80fd389f2
IEDL.DBID 7X8
ISICitedReferencesCount 57
ISICitedReferencesURI http://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestLinkType=CitingArticles&DestApp=WOS_CPL&KeyUT=000308278100012&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D
ISSN 1535-7228
IngestDate Thu Oct 02 09:58:45 EDT 2025
Mon Nov 17 00:32:21 EST 2025
IsPeerReviewed true
IsScholarly true
Issue 9
Language English
LinkModel DirectLink
MergedId FETCHMERGED-LOGICAL-a479t-ac07d7f5305c3e8ae12a8f10de206f4b32a2c0b4373c62bee2bbb5ef80fd389f2
Notes ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ObjectType-Undefined-3
PMID 22952074
PQID 1038592730
PQPubID 23479
ParticipantIDs proquest_miscellaneous_1038592730
pubmed_primary_22952074
PublicationCentury 2000
PublicationDate 2012-09-01
PublicationDateYYYYMMDD 2012-09-01
PublicationDate_xml – month: 09
  year: 2012
  text: 2012-09-01
  day: 01
PublicationDecade 2010
PublicationPlace United States
PublicationPlace_xml – name: United States
PublicationTitle The American journal of psychiatry
PublicationTitleAlternate Am J Psychiatry
PublicationYear 2012
SSID ssj0000372
Score 2.316008
Snippet The trajectory of cognitive decline in patients with late-onset Alzheimer's disease varies widely. Genetic variations in CLU, PICALM, and CR1 are associated...
SourceID proquest
pubmed
SourceType Aggregation Database
Index Database
StartPage 954
SubjectTerms Age of Onset
Aged
Alleles
Alzheimer Disease - complications
Alzheimer Disease - genetics
Alzheimer Disease - psychology
Apolipoprotein E4 - genetics
Bayes Theorem
Clusterin - genetics
Cohort Studies
Dementia - complications
Dementia - genetics
Dementia - psychology
Disease Progression
Female
Genetic Predisposition to Disease - genetics
Humans
Male
Models, Psychological
Monomeric Clathrin Assembly Proteins - genetics
Polymorphism, Single Nucleotide - genetics
Receptors, Complement 3b - genetics
Risk Factors
Title Effect of Alzheimer's disease risk genes on trajectories of cognitive function in the Cardiovascular Health Study
URI https://www.ncbi.nlm.nih.gov/pubmed/22952074
https://www.proquest.com/docview/1038592730
Volume 169
WOSCitedRecordID wos000308278100012&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D
hasFullText
inHoldings 1
isFullTextHit
isPrint
link http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV1bS8MwFA7qRHzxfpk3Igg-VdP0kvZJxnD4srEHhb2VJE1ch7ZbOwX99ea0mcMHQfAlUGig5Jycc5rz5fsQupLm31_FJHVoTKXju5F0hAeDJkAubhK4imqxCTYYRKNRPLQHbpWFVS5iYh2o00LCGfktEHkHsUm25G46c0A1CrqrVkJjFbU8U8qAV7PRki2ceLV4k9nUINlKI3tD2GUhtIezGz4BxkqXQtyAVBf8XmbW6aa3_d8P3UFbttDEncYzdtGKyvfQRt-20vfRrOEtxoXGnZfPscpeVXldYduwwQA5x88QCHGR43nJJ_XxfgbPGn-DjjDkRbAtzsxbY4W7P_CtuLnlhAGt-HGAnnr3j90Hx-ovONxn8dzhkrCU6cCEBGlMxpVLeaRdkipKQu0Lj3IqiQByJBlSoRQVQgRKR0Snpg7S9BCt5UWujhEmqeaMRzL2uOsHgnHuEhVyX4rAF77kbXS5WMzE-Dc0LXiuircqWS5nGx01FkmmDRFHAlLk1NRAJ3-YfYo2wdQNPOwMtbTZ3eocrcv3eVaVF7XjmHEw7H8BHODPQQ
linkProvider ProQuest
openUrl ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Effect+of+Alzheimer%27s+disease+risk+genes+on+trajectories+of+cognitive+function+in+the+Cardiovascular+Health+Study&rft.jtitle=The+American+journal+of+psychiatry&rft.au=Sweet%2C+Robert+A&rft.au=Seltman%2C+Howard&rft.au=Emanuel%2C+James+E&rft.au=Lopez%2C+Oscar+L&rft.date=2012-09-01&rft.eissn=1535-7228&rft.volume=169&rft.issue=9&rft.spage=954&rft_id=info:doi/10.1176%2Fappi.ajp.2012.11121815&rft_id=info%3Apmid%2F22952074&rft_id=info%3Apmid%2F22952074&rft.externalDocID=22952074
thumbnail_l http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1535-7228&client=summon
thumbnail_m http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1535-7228&client=summon
thumbnail_s http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1535-7228&client=summon