schliessen

Filtern

 

Bibliotheken

The mediational effects of FDG hypometabolism on the association between cerebrospinal fluid biomarkers and neurocognitive function.

Positive cerebrospinal fluid (CSF) biomarkers of tau and amyloid beta42 suggest possible active underlying Alzheimer's disease (AD) including neurometabolic dysfunction and neurodegeneration leading to eventual cognitive decline. But the temporal relationship between CSF, imaging markers of neural f... Full description

Journal Title: NeuroImage January 15, 2015, Vol.105, pp.357-368
Main Author: Dowling, N Maritza
Other Authors: Johnson, Sterling C , Gleason, Carey E , Jagust, William J , Dowling, N Maritza
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 1095-9572 ; DOI: 10.1016/j.neuroimage.2014.10.050
Link: http://search.proquest.com/docview/1635005812/?pq-origsite=primo
Zum Text:
SendSend as email Add to Book BagAdd to Book Bag
Staff View
recordid: proquest1635005812
title: The mediational effects of FDG hypometabolism on the association between cerebrospinal fluid biomarkers and neurocognitive function.
format: Article
creator:
  • Dowling, N Maritza
  • Johnson, Sterling C
  • Gleason, Carey E
  • Jagust, William J
  • Dowling, N Maritza
subjects:
  • Aged–Cerebrospinal Fluid
  • Aged, 80 and Over–Metabolism
  • Alzheimer Disease–Physiopathology
  • Biomarkers–Metabolism
  • Brain–Metabolism
  • Cognitive Dysfunction–Physiopathology
  • Fluorodeoxyglucose F18–Cerebrospinal Fluid
  • Humans–Metabolism
  • Male–Physiopathology
  • Middle Aged–Metabolism
  • Positron-Emission Tomography–Methods
  • Radiopharmaceuticals–Metabolism
  • Biomarkers
  • Radiopharmaceuticals
  • Fluorodeoxyglucose F18
  • Alzheimer'S Disease
  • Beta Amyloid
  • Csf Biomarkers
  • Fdg-Pet
ispartof: NeuroImage, January 15, 2015, Vol.105, pp.357-368
description: Positive cerebrospinal fluid (CSF) biomarkers of tau and amyloid beta42 suggest possible active underlying Alzheimer's disease (AD) including neurometabolic dysfunction and neurodegeneration leading to eventual cognitive decline. But the temporal relationship between CSF, imaging markers of neural function, and cognition has not been described. Using a statistical mediation model, we examined relationships between cerebrospinal fluid (CSF) analytes (hyperphosphorylated tau (p-Tau181p), β-amyloid peptides 1–42 (Aβ1–42), total tau (t-Tau), and their ratios); change in cognitive function; and change in [18F]fluorodeoxyglucose (FDG) uptake using positron emission tomography (PET). We hypothesized that a) abnormal CSF protein values at baseline, result in cognitive declines by decreasing neuronal glucose metabolism across time, and b) the role of altered glucose metabolism in the assumed causal chain varies by brain region and the nature of CSF protein alteration.Data from 412 individuals participating in Alzheimer's Disease Neuroimaging (ADNI) cohort studies were included in analyses. At baseline, individuals were cognitively normal (N=82), or impaired: 241 with mild cognitive impairment, and 89 with Alzheimer's disease. A parallel-process latent growth curve model was used to test mediational effects of changes in regional FDG-PET uptake over time in relation to baseline CSF biomarkers and changes in cognition, measured with the 13-item Alzheimer Disease's Assessment Scale–cognitive subscale (ADAS–Cog).Findings suggested a causal sequence of events; specifically, FDG hypometabolism acted as a mediator between antecedent CSF biomarker alterations and subsequent cognitive impairment. Higher baseline concentrations of t-Tau, and p-Tau181p were more predictive of decline in cerebral glucose metabolism than lower baseline concentrations of Aβ1–42. FDG-PET changes appeared to mediate t-Tau or t-Tau/Aβ1–42-associated cognitive change across all brain regions examined. Significant direct effects of alterations in Aβ1–42 levels on hypometabolism were observed in a single brain region: middle/inferior temporal gyrus.Results support a temporal framework model in which reduced CSF amyloid-related biomarkers occur earlier in the pathogenic pathway, ultimately leading to detrimental cognitive effects. Also consistent with this temporal framework model, baseline markers of neurofibrillary degeneration predicted changes in brain glucose metabolism in turn causing longitudina
language: eng
source:
identifier: E-ISSN: 1095-9572 ; DOI: 10.1016/j.neuroimage.2014.10.050
fulltext: fulltext
issn:
  • 10959572
  • 1095-9572
url: Link


@attributes
ID818609929
RANK0.07
NO1
SEARCH_ENGINEprimo_central_multiple_fe
SEARCH_ENGINE_TYPEPrimo Central Search Engine
LOCALfalse
PrimoNMBib
record
control
sourcerecordid1635005812
sourceidproquest
recordidTN_proquest1635005812
sourcesystemPC
pqid1635005812
display
typearticle
titleThe mediational effects of FDG hypometabolism on the association between cerebrospinal fluid biomarkers and neurocognitive function.
creatorDowling, N Maritza ; Johnson, Sterling C ; Gleason, Carey E ; Jagust, William J ; Dowling, N Maritza
contributorWeiner, Michael W (correspondence author) ; Aisen, Paul (record owner) ; Weiner, Michael ; Aisen, Paul ; Petersen, Ronald ; Jack, Clifford R ; Jagust, William ; Trojanowki, John Q ; Toga, Arthur W ; Beckett, Laurel ; Green, Robert C ; Saykin, Andrew J ; Morris, John ; Shaw, Leslie M ; Khachaturian, Zaven ; Sorensen, Greg ; Carrillo, Maria ; Kuller, Lew ; Raichle, Marc ; Paul
ispartofNeuroImage, January 15, 2015, Vol.105, pp.357-368
identifierE-ISSN: 1095-9572 ; DOI: 10.1016/j.neuroimage.2014.10.050
subjectAged–Cerebrospinal Fluid ; Aged, 80 and Over–Metabolism ; Alzheimer Disease–Physiopathology ; Biomarkers–Metabolism ; Brain–Metabolism ; Cognitive Dysfunction–Physiopathology ; Fluorodeoxyglucose F18–Cerebrospinal Fluid ; Humans–Metabolism ; Male–Physiopathology ; Middle Aged–Metabolism ; Positron-Emission Tomography–Methods ; Radiopharmaceuticals–Metabolism ; Biomarkers ; Radiopharmaceuticals ; Fluorodeoxyglucose F18 ; Alzheimer'S Disease ; Beta Amyloid ; Csf Biomarkers ; Fdg-Pet
languageeng
source
descriptionPositive cerebrospinal fluid (CSF) biomarkers of tau and amyloid beta42 suggest possible active underlying Alzheimer's disease (AD) including neurometabolic dysfunction and neurodegeneration leading to eventual cognitive decline. But the temporal relationship between CSF, imaging markers of neural function, and cognition has not been described. Using a statistical mediation model, we examined relationships between cerebrospinal fluid (CSF) analytes (hyperphosphorylated tau (p-Tau181p), β-amyloid peptides 1–42 (Aβ1–42), total tau (t-Tau), and their ratios); change in cognitive function; and change in [18F]fluorodeoxyglucose (FDG) uptake using positron emission tomography (PET). We hypothesized that a) abnormal CSF protein values at baseline, result in cognitive declines by decreasing neuronal glucose metabolism across time, and b) the role of altered glucose metabolism in the assumed causal chain varies by brain region and the nature of CSF protein alteration.Data from 412 individuals participating in Alzheimer's Disease Neuroimaging (ADNI) cohort studies were included in analyses. At baseline, individuals were cognitively normal (N=82), or impaired: 241 with mild cognitive impairment, and 89 with Alzheimer's disease. A parallel-process latent growth curve model was used to test mediational effects of changes in regional FDG-PET uptake over time in relation to baseline CSF biomarkers and changes in cognition, measured with the 13-item Alzheimer Disease's Assessment Scale–cognitive subscale (ADAS–Cog).Findings suggested a causal sequence of events; specifically, FDG hypometabolism acted as a mediator between antecedent CSF biomarker alterations and subsequent cognitive impairment. Higher baseline concentrations of t-Tau, and p-Tau181p were more predictive of decline in cerebral glucose metabolism than lower baseline concentrations of Aβ1–42. FDG-PET changes appeared to mediate t-Tau or t-Tau/Aβ1–42-associated cognitive change across all brain regions examined. Significant direct effects of alterations in Aβ1–42 levels on hypometabolism were observed in a single brain region: middle/inferior temporal gyrus.Results support a temporal framework model in which reduced CSF amyloid-related biomarkers occur earlier in the pathogenic pathway, ultimately leading to detrimental cognitive effects. Also consistent with this temporal framework model, baseline markers of neurofibrillary degeneration predicted changes in brain glucose metabolism in turn causing longitudinal cognitive changes, suggesting that tau-related burden precedes neurometabolic dysfunction. While intriguing, the hypothesized mediational relationships require further validation. •A statistical mediation analysis is used to assess potential causal mechanisms.•The assumed causal chain is tested in selected disease-vulnerable brain regions.•Hypometabolism was a mediator of antecedent biomarkers and later cognitive decline.•Tau-related pathology had stronger associations with cognition than amyloid burden.•Glucose uptake changes mediated tau-related cognitive changes in all brain regions.
version6
lds50peer_reviewed
links
openurl$$Topenurl_article
openurlfulltext$$Topenurlfull_article
backlink$$Uhttp://search.proquest.com/docview/1635005812/?pq-origsite=primo$$EView_record_in_ProQuest_(subscribers_only)
search
creatorcontrib
0Dowling, N Maritza
1Johnson, Sterling C
2Gleason, Carey E
3Jagust, William J
titleThe mediational effects of FDG hypometabolism on the association between cerebrospinal fluid biomarkers and neurocognitive function.
subject
0Aged–Cerebrospinal Fluid
1Aged, 80 and Over–Metabolism
2Alzheimer Disease–Physiopathology
3Biomarkers–Metabolism
4Brain–Metabolism
5Cognitive Dysfunction–Physiopathology
6Fluorodeoxyglucose F18–Cerebrospinal Fluid
7Humans–Metabolism
8Male–Physiopathology
9Middle Aged–Metabolism
10Positron-Emission...
11Alzheimer's disease
12Beta amyloid
13CSF biomarkers
14FDG-PET
15Longitudinal mediation
16Parallel process latent growth
17Structural equation modeling
18Tau
general
0English
110.1016/j.neuroimage.2014.10.050
2MEDLINE (ProQuest)
3ProQuest Biological Science Collection
4ProQuest Natural Science Collection
5ProQuest SciTech Collection
6Biological Science Database
7Natural Science Collection
8SciTech Premium Collection
9Health Research Premium Collection
10Health Research Premium Collection (Alumni edition)
11Biological Science Index (ProQuest)
sourceidproquest
recordidproquest1635005812
issn
010959572
11095-9572
rsrctypearticle
creationdate2015
addtitleNeuroImage
searchscope
01007527
11007944
21009130
310000004
410000038
510000050
610000120
710000159
810000238
910000253
1010000260
1110000270
1210000271
1310000302
1410000350
15proquest
scope
01007527
11007944
21009130
310000004
410000038
510000050
610000120
710000159
810000238
910000253
1010000260
1110000270
1210000271
1310000302
1410000350
15proquest
lsr43
01007527false
11007944false
21009130false
310000004false
410000038false
510000050false
610000120false
710000159false
810000238false
910000253false
1010000260false
1110000270false
1210000271false
1310000302false
1410000350false
contributor
0Weiner, Michael W
1Aisen, Paul
2Weiner, Michael
3Petersen, Ronald
4Jack, Clifford R
5Jagust, William
6Trojanowki, John Q
7Toga, Arthur W
8Beckett, Laurel
9Green, Robert C
10Saykin, Andrew J
11Morris, John
12Shaw, Leslie M
13Khachaturian, Zaven
14Sorensen, Greg
15Carrillo, Maria
16Kuller, Lew
17Raichle, Marc
18Paul, Steven
19Davies, Peter
20Fillit, Howard
21Hefti, Franz
22Holtzman, Davie
23Mesulam, M Marcel
24Potter, William
25Snyder, Peter
26Schwartz, Adam
27Montine, Tom
28Thomas, Ronald G
29Donohue, Michael
30Walter, Sarah
31Gessert, Devon
32Sather, Tamie
33Jiminez, Gus
34Harvey, Danielle
35Bernstein, Matthew
36Fox, Nick
37Thompson, Paul
38Schuff, Norbert
39Decarli, Charles
40Borowski, Bret
41Gunter, Jeff
42Senjem, Matt
43Vemuri, Prashanthi
44Jones, David
45Kantarci, Kejal
46Ward, Chad
47Koeppe, Robert A
48Foster, Norm
49Reiman, Eric M
50Chen, Kewei
51Mathis, Chet
52Landau, Susan
53Morris, John C
54Cairns, Nigel J
55Householder, Erin
56Taylor-Reinwald, Lisa
57Lee, Virginia
58Korecka, Magdalena
59Figurski, Michal
60Crawford, Karen
61Neu, Scott
62Foroud, Tatiana M
63Potkin, Steven
64Shen, Li
65Faber, Kelley
66Kim, Sungeun
67Nho, Kwangsik
68Thal, Lean
69Thal, Leon
70Buckholtz, Neil
71Snyder, Peter J
72Albert, Marylyn
73Frank, Richard
74Consulting, Richard Frank
75Hsiao, John
76Kaye, Jeffrey
77Quinn, Joseph
78Lind, Betty
79Carter, Raina
80Dolen, Sara
81Schneider, Lon S
82Pawluczyk, Sonia
83Beccera, Mauricio
84Teodoro, Liberty
85Spann, Bryan M
86Brewer, James
87Vanderswag, Helen
88Fleisher, Adam
89Heidebrink, Judith L
90Lord, Joanne L
91Mason, Sara S
92Albers, Colleen S
93Knopman, David
94Johnson, Kris
95Doody, Rachelle S
96Villanueva-Meyer, Javier
97Chowdhury, Munir
98Rountree, Susan
99Dang, Mimi
100...
startdate20150115
enddate20150115
citationpf 357 pt 368 vol 105
lsr30VSR-Enriched:[pqid, issn, description]
sort
titleThe mediational effects of FDG hypometabolism on the association between cerebrospinal fluid biomarkers and neurocognitive function.
authorDowling, N Maritza ; Johnson, Sterling C ; Gleason, Carey E ; Jagust, William J ; Dowling, N Maritza
creationdate20150115
lso0120150115
facets
frbrgroupid2798906267912190881
frbrtype5
newrecords20181218
languageeng
creationdate2015
topic
0Aged–Cerebrospinal Fluid
1Aged, 80 and Over–Metabolism
2Alzheimer Disease–Physiopathology
3Biomarkers–Metabolism
4Brain–Metabolism
5Cognitive Dysfunction–Physiopathology
6Fluorodeoxyglucose F18–Cerebrospinal Fluid
7Humans–Metabolism
8Male–Physiopathology
9Middle Aged–Metabolism
10Positron-Emission...
collection
0MEDLINE (ProQuest)
1ProQuest Biological Science Collection
2ProQuest Natural Science Collection
3ProQuest SciTech Collection
4Biological Science Database
5Natural Science Collection
6SciTech Premium Collection
7Health Research Premium Collection
8Health Research Premium Collection (Alumni edition)
9Biological Science Index (ProQuest)
prefilterarticles
rsrctypearticles
creatorcontrib
0Dowling, N Maritza
1Johnson, Sterling C
2Gleason, Carey E
3Jagust, William J
4Weiner, Michael W
5Aisen, Paul
6Weiner, Michael
7Petersen, Ronald
8Jack, Clifford R
9Jagust, William
10Trojanowki, John Q
11Toga, Arthur W
12Beckett, Laurel
13Green, Robert C
14Saykin, Andrew J
15Morris, John
16Shaw, Leslie M
17Khachaturian, Zaven
18Sorensen, Greg
19Carrillo, Maria
20Kuller, Lew
21Raichle, Marc
22Paul, Steven
23Davies, Peter
24Fillit, Howard
25Hefti, Franz
26Holtzman, Davie
27Mesulam, M Marcel
28Potter, William
29Snyder, Peter
30Schwartz, Adam
31Montine, Tom
32Thomas, Ronald G
33Donohue, Michael
34Walter, Sarah
35Gessert, Devon
36Sather, Tamie
37Jiminez, Gus
38Harvey, Danielle
39Bernstein, Matthew
40Fox, Nick
41Thompson, Paul
42Schuff, Norbert
43Decarli, Charles
44Borowski, Bret
45Gunter, Jeff
46Senjem, Matt
47Vemuri, Prashanthi
48Jones, David
49Kantarci, Kejal
50Ward, Chad
51Koeppe, Robert A
52Foster, Norm
53Reiman, Eric M
54Chen, Kewei
55Mathis, Chet
56Landau, Susan
57Morris, John C
58Cairns, Nigel J
59Householder, Erin
60Taylor-Reinwald, Lisa
61Lee, Virginia
62Korecka, Magdalena
63Figurski, Michal
64Crawford, Karen
65Neu, Scott
66Foroud, Tatiana M
67Potkin, Steven
68Shen, Li
69Faber, Kelley
70Kim, Sungeun
71Nho, Kwangsik
72Thal, Lean
73Thal, Leon
74Buckholtz, Neil
75Snyder, Peter J
76Albert, Marylyn
77Frank, Richard
78Consulting, Richard Frank
79Hsiao, John
80Kaye, Jeffrey
81Quinn, Joseph
82Lind, Betty
83Carter, Raina
84Dolen, Sara
85Schneider, Lon S
86Pawluczyk, Sonia
87Beccera, Mauricio
88Teodoro, Liberty
89Spann, Bryan M
90Brewer, James
91Vanderswag, Helen
92Fleisher, Adam
93Heidebrink, Judith L
94Lord, Joanne L
95Mason, Sara S
96Albers, Colleen S
97Knopman, David
98Johnson, Kris
99Doody, Rachelle S
100...
jtitleNeuroImage
toplevelpeer_reviewed
delivery
delcategoryRemote Search Resource
fulltextfulltext
addata
aulast
0Dowling
1Johnson
2Gleason
3Jagust
aufirst
0N Maritza
1Sterling C
2Carey E
3William J
au
0Dowling, N Maritza
1Johnson, Sterling C
2Gleason, Carey E
3Jagust, William J
addau
0Weiner, Michael W
1Aisen, Paul
2Weiner, Michael
3Petersen, Ronald
4Jack, Clifford R
5Jagust, William
6Trojanowki, John Q
7Toga, Arthur W
8Beckett, Laurel
9Green, Robert C
10Saykin, Andrew J
11Morris, John
12Shaw, Leslie M
13Khachaturian, Zaven
14Sorensen, Greg
15Carrillo, Maria
16Kuller, Lew
17Raichle, Marc
18Paul, Steven
19Davies, Peter
20Fillit, Howard
21Hefti, Franz
22Holtzman, Davie
23Mesulam, M Marcel
24Potter, William
25Snyder, Peter
26Schwartz, Adam
27Montine, Tom
28Thomas, Ronald G
29Donohue, Michael
30Walter, Sarah
31Gessert, Devon
32Sather, Tamie
33Jiminez, Gus
34Harvey, Danielle
35Bernstein, Matthew
36Fox, Nick
37Thompson, Paul
38Schuff, Norbert
39DeCArli, Charles
40Borowski, Bret
41Gunter, Jeff
42Senjem, Matt
43Vemuri, Prashanthi
44Jones, David
45Kantarci, Kejal
46Ward, Chad
47Koeppe, Robert A
48Foster, Norm
49Reiman, Eric M
50Chen, Kewei
51Mathis, Chet
52Landau, Susan
53Morris, John C
54Cairns, Nigel J
55Householder, Erin
56Taylor-Reinwald, Lisa
57Lee, Virginia
58Korecka, Magdalena
59Figurski, Michal
60Crawford, Karen
61Neu, Scott
62Foroud, Tatiana M
63Potkin, Steven
64Shen, Li
65Faber, Kelley
66Kim, Sungeun
67Nho, Kwangsik
68Thal, Lean
69Thal, Leon
70Buckholtz, Neil
71Snyder, Peter J
72Albert, Marylyn
73Frank, Richard
74Consulting, Richard Frank
75Hsiao, John
76Kaye, Jeffrey
77Quinn, Joseph
78Lind, Betty
79Carter, Raina
80Dolen, Sara
81Schneider, Lon S
82Pawluczyk, Sonia
83Beccera, Mauricio
84Teodoro, Liberty
85Spann, Bryan M
86Brewer, James
87Vanderswag, Helen
88Fleisher, Adam
89Heidebrink, Judith L
90Lord, Joanne L
91Mason, Sara S
92Albers, Colleen S
93Knopman, David
94Johnson, Kris
95Doody, Rachelle S
96Villanueva-Meyer, Javier
97Chowdhury, Munir
98Rountree, Susan
99Dang, Mimi
100...
atitleThe mediational effects of FDG hypometabolism on the association between cerebrospinal fluid biomarkers and neurocognitive function.
jtitleNeuroImage
risdate20150115
volume105
spage357
epage368
pages357-368
eissn1095-9572
formatjournal
genrearticle
ristypeJOUR
doi10.1016/j.neuroimage.2014.10.050
urlhttp://search.proquest.com/docview/1635005812/
issn10538119
date2015-01-15