TY - JOUR
T1 - Fornix integrity and hippocampal volume predict memory decline and progression to Alzheimer's disease
AU - Mielke, Michelle M.
AU - Okonkwo, Ozioma C.
AU - Oishi, Kenichi
AU - Mori, Susumu
AU - Tighe, Sarah
AU - Miller, Michael I.
AU - Ceritoglu, Can
AU - Brown, Timothy
AU - Albert, Marilyn
AU - Lyketsos, Constantine G.
N1 - Funding Information:
Constantine G. Lyketsos received grant support (research or CME) from NIMH, NIA, Associated Jewish Federation of Baltimore, Weinberg Foundation, Forest, GlaxoSmithKline, Eisai, Pfizer, Astra-Zeneca, Lilly, Ortho-McNeil, Bristol-Myers, and Novartis; works as a consultant/advisor to AstraZeneca, GlaxoSmithKline, Eisai, Novartis, Forest, Supernus, Adlyfe, Takeda, Wyeth, Lundbeck, Merz, Lilly, Genentech, and Elan; and has received honorarium or travel support from Pfizer, Forest, GlaxoSmithKline, and Health Monitor. All other authors have no disclosures.
Funding Information:
The authors thank Dr. Gwenn Smith for comments on the manuscript. This research was funded in part by grants from GlaxoSmithKline, the National Institute on Aging ( P50-AG005146 , P50-AG021334 , R21AG033774 , and R21NS060271-01 ), and the National Institute of Research Resources ( NCRR, P41-RR15241 ). NCRR is a component of the National Institutes of Health. The manuscript’s contents are solely the responsibility of the authors and do not necessarily represent the official view of NCRR or the National Institutes of Health.
PY - 2012/3
Y1 - 2012/3
N2 - Background: The fornix is the predominant outflow tract of the hippocampus, a brain region known to be affected early in the course of Alzheimer's disease (AD). The aims of the present study were to: (1) examine the cross-sectional relationship between fornix diffusion tensor imaging (DTI) measurements (fractional anisotropy [FA], mean diffusivity [MD], axial diffusivity, and radial diffusivity), hippocampal volume, and memory performance, and (2) compare fornix DTI measures with hippocampal volumes as predictors of progression and transition from amnestic mild cognitive impairment to AD dementia. Methods: Twenty-three mild cognitive impairment participants for whom hippocampal volumetry and DTI were conducted at baseline received detailed evaluations at baseline; 3, 6, and 12 months; and 2.5 years. Six participants converted to AD over the follow-up period. Fornix and posterior cingulum DTI measurements and hippocampal volumes were ascertained using manual measures. Random effects models assessed each of the neuroimaging measures as predictors of decline on the Mini-Mental State Examination, Clinical Dementia Rating-sum of boxes, and memory z scores; receiver operating characteristic analyses examined the predictive value for conversion to AD. Results: There was a significant correlation between fornix FA and hippocampal volumes. However, only the fornix measurements (FA, MD, radial diffusivity, and axial diffusivity) were cross-sectionally correlated with memory z scores. Both fornix FA and hippocampal volumes were predictive of memory decline. Individually, fornix FA and MD and hippocampal volumes were very good predictors of progression, with likelihood ratios >83, and better than 90% accuracy. Conclusion: Fornix FA both cross-sectionally correlated with and longitudinally predicted memory decline and progression to AD. Manually drawn region of interest within the fornix shows promise comparable with hippocampal volume as a predictive biomarker of progression, and this finding warrants replication in a larger study.
AB - Background: The fornix is the predominant outflow tract of the hippocampus, a brain region known to be affected early in the course of Alzheimer's disease (AD). The aims of the present study were to: (1) examine the cross-sectional relationship between fornix diffusion tensor imaging (DTI) measurements (fractional anisotropy [FA], mean diffusivity [MD], axial diffusivity, and radial diffusivity), hippocampal volume, and memory performance, and (2) compare fornix DTI measures with hippocampal volumes as predictors of progression and transition from amnestic mild cognitive impairment to AD dementia. Methods: Twenty-three mild cognitive impairment participants for whom hippocampal volumetry and DTI were conducted at baseline received detailed evaluations at baseline; 3, 6, and 12 months; and 2.5 years. Six participants converted to AD over the follow-up period. Fornix and posterior cingulum DTI measurements and hippocampal volumes were ascertained using manual measures. Random effects models assessed each of the neuroimaging measures as predictors of decline on the Mini-Mental State Examination, Clinical Dementia Rating-sum of boxes, and memory z scores; receiver operating characteristic analyses examined the predictive value for conversion to AD. Results: There was a significant correlation between fornix FA and hippocampal volumes. However, only the fornix measurements (FA, MD, radial diffusivity, and axial diffusivity) were cross-sectionally correlated with memory z scores. Both fornix FA and hippocampal volumes were predictive of memory decline. Individually, fornix FA and MD and hippocampal volumes were very good predictors of progression, with likelihood ratios >83, and better than 90% accuracy. Conclusion: Fornix FA both cross-sectionally correlated with and longitudinally predicted memory decline and progression to AD. Manually drawn region of interest within the fornix shows promise comparable with hippocampal volume as a predictive biomarker of progression, and this finding warrants replication in a larger study.
KW - Biomarker
KW - Diffusion tensor imaging
KW - Fornix
KW - Hippocampus
KW - Mild cognitive impairment
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U2 - 10.1016/j.jalz.2011.05.2416
DO - 10.1016/j.jalz.2011.05.2416
M3 - Article
C2 - 22404852
AN - SCOPUS:84863408579
SN - 1552-5260
VL - 8
SP - 105
EP - 113
JO - Alzheimer's and Dementia
JF - Alzheimer's and Dementia
IS - 2
ER -