Fornix integrity and hippocampal volume predict memory decline and progression to Alzheimer's disease

Michelle M Mielke, Ozioma C. Okonkwo, Kenichi Oishi, Susumu Mori, Sarah Tighe, Michael I. Miller, Can Ceritoglu, Timothy Brown, Marilyn Albert, Constantine G. Lyketsos

Research output: Contribution to journalArticle

95 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)105-113
Number of pages9
JournalAlzheimer's and Dementia
Volume8
Issue number2
DOIs
StatePublished - Mar 2012
Externally publishedYes

Fingerprint

Anisotropy
Alzheimer Disease
Diffusion Tensor Imaging
Neuroimaging
ROC Curve
Dementia
Hippocampus
Biomarkers
Brain

Keywords

  • Biomarker
  • Diffusion tensor imaging
  • Fornix
  • Hippocampus
  • Mild cognitive impairment

ASJC Scopus subject areas

  • Health Policy
  • Epidemiology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Developmental Neuroscience
  • Clinical Neurology

Cite this

Fornix integrity and hippocampal volume predict memory decline and progression to Alzheimer's disease. / Mielke, Michelle M; Okonkwo, Ozioma C.; Oishi, Kenichi; Mori, Susumu; Tighe, Sarah; Miller, Michael I.; Ceritoglu, Can; Brown, Timothy; Albert, Marilyn; Lyketsos, Constantine G.

In: Alzheimer's and Dementia, Vol. 8, No. 2, 03.2012, p. 105-113.

Research output: Contribution to journalArticle

Mielke, MM, Okonkwo, OC, Oishi, K, Mori, S, Tighe, S, Miller, MI, Ceritoglu, C, Brown, T, Albert, M & Lyketsos, CG 2012, 'Fornix integrity and hippocampal volume predict memory decline and progression to Alzheimer's disease', Alzheimer's and Dementia, vol. 8, no. 2, pp. 105-113. https://doi.org/10.1016/j.jalz.2011.05.2416
Mielke, Michelle M ; Okonkwo, Ozioma C. ; Oishi, Kenichi ; Mori, Susumu ; Tighe, Sarah ; Miller, Michael I. ; Ceritoglu, Can ; Brown, Timothy ; Albert, Marilyn ; Lyketsos, Constantine G. / Fornix integrity and hippocampal volume predict memory decline and progression to Alzheimer's disease. In: Alzheimer's and Dementia. 2012 ; Vol. 8, No. 2. pp. 105-113.
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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.

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