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

Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Alzheimer's & dementia: the journal of the Alzheimer's Association (Impact Factor: 12.41). 03/2012; 8(2):105-13. DOI: 10.1016/j.jalz.2011.05.2416
Source: PubMed


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.

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Available from: Constantine G Lyketsos
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    • "Fornix lesions produce severe memory impairments (Browning et al. 2010; Wilson et al. 2008). Notably, the progression to AD has been tightly associated with axonal degeneration and dysfunction in the fornix (Mielke et al. 2012). Based on these observations, a hypothesis was put forth: fornix DBS could be applied in patients with dementia in order to augment activity within the circuit of Papez and restore memory and cognitive function. "
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    • "Patients with mild cognitive impairment (MCI) have an increased risk of converting to AD dementia [1] [2]. To date, the best established structural imaging biomarker to predict conversion is magnetic resonance imaging (MRI) of hippocampal grey matter (GM) atrophy [3] [4] [5] [6] [7] [8] [9] [10]. Apart from that, we have shown early atrophy of the cholinergic basal forebrain in AD and MCI in earlier studies [11] [12] [13] [14] [15]. "
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    ABSTRACT: Background: Hippocampal grey matter (GM) atrophy predicts conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD). Pilot data suggests that mean diffusivity (MD) in the hippocampus, as measured with diffusion tensor imaging (DTI), may be a more accurate predictor of conversion than hippocampus volume. In addition, previous studies suggest that volume of the cholinergic basal forebrain may reach a diagnostic accuracy superior to hippocampal volume in MCI. Objective: The present study investigated whether increased MD and decreased volume of the hippocampus, the basal forebrain and other AD-typical regions predicted time to conversion from MCI to AD dementia. Methods: 79 MCI patients with DTI and T1-weighted magnetic resonance imaging (MRI) were retrospectively included from the European DTI Study in Dementia (EDSD) dataset. Of these participants, 35 converted to AD dementia after 6-46 months (mean: 21 months). We used Cox regression to estimate the relative conversion risk predicted by MD values and GM volumes, controlling for age, gender, education and center. Results: Decreased GM volume in all investigated regions predicted an increased risk for conversion. Additionally, increased MD in the right basal forebrain predicted increased conversion risk. Reduced volume of the right hippocampus was the only significant predictor in a stepwise model combining all predictor variables. Conclusion: Volume reduction of the hippocampus, the basal forebrain and other AD-related regions was predictive of increased risk for conversion from MCI to AD. In this study, volume was superior to MD in predicting conversion.
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    • "No correlation between FA and episodic memory; ↓FA with age Mielke et al., 2012 23 aMCI [75. "
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    ABSTRACT: The fornix is a part of the limbic system and constitutes the major efferent and afferent white matter tracts from the hippocampi. The underdevelopment of or injuries to the fornix are strongly associated with memory deficits. Its role in memory impairments was suggested long ago with cases of surgical forniceal transections. However, recent advances in brain imaging techniques, such as diffusion tensor imaging have revealed that macrostructural and microstructural abnormalities of the fornix correlated highly with declarative and episodic memory performance. This structure appears to provide a robust and early imaging predictor for memory deficits not only in neurodegenerative and neuroinflammatory diseases, such as Alzheimer’s disease and multiple sclerosis, but also in schizophrenia and psychiatric disorders, and during neurodevelopment and “typical” aging. The objective of the manuscript is to present a systematic review regarding published brain imaging research on the fornix, including the development of its tracts, its role in various neurological diseases, and its relationship to neurocognitive performance in human studies.
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