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Fractional anisotropy of the fornix and hippocampal atrophy in Alzheimer's disease.

Kantarci K - Front Aging Neurosci (2014)

Bottom Line: Fornix also carries the afferent cholinergic and GABAergic projections from the medial septal nuclei and the adjacent diagonal band back to the medial temporal lobe, interconnecting the core limbic structures.Because fornix carries the axons projecting from the hippocampus, integrity of the fornix is in-part linked to the integrity of the hippocampus.In keeping with that, fornix FA is reduced in subjects with hippocampal atrophy, correlating with memory function.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiology, Mayo Clinic , Rochester, MN , USA.

ABSTRACT
Decrease in the directionality of water diffusion measured with fractional anisotropy (FA) on diffusion tensor imaging has been linked to loss of myelin and axons in the white matter. Fornix FA is consistently decreased in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD). Furthermore, decreased fornix FA is one of the earliest MRI abnormalities observed in cognitively normal individuals who are at an increased risk for AD, such as in pre-symptomatic carriers of familial AD mutations and in pre-clinical AD. Reductions of FA at these early stages, which predicted the decline in memory function. Fornix carries the efferent projections from the CA1 and CA3 pyramidal neurons of the hippocampus and subiculum, connecting these structures to the septal nuclei, anterior thalamic nucleus, mammillary bodies, and medial hypothalamus. Fornix also carries the afferent cholinergic and GABAergic projections from the medial septal nuclei and the adjacent diagonal band back to the medial temporal lobe, interconnecting the core limbic structures. Because fornix carries the axons projecting from the hippocampus, integrity of the fornix is in-part linked to the integrity of the hippocampus. In keeping with that, fornix FA is reduced in subjects with hippocampal atrophy, correlating with memory function. The literature on FA reductions in the fornix in the clinical spectrum of AD from pre-symptomatic carriers of familial AD mutations to pre-clinical AD, MCI, and dementia stages is reviewed.

No MeSH data available.


Related in: MedlinePlus

Fractional anisotropy of the fornix in the cognitively normal (CN) and mild cognitive impairment (MCI) biomarker groups. Hippocampal atrophy on MRI and/or hypometabolism in the Alzheimer signature composite on FDG PET was used to classify subjects into the neurodegeneration-positive group, and high amyloid load on PET was used to classify subjects into the amyloid-positive group. Cut-points for amyloid positivity, hippocampal atrophy, and Alzheimer signature hypometabolism were determined from the 10th percentile of the measurement distributions in clinically diagnosed AD patients as previously described (Jack et al., 2012). Fornix FA was lower in the neurodegeneration positive CN and MCI patients compared to the cognitively normal group with normal imaging findings (amyloid and neurodegeneration negative; p < 0.001). A positive amyloid PET scan was not associated with a reduction in fornix FA, in the absence of co-existent neurodegeneration in cognitively normal individuals (p = 0.19) (Kantarci et al., 2014).
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Figure 1: Fractional anisotropy of the fornix in the cognitively normal (CN) and mild cognitive impairment (MCI) biomarker groups. Hippocampal atrophy on MRI and/or hypometabolism in the Alzheimer signature composite on FDG PET was used to classify subjects into the neurodegeneration-positive group, and high amyloid load on PET was used to classify subjects into the amyloid-positive group. Cut-points for amyloid positivity, hippocampal atrophy, and Alzheimer signature hypometabolism were determined from the 10th percentile of the measurement distributions in clinically diagnosed AD patients as previously described (Jack et al., 2012). Fornix FA was lower in the neurodegeneration positive CN and MCI patients compared to the cognitively normal group with normal imaging findings (amyloid and neurodegeneration negative; p < 0.001). A positive amyloid PET scan was not associated with a reduction in fornix FA, in the absence of co-existent neurodegeneration in cognitively normal individuals (p = 0.19) (Kantarci et al., 2014).

Mentions: The relationship between the structural integrity of hippocampus and fornix has been demonstrated in MCI (Mielke et al., 2012; Zhuang et al., 2012). In a cohort of cognitively normal (CN) older adults (n = 570; median age = 78; interquartile range = 74-83) and MCI (n = 131; median age = 80; interquartile range = 77–86) from the community, both CN and MCI patients showed decreased fornix FA if they also had hippocampal atrophy or AD pattern of hypometabolism on 18F Fluorodeoxyglucose (FDG) PET compared to the CN group with normal hippocampal volumes and metabolism on FDG PET. Having only a positive amyloid-β PET scan with Pittsburgh compound-B (PiB) was not responsible for a reduction in fornix FA in CN individuals, demonstrating that high amyloid load does not influence diffusion tensor imaging (DTI)-based measures of white matter integrity in the absence of co-existent gray matter neurodegeneration in non-demented older adults (Figure 1) (Kantarci et al., 2014). Although individuals with MCI and pre-clinical AD have reductions in fornix FA, it should be noted that a reduction in fornix FA by itself would be insufficient in classifying preclinical and prodromal AD. However, fornix FA can be combined with other imaging biomarkers such as hypometabolism on FDG PET, hippocampal atrophy, and amyloid-β PET for a more accurate classification of individuals at risk for AD, and predicting outcomes.


Fractional anisotropy of the fornix and hippocampal atrophy in Alzheimer's disease.

Kantarci K - Front Aging Neurosci (2014)

Fractional anisotropy of the fornix in the cognitively normal (CN) and mild cognitive impairment (MCI) biomarker groups. Hippocampal atrophy on MRI and/or hypometabolism in the Alzheimer signature composite on FDG PET was used to classify subjects into the neurodegeneration-positive group, and high amyloid load on PET was used to classify subjects into the amyloid-positive group. Cut-points for amyloid positivity, hippocampal atrophy, and Alzheimer signature hypometabolism were determined from the 10th percentile of the measurement distributions in clinically diagnosed AD patients as previously described (Jack et al., 2012). Fornix FA was lower in the neurodegeneration positive CN and MCI patients compared to the cognitively normal group with normal imaging findings (amyloid and neurodegeneration negative; p < 0.001). A positive amyloid PET scan was not associated with a reduction in fornix FA, in the absence of co-existent neurodegeneration in cognitively normal individuals (p = 0.19) (Kantarci et al., 2014).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4230048&req=5

Figure 1: Fractional anisotropy of the fornix in the cognitively normal (CN) and mild cognitive impairment (MCI) biomarker groups. Hippocampal atrophy on MRI and/or hypometabolism in the Alzheimer signature composite on FDG PET was used to classify subjects into the neurodegeneration-positive group, and high amyloid load on PET was used to classify subjects into the amyloid-positive group. Cut-points for amyloid positivity, hippocampal atrophy, and Alzheimer signature hypometabolism were determined from the 10th percentile of the measurement distributions in clinically diagnosed AD patients as previously described (Jack et al., 2012). Fornix FA was lower in the neurodegeneration positive CN and MCI patients compared to the cognitively normal group with normal imaging findings (amyloid and neurodegeneration negative; p < 0.001). A positive amyloid PET scan was not associated with a reduction in fornix FA, in the absence of co-existent neurodegeneration in cognitively normal individuals (p = 0.19) (Kantarci et al., 2014).
Mentions: The relationship between the structural integrity of hippocampus and fornix has been demonstrated in MCI (Mielke et al., 2012; Zhuang et al., 2012). In a cohort of cognitively normal (CN) older adults (n = 570; median age = 78; interquartile range = 74-83) and MCI (n = 131; median age = 80; interquartile range = 77–86) from the community, both CN and MCI patients showed decreased fornix FA if they also had hippocampal atrophy or AD pattern of hypometabolism on 18F Fluorodeoxyglucose (FDG) PET compared to the CN group with normal hippocampal volumes and metabolism on FDG PET. Having only a positive amyloid-β PET scan with Pittsburgh compound-B (PiB) was not responsible for a reduction in fornix FA in CN individuals, demonstrating that high amyloid load does not influence diffusion tensor imaging (DTI)-based measures of white matter integrity in the absence of co-existent gray matter neurodegeneration in non-demented older adults (Figure 1) (Kantarci et al., 2014). Although individuals with MCI and pre-clinical AD have reductions in fornix FA, it should be noted that a reduction in fornix FA by itself would be insufficient in classifying preclinical and prodromal AD. However, fornix FA can be combined with other imaging biomarkers such as hypometabolism on FDG PET, hippocampal atrophy, and amyloid-β PET for a more accurate classification of individuals at risk for AD, and predicting outcomes.

Bottom Line: Fornix also carries the afferent cholinergic and GABAergic projections from the medial septal nuclei and the adjacent diagonal band back to the medial temporal lobe, interconnecting the core limbic structures.Because fornix carries the axons projecting from the hippocampus, integrity of the fornix is in-part linked to the integrity of the hippocampus.In keeping with that, fornix FA is reduced in subjects with hippocampal atrophy, correlating with memory function.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiology, Mayo Clinic , Rochester, MN , USA.

ABSTRACT
Decrease in the directionality of water diffusion measured with fractional anisotropy (FA) on diffusion tensor imaging has been linked to loss of myelin and axons in the white matter. Fornix FA is consistently decreased in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD). Furthermore, decreased fornix FA is one of the earliest MRI abnormalities observed in cognitively normal individuals who are at an increased risk for AD, such as in pre-symptomatic carriers of familial AD mutations and in pre-clinical AD. Reductions of FA at these early stages, which predicted the decline in memory function. Fornix carries the efferent projections from the CA1 and CA3 pyramidal neurons of the hippocampus and subiculum, connecting these structures to the septal nuclei, anterior thalamic nucleus, mammillary bodies, and medial hypothalamus. Fornix also carries the afferent cholinergic and GABAergic projections from the medial septal nuclei and the adjacent diagonal band back to the medial temporal lobe, interconnecting the core limbic structures. Because fornix carries the axons projecting from the hippocampus, integrity of the fornix is in-part linked to the integrity of the hippocampus. In keeping with that, fornix FA is reduced in subjects with hippocampal atrophy, correlating with memory function. The literature on FA reductions in the fornix in the clinical spectrum of AD from pre-symptomatic carriers of familial AD mutations to pre-clinical AD, MCI, and dementia stages is reviewed.

No MeSH data available.


Related in: MedlinePlus