Early DAT is distinguished from aging by high-dimensional mapping of the hippocampus

Csernansky, John G.; Wang, L.; Joshi, Sarang; Miller, J. Philip; Gado, Mokhtar H.; Kido, Daniel K.; McKeel, Daniel W.; Morris, John C.; Miller, Michael I.

doi:10.1212/wnl.55.11.1636

Cited by 232 publications

(197 citation statements)

References 35 publications

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“…This result represents a replication of our previous findings 2 (Csernansky et al, 2000). However, in our previous study, we used exploratory statistical methods to identify the pattern of hippocampal surface deformation that was associated with early DAT (Csernansky et al, 2000). The observation of such patterns formed the hypothesis that was tested in the present study: we predefined zones on the surface of the hippocampus that were proximal to the underlying subfields, and then tested the specific hypothesis that inward variation of the hippocampal surface in proximity to the CA1 subfield (i.e., LZ) and subiculum (IMZ), but not the remaining subfields (SZ), could be used to characterize subjects with very mild DAT.…”

Section: Discussionsupporting

confidence: 92%

“…The results suggest that irregularities of the hippocampal surface can be used to distinguish subjects with an early form of DAT from nondemented subjects. This result represents a replication of our previous findings 2 (Csernansky et al, 2000). However, in our previous study, we used exploratory statistical methods to identify the pattern of hippocampal surface deformation that was associated with early DAT (Csernansky et al, 2000).…”

Section: Discussionsupporting

confidence: 85%

“…However, in those studies, we did not specifically hypothesize the relationship between DAT and specific hippocampal subfields, even though inward variation of the head and lateral surface of the body of the hippocampus, a pattern that is consistent with degeneration of the CA1 subfield and subiculum, was observed in the subjects with very mild DAT (Csernansky et al, 2000;Wang et al, 2003). Also, in a study of elderly nondemented subjects who later progressed to having very mild DAT, we predefined surface zones approximating the subfields of the hippocampus on a neuroanatomical template and found that time-toconversion was predicted by an inward variation of the zone approximating the CA1 subfield of the left hippocampus (Csernansky et al, 2005).…”

Section: Introductionmentioning

confidence: 78%

“…Left and right hippocampal volumes in each subject were then calculated as the volumes enclosed by the transformed hippocampal surfaces. The reliability and validity of hippocampal volume measurements derived from these transformations have been demonstrated with respect to expert manual outlining of the hippocampus in younger subjects (Haller et al, 1997) and older subjects with and without dementia (Csernansky et al, 2000;Hsu et al, 2002). Values estimating the overlap of hippocampal surface contours produced by these transformations versus manual outlining exceed 80% in such subjects, which is comparable to the accuracy of repeated attempts at manual outlining of the hippocampal surface by the same expert (Haller et al, 1997).…”

Section: Measurement Of Hippocampal Volume and Surface Variationmentioning

confidence: 85%

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Abnormalities of hippocampal surface structure in very mild dementia of the Alzheimer type

et al. 2006

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To better define the pattern of hippocampal deformity early in the course of Alzheimer's disease, we compared the pattern of hippocampal surface variation in subjects with very mild dementia of the Alzheimer type (DAT) and nondemented subjects. The surface of the hippocampus was divided a priori on a neuroanatomical template into three zones approximating the locations of underlying subfields [Csernansky, J.G., Wang, L., Swank, J., Miller, J.P., Gado, M., McKeel, D., Miller, M.I., Morris, J.C., 2005. Preclinical detection of Alzheimer's disease: hippocampal shape and volume predict dementia onset in the elderly. NeuroImage 25, 783-792]; i.e., a lateral zone (LZ) approximating the CA1 subfield, a superior zone (SZ) approximating the combined CA2, CA3, CA4 subfields and the gyrus dentatus (GD), and an inferior-medial zone (IMZ) approximating the subiculum. Large-deformation high-dimensional brain mapping (HDBM-LD) was used to generate the hippocampal surfaces of all subjects and to register the surface zones across subjects. Average variations within each zone were calculated for the subjects with very mild DAT as compared to the average of the nondemented subjects. After correcting for multiple comparisons, the very mild DAT subjects showed significant inward variation in the left and right LZ, the left and right IMZ, but not in the left and right SZ as compared to nondemented subjects. In logistic regression analyses, inward variation of the left and right LZ or IMZ by 0.1 mm relative to the average of the nondemented subjects increased the odds of the subject being a very mild DAT subject (range-1.18 to 1.57) rather than being a nondemented subject. The odds ratios for the left and right SZ were not significant. These results represent a replication of our previous findings [Csernansky, J.G., Wang, L., Joshi, S., Miller, J.P., Gado, M., Kido, D., McKeel, D., Morris, J.C., Miller, M.I., 2000. Early DAT is distinguished from aging by high-dimensional mapping of the hippocampus. Neurology 55, 1636-1643.] and suggest that inward deformities of the hippocampal surface in proximity to the CA1

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 85%

Section: Introductionmentioning

confidence: 78%

Section: Measurement Of Hippocampal Volume and Surface Variationmentioning

confidence: 85%

See 2 more Smart Citations

Abnormalities of hippocampal surface structure in very mild dementia of the Alzheimer type

et al. 2006

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“…One of the most consistently localized neuroanatomical changes found in neuropsychiatric disorders is reduced hippocampal volume, although it should be emphasized that structural decrements have been observed in other brain regions, including the prefrontal cortex and other areas of the temporal lobe (McCarley et al, 1999). Studies of people with schizophrenia, Alzheimer's disease, and depression have shown that the size of the hippocampus is reduced in comparison to individuals without these disorders (Csernansky et al, 2000;McCarley et al, 1999;Sheline et al, 1996). Moreover, correlative neuroimaging studies have revealed associations between reduced hippocampal volume and poorer cognitive performance in schizophrenia (Gur et al, 2000;Heckers, 2001) and Alzheimer's disease (Grundman et al, 2002;Kohler et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

The Effects of Clonidine on Discrete-Trial Delayed Spatial Alternation in Two Rat Models of Memory Loss

Bardgett

Points

Ramsey-Faulkner

et al. 2007

Neuropsychopharmacol

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Spatial memory impairments observed in Alzheimer's disease and schizophrenia have been attributed to many factors, including glutamate hypofunction and reduced hippocampal volume. Clonidine, a non-specific a 2 adrenergic receptor agonist, improves spatial memory in animals treated with the N-methyl-D-aspartate (NMDA) receptor antagonist, phencyclidine; however, its effects on memory deficits produced by other NMDA antagonists or hippocampal damage have not been fully characterized. The purpose of this study was to determine if clonidine could alleviate memory deficits produced by the NMDA antagonist, MK-801, or by excitotoxic hippocampal damage. In the first phase of the study, male rats were pretreated with clonidine (0.01 or 0.05 mg/kg) or saline, and treated with MK-801 (0.1 mg/kg) or saline prior to discrete-trial delayed alternation or radial-arm maze testing. MK-801 impaired delayed alternation performance and increased the number of arm revisits in the radial-arm maze. Clonidine pretreatment significantly alleviated these druginduced deficits. In the second phase of the study, excitotoxic damage was produced in the dorsal hippocampus with NMDA. Hippocampal damage produced a significant impairment in the delayed alternation task, yet pretreatment with clonidine did not alleviate this damage-induced deficit. Taken together, the data indicate that clonidine alleviates memory impairments produced by glutamate hypofunction, but not by hippocampal damage. This caveat may be important in designing treatments for memory disorders not linked to a single pathophysiological mechanism.

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Conversion of Mild Cognitive Impairment to Alzheimer Disease Predicted by Hippocampal Atrophy Maps

Apostolova¹,

Dutton²,

Dinov³

et al. 2006

Arch Neurol

488

351

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Background: While most patients with mild cognitive impairment (MCI) transition to Alzheimer disease (AD), others develop non-AD dementia, remain in the MCI state, or improve. Objective: To test the following hypotheses: smaller hippocampal volumes predict conversion of MCI to AD, whereas larger hippocampal volumes predict cognitive stability and/or improvement; and patients with MCI who convert to AD have greater atrophy in the CA1 hippocampal subfield and subiculum.

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Early DAT is distinguished from aging by high-dimensional mapping of the hippocampus

Abstract: Assessments of hippocampal volume and shape derived from HDBM may be useful in distinguishing early DAT from healthy aging.

Cited by 232 publications

References 35 publications

Abnormalities of hippocampal surface structure in very mild dementia of the Alzheimer type

Abnormalities of hippocampal surface structure in very mild dementia of the Alzheimer type

The Effects of Clonidine on Discrete-Trial Delayed Spatial Alternation in Two Rat Models of Memory Loss

Conversion of Mild Cognitive Impairment to Alzheimer Disease Predicted by Hippocampal Atrophy Maps

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