Developmental amnesia and its relationship to degree of hippocampal atrophy

E Isaacs

F Vargha-Khadem

K Watkins

A Lucas

M Mishkin

D Gadian

^{Institute of Child Health, University College London, London WC1N 1EH, United Kingdom;}^{Montreal Neurological Institute, McGill University, Montreal, QC, Canada H3A 1S2; and}^{National Institute of Mental Health, Bethesda, MD 20892}

^{To whom correspondence should be addressed at: Room 1B80, Building 49, 49 Convent Drive, National Institutes of Health, Bethesda, MD 20892. E-mail:}vog.hin.hmin.nl@mm.

Contributed by M. Mishkin, June 19, 2003

Abstract

Two groups of adolescents, one born preterm and one with a diagnosis of developmental amnesia, were compared with age-matched normal controls on measures of hippocampal volume and memory function. Relative to control values, the preterm group values showed a mean bilateral reduction in hippocampal volume of 8–9% (ranging to 23%), whereas the developmental amnesic group values showed a reduction of 40% (ranging from 27% to 56%). Despite equivalent IQ and immediate memory scores in the two study groups, there were marked differences between them on a wide variety of verbal and visual delayed memory tasks. Consistent with their diagnosis, the developmental amnesic group was impaired relative to both other groups on nearly all delayed memory measures. The preterm group, by contrast, was significantly impaired relative to the controls on only a few memory measures, i.e., route following and prospective memory. We suggest that early hippocampal pathology leads to the disabling memory impairments associated with developmental amnesia when the volume of this structure is reduced below normal by ≈20–30% on each side. Whether this is a sufficient condition for the disorder or whether abnormality in other brain regions is also necessary remains to be determined.

Abstract

Developmental amnesia is a selective disorder characterized by marked impairment in episodic memory despite relatively preserved semantic memory (1, 2). The disorder is associated with bilateral medial temporal pathology that seems to be restricted mainly to the hippocampus, with some involvement of the putamen, thalamus, and right retrosplenial cortex demonstrated in voxel-based morphometry studies (2–4). Because of their frequent failure to remember the events of everyday life, children with developmental amnesia are seriously disabled, yet they have managed to acquire literacy skills and factual knowledge in line with a level of intellectual ability that ranges from low to high average. The disorder has been observed in children with pathology incurred at ages extending from birth to puberty (3, 4), with a frequent etiology of one or more hypoxic/ischemic episodes.

An important question raised by these findings concerns what degree of damage gives rise to developmental amnesia. Because medial temporal pathology seems to play a critical role in the disorder, and because the clearest indicator in the cases studied is hippocampal atrophy, the question becomes one of determining how much hippocampal atrophy is necessary for the condition to emerge.

Here we compare a group of children with developmental amnesia (DA group) with another group that has a significant reduction in hippocampal volume and yet does not exhibit the same disabling memory impairments (5). The latter group consisted of children born preterm with very low birth weight (PT group). Direct comparison between the two groups, in terms of both their memory abilities and hippocampal volumes, could help to determine the amount of damage that causes developmental amnesia and, more generally, the mnemonic deficits produced by different degrees of hippocampal atrophy.

Mean left and right volumes (in mm^{) and volumes expressed as a percentage of the C group mean are given. LHCV, left hippocampal volume; RHCV, right hippocampal volume.}

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Acknowledgments

We thank the willing participants and their families. This work was supported by the Medical Research Council, The Wellcome Trust, and National Institute of Mental Health Intramural Research Program/National Institutes of Health/Department of Health and Human Services. Research at the Institute of Child Health and Great Ormond Street Hospital for Children NHS Trust benefits from research and development funding from the National Health Service Executive.

Acknowledgments

Notes

Abbreviations: DA group, developmental amnesia group; PT group, preterm group; C group, control group; yr, year.

Notes

Abbreviations: DA group, developmental amnesia group; PT group, preterm group; C group, control group; yr, year.

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