Selective neuroanatornic abnormalities in Down's syndrome and their cognitive correlates

Abstract

We examined the pattern of neuroanatomic abnormalities in adults with Down's syndrome (DS) and the cognitive correlates of these abnormalities. Specifically, we compared this pattern with what would be predicted by the hypotheses attributing DS pathology to either premature aging or Alzheimer's disease. We measured a number of brain regions on MRIs of 25 subjects: 13 persons with the DS phenotype and 12 age- and sex-matched healthy volunteers. Study participants had no history of cardiovascular disease, diabetes, thyroid dysfunction, or seizure disorder. After statistical adjustment for differences in body size, we found that, in comparison with controls, DS subjects had substantially smaller cerebral and cerebellar hemispheres, ventral pons, mammillary bodies, and hippocampal formations. In the cerebellar vermis of DS subjects, we observed smaller lobules VI to VIII without appreciable differences in other regions. In addition, we noted trends for shrinkage of the dorsolateral prefrontal cortex, anterior cingulate gyrus, inferior temporal and parietal cortices, parietal white matter, and pericalcarine cortex in DS subjects compared with normal controls. The parahippocampal gyrus was larger in DS subjects. We found no significant group differences in the volumes of the prefrontal white matter, the orbitofrontal cortex, the pre- and postcentral gyri, or the basal ganglia. We conclude that the pattern of selective cerebral damage in DS does not clearly fit the predictions of the premature aging or Alzheimer's disease hypotheses. To examine the relationship between brain abnormalities and cognitive deficits observed in DS, we correlated the size of brain regions that were significantly reduced in DS with performance on tests of intelligence and language. The correlation analysis suggested age-related decline in the DS subjects in general intelligence and basic linguistic skills. General intelligence and mastery of linguistic concepts correlated negatively with the volume of the parahippocampal gyrus. There was no relationship between total brain size and the cognitive variables.

Increased Dosage of DYRK1A and Brain Volumetric Alterations in a YAC Model of Partial Trisomy 21

“…The brains of DS patients have been reported to be normal at birth, but most postmortem studies on adults have reported low brain weight, a small cerebellum, small frontal and occipital lobes, and a narrow superior temporal gyrus (Becker et al, 1991). Volumetric neuroimaging studies have shown smaller cerebellar, brainstem, and frontal lobes; smaller hippocampus volumes; and enlarged ventricles (Raz et al, 1995), consistent with postmortem studies. Down syndrome is caused by a total or partial triplication of chromosome 21 (Poissonnier et al, 1976).…”

DYRK1A Enhances the Mitogen-activated Protein Kinase Cascade in PC12 Cells by Forming a Complex with Ras, B-Raf, and MEK1

“…The recent observation that the size of dendrites in some brain areas is reduced in DYRK1A haploinsufficient mice indicates that DYRK1A dose reduction could affect the length and the complexity of the dendrites (Fotaki et al, 2002). Moreover, brains of patients with Down syndrome present size reduction, increased astrocyte number, delayed myelination, and several abnormal neuronal differentiation processes (reviewed in Coyle et al, 1986;Becker et al, 1991;Raz et al, 1995). Thus, our finding that overexpression of DYRK1A potentiates the neurite outgrowth of PC12 cells stimulated with NGF supports the fact that DYRK1A may be involved in signaling mechanisms that regulate dendritic differentiation.…”

MR-based in vivo hippocampal volumetrics: 1. Review of methodologies currently employed

“…One of the brain structures which has been a focus of research is the hippocampal formation. Magnetic resonance (MR)-based in vivo measurement of hippocampal volume is an accepted technique, which has been performed in the aged 1 and healthy subjects, 2 and has revealed a number of structural abnormalities in a variety of neurological and psychiatric disorders, such as temporal lobe epilepsy, 3 Huntington's disease, 4 Turner's syndrome, 5 Cushing's disease, 6 Down's syndrome, 7 Alzheimer's disease (AD), 8 mild cognitive impairment, 9 schizophrenia, 10 major depression (MD), 11 bipolar disorder, 12 post-traumatic stress disorder (PTSD), 13 borderline personality disorder, 14 chronic alcoholism, 15 obsessive-compulsive disorder, 16 and panic disorder. 17 The MR-derived hippocampal volumetric technique has demonstrated good validity and reproducibility, [18][19][20] and accuracy of the measurements has been shown by MRI volumetric measurement of phantoms with a known volume.…”