Jenny Harasty

Topography of brain atrophy during normal aging and alzheimer's disease

The present study investigated the effect of age on total and regional brain volumes and compared age-associated changes in 20 healthy controls with those observed in 12 patients with Alzheimers disease (AD). Weights and volumes of the whole brain and cerebrum, as well as the fractional volumes of the frontal, temporal, and parieto-occipital cortices, medial temporal structures, deep brain structures, and white matter were measured. Males had larger and heavier brains than females of comparable age. A small decline in brain volume with age was found (approximately 2 ml per year), but only within the white matter. In comparison, no further loss of white matter occurred in AD; however, the cerebral cortex was significantly reduced in volume, with the greatest loss from the medial temporal structures. This loss was related to disease progression; greater proportional loss was associated with more rapid decline in older patients. This study suggests that significant brain atrophy is not a consequence of advancing age. In addition, it suggests a regional specificity of damage in AD.

Glial fibrillary acidic protein (GFAP) immunohistochemistry in human cortex: a quantitative study using different antisera

Glial fibrillary acidic protein (GFAP) is the principal marker for brain astrocytes. The present study aims to examine the variability in GFAP immunohistochemistry in formalin-fixed human brain. Four commercially-available antisera were tested using standardised protocols in the cerebral cortex of three cases with prominent glial reactions and one control. GFAP immunoreactivity was largely confined to the pial surface and white matter in control cortex, with the number of astrocytic cell bodies and processes as well as intensity of staining markedly increased in damaged cortices. A dramatic difference in the pattern of GFAP staining using different antisera was observed and may account for discrepancies between past studies. This variance has important practical implications for the interpretation of results using GFAP immunohistochemistry in human tissue.

White matter loss in healthy ageing: a postmortem analysis.

Age-related brain changes are widely documented. Because of differences in measurement methods and case selection, the reported effects of age on regional grey and white matter brain volumes, however, are much more pronounced and widespread in neuroimaging than in postmortem studies. Consequently, the magnitude of the effect that is specific to chronological age remains unresolved. We present postmortem volume measurements for 26 cortical, subcortical and white matter regions, in 24 human brains aged 46-92 years, free of neuropathological abnormalities. Significant age-related loss was observed in anterior and posterior white matter but not in total grey matter volumes. Further analyses on five cortical subregions previously reported to exhibit large age-related loss on MRI yielded negative results. These analyses demonstrate smaller changes with age than those reported in imaging studies. Although this discrepancy between postmortem and imaging studies may partly be explained by the increase in noise of the neuroimaging data with age, our results suggest that healthy brain ageing is a process affecting predominantly white matter not grey matter.

Cortical degeneration associated with phonologic and semantic language impairments in AD.

Objective: To compare the pattern of cortical degeneration associated with different language deficits in cases of AD. Methods: Cases for detailed neuropathologic analysis (Patients 1 and 2) were selected because of their detailed clinical and neuropsychological assessments of language dysfunction in AD. Patient 1 had severe phonologic impairment with relatively preserved semantic aspects of language. Patient 2 had severe semantic language impairment with relatively preserved phonologic skills. The tissue volume of cortical regions associated with speech and language function was measured using standardized three-dimensional techniques. Neuronal areal fraction was also measured from histologic tissue samples. The degree of volume atrophy and neuronal loss was calculated in comparison to control measures (n = 10 men and 11 women). Measurements more than 2 SD from controls were considered abnormal. Results: Both AD cases had significant degeneration of the superior temporal gyrus and area 37. Cortical language regions affected only in Patient 1 included the anterior and posterior insula and part of Broca’s area. In contrast, Patient 2 had a greater degree of degeneration in the temporal gyri and their white matter connections with the hippocampal/entorhinal complex. Conclusions: Variable patterns of neurodegeneration underlie the clinical differences observed in patients with AD. Disconnection within the temporal lobe appears associated with semantic language difficulties, whereas disconnection of the anterior and posterior language areas appears associated with phonologic and grammatical impairment.

Reproducible sampling regimen for specific cortical regions: application to speech-associated areas

The variability in the external gyri pattern of human brains has made the identification of specific cortical areas difficult. Studies correlating cortical structure and function have not consistently controlled for this variability. The aim of the present study was to develop a reliable and reproducible regimen for sampling five speech-associated and one non-speech associated cortical region in the human brain. The gyri of interest were labelled using non-aqueous dye prior to coronal slicing of brains at 3 mm intervals. Using the labelled gyri, a set of internal brain landmarks was established to aid in sampling one block of each cortical region of interest. The position of each internal landmark was determined as a percentage of the total brain length and breadth. The variability in the position of each internal landmark was investigated using analysis of variance and found to be consistent in three dimensions in all cases. The correlation of the sampled cortical region to the internal landmark was consistent in different cases with point to point agreement of 100%. This contrasts with the variability between cases in external gyri features. The sampled region was tested to determine cytoarchitectural variability by measuring the depth of each cortical layer. This technique found that the same cytoarchitectural regions were sampled in each case. As expected, these regions were distinguishable by the significant difference in the depth of different cortical layers. Accurate identification of both the external gyri and internal landmarks occurred with interrater point to point agreement of 90-100%.