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Cortical degeneration associated with phonologic and semantic language impairments in AD

From the Prince of Wales Medical Research Institute (Drs. Harasty and Halliday), Randwick; Faculty of Medicine (Dr. Harasty), University of New South Wales; Centre for Education and Research on Aging (H. Bennett), Concord Hospital, and the School of Communication Sciences and Disorders (Dr. Croot), University of Sydney, Australia; the Cambridge Brain Bank Laboratory (Dr. Xuereb), Department of Pathology, and the MRC Cognition and Brain Sciences Unit (Dr. Hodges), University of Cambridge, England.

Address correspondence and reprint requests to Dr. J. Harasty, Prince of Wales Medical Research Institute, Randwick, Sydney, Australia 2031; e-mail: J.Harasty{at}unsw.edu.au

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.

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