There has been increasing awareness that some slowly progressive focal cortical syndromes can be the presenting features of Alzheimer's disease, but pathological evidence has been sparse. This clinico-pathological series presents our experience with pathologically proven atypical as well as typical Alzheimer's disease presentations. We report and compare four patterns of presentation: a typical pattern with initial amnesic syndrome (n = 4 cases), progressive visual dysfunction (n = 1), progressive biparietal syndrome (n = 2) and progressive aphasia (n = 6). The aphasic presentations include both fluent and non-fluent aphasic syndromes. The neuropsychological profiles and neuroimaging clearly reflect the presenting clinical features, and show a close relationship to the distribution of pathology in these cases. Of note was the sparing of medial temporal structures (hippocampus and/or entorhinal cortex) in several aphasic cases and the severe occipito-parietal involvement in those with prominent visuospatial disorders at presentation. Our data demonstrate the wide spectrum of Alzheimer's disease presentations. The recognition of atypical presentations of Alzheimer's disease is important when attempting to make an early accurate pre-morbid diagnosis of neurodegenerative disease.

Hippocampal atrophy is not specific for AD but is also seen in semantic dementia. Distinguishing the patients with semantic dementia was the severe global but asymmetric (left > right) atrophy of the amygdala, temporal pole, and fusiform and inferolateral temporal gyri. These findings have implications for diagnosis and understanding of the cognitive deficits in AD and semantic dementia.

The processes required for object naming were addressed in a study of patients with semantic dementia (a selective decline of semantic memory resulting from progressive temporal lobe atrophy) and in a computational model of single-word production. Although all patients with semantic dementia are impaired in both single-word production and comprehension, previous reports had indicated two different patterns: (a) a parallel decline in accuracy of naming and comprehension, with frequent semantic naming errors, suggesting a purely semantic basis for the anomia and (b) a dramatic progressive anomia without commensurate decline in comprehension, which might suggest a mainly postsemantic source of the anomia. Longitudinal data for 16 patients with semantic dementia reflected these two profiles, but with the following additional important specifications: (1) despite a few relatively extreme versions of one or other profile, the full set of cases formed a continuum in the extent of anomia for a given degree of degraded comprehension; (2) the degree of disparity between these two abilities was associated with relative asymmetry in laterality of atrophy: a parallel decline in the two measures characterized patients with greater right- than left-temporal atrophy, while disproportionate anomia occurred with a predominance of atrophy in the left-temporal lobe. In an implemented computational model of naming, semantic representations were distributed across simulated left- and right-temporal regions, but the semantic units on the left were more strongly connected to left-lateralized phonological representations. Asymmetric damage to semantic units reproduced the longitudinal patient profiles of naming relative to comprehension, plus additional characteristics of the patients' naming performance. On the basis of both the neuropsychological and computational evidence, we propose that semantic impairment alone can account for the full range of word production deficits described here.

The development of novel treatments for Alzheimer’s disease (AD), aimed at ameliorating symptoms and modifying disease processes, increases the need for early diagnosis. Neuropsychological deficits such as poor episodic memory are a consistent feature of early-in-the-course AD, but they overlap with the cognitive impairments in other disorders such as depression, making differential diagnosis difficult. Computerised and traditional tests of memory, attention and executive function were given to four subject groups: mild AD (n = 26); questionable dementia (QD; n = 43); major depression (n = 37) and healthy controls (n = 39). A visuo-spatial associative learning test accurately distinguished AD from depressed/control subjects and revealed an apparent sub-group of QD patients who performed like AD patients. QD patients’ performance correlated with the degree of subsequent global cognitive decline. Elements of contextual and cued recall may account for the task’s sensitivity and specificity for AD.

Objectives-Temporal lobe atrophy as assessed by MRI can be measured in several ways. Volumetric measurements are quantitative but very time consuming and require extensive training to perform, so are not easily transferable to clinical practice. Visual rating scales, by contrast, are quick and widely applicable. Although medial temporal lobe atrophy is well described in Alzheimer's disease (AD), it is uncertain how early these changes can be detected and whether they discriminate AD from other neurodegenerative diseases, most notably frontotemporal dementia (FTD). The objectives were (1) to develop a widely applicable temporal lobe rating scale, and (2) to characterise and quantify the patterns of temporal lobe atrophy in AD versus temporal and frontal variants of FTD. Methods-The temporal lobe assessments were made using an established hippocampal rating scale extended to incorporate additional temporal regions. This was firstly validated with volumetric analysis and then applied to 30 probable AD, 30 FTD (consisting of 17 temporal variant (semantic dementia) and 13 frontal variant) and 18 control coronal MRI images. Results-Bilateral hippocampal atrophy was found in 50% of the patients with AD. Contrary to expectations, patients with semantic dementia also had hippocampal atrophy, which for the left side exceeded that seen in AD; other regions (temporal pole, parahippocampal gyrus, and lateral temporal lobe), spared in AD, were severely atrophied in this group. The patients with frontal variant FTD occupied an intermediate position and were largely indistinguishable from AD. Conclusions-Hippocampal atrophy is, therefore, not specific for AD. Semantic dementia can be distinguished from AD, by the presence of severe bilateral atrophy of the temporal pole, parahippocampal and lateral regions. These findings have implications for the diVerential diagnosis of dementias. (J Neurol Neurosurg Psychiatry 2001;70:165-173)