Can patients without early, prominent visual deficits still be diagnosed of posterior cortical atrophy?

BACKGROUND: Early and progressive disabling visual impairment is a core feature for the diagnosis of posterior cortical atrophy (PCA). However, some individuals that fulfil criteria over time might initially present with an onset of prominent posterior dysfunction other than visuoperceptual. METHODS: The clinical profile of five patients with a predominantly 'non-visual' posterior presentation (PCA2) was investigated and compared with sixteen individuals with visually predominant PCA (PCA1) and eighteen with typical amnestic Alzheimer disease (tAD). RESULTS: PCA2 patients showed significantly better performance than PCA1 in one visuospatial task and were free of Balint's syndrome and visual agnosia. Compared to tAD, PCA2 showed trends towards significantly lower performance in visuoperceptual tasks, more severe apraxia and more symptoms of Gerstmann's syndrome. CONCLUSIONS: Our sample of PCA2 patients did not present with clinically prominent visual symptoms but did show visual dysfunction on formal neuropsychological assessment (less pronounced than in PCA1 but more than in tAD) in addition to other posterior deficits. Broadening the definition of PCA to encompass individuals presenting with prominent 'non-visual' posterior dysfunction should be potentially considered in clinical and research contexts.

Neuropsychological correlates of whole brain atrophy in Alzheimer's disease.

Alzheimer's disease (AD) is associated with excess whole brain volume loss, and progressive cognitive impairment. We aimed to study the extent to which these two potential biomarkers of AD progression are correlated. Forty-six patients with sporadic AD were tested with a neuropsychometric battery including test of verbal and visual memory, vocabulary, arithmetic, naming, visuoperceptual skills and reasoning at two time-points, approximately 1 year apart; annualised rates of change for each test were calculated. Each subject also attended for up to twelve T1-weighted volumetric MRI scans at fixed intervals over a 2-year period. For each individual all possible scan-pairs were positionally registered, and whole brain atrophy rates were calculated using the brain boundary shift integral. Linear mixed models were used to investigate associations between atrophy rate and coincident change in each neuropsychometric score. Each model estimated the effect of a unit change in score, plus the additional effect of a fall to floor, after adjusting for baseline levels. 467 MRI scans were performed, permitting 2199 individual measures of change to be made. The model-derived mean atrophy rate was 2.23% per year with a between-subject SD of 0.99% per year. Increasing atrophy rate was significantly associated with rate of change in a number of non-memory based neuropsychological scores, with the strongest association seen with longitudinal change in matrix reasoning (p=0.004). These results provide further evidence that cerebral atrophy is a clinically relevant marker of AD progression. This methodology whereby data from patients falling to floor on a given test may be included and accounted for, rather than discarded, may find broader application in clinical studies incorporating neuropsychometric outcomes.

Development of selective verbal memory impairment secondary to a left thalamic infarct: a longitudinal case study.

A 68 year old man suffered an acute dysphasic episode with persistent memory disturbance while taking part as a control in a longitudinal magnetic resonance imaging (MRI) study. A small new left thalamic infarct involving the mamillo-thalamic tract could be demonstrated on volumetric MRI, coinciding with the development of a selective verbal memory impairment. This suggests that lateralisation of cognitive processing of visual and verbal material exists at the thalamic as well as the cortical level. High resolution volumetric MRI may be helpful in demonstrating small subcortical infarcts that may not be seen using computed tomography or conventional MRI.

A disorder of colour perception associated with abnormal colour after-images: a defect of the primary visual cortex.

A 64 year old woman with posterior cortical atrophy secondary to probable Alzheimer's disease is described. Her presenting symptom was of seeing objects as abnormally coloured after prior exposure to a coloured stimulus. Formal testing disclosed that the patient experienced colour after-images of abnormal latency, duration, and amplitude.The demonstration of prolonged colour after-images in a patient with a cortical disease process provides strong evidence that the generation of colour after-images is mediated at least in part by the visual cortex. A mechanism for the generation of colour after-images is proposed in which abnormal prolongation of the images results from excessive rebound inhibition of previously excited wavelength selective neurons in V1. This may occur as a consequence of the relative sparing of inhibitory interneurons in V1 in the context of the degeneration of excitatory neurons that occurs in Alzheimer's disease.

Refractory dyslexia: evidence of multiple task-specific phonological output stores.

We investigated the case of a patient whose reading was characterized by multiple phonemic paraphasic errors. An error analysis of a large corpus of reading responses (758 words, 86 non-words) highlighted the preponderance of phonological errors which did not occur in his naming, repetition or spontaneous speech. His comprehension of the written word was relatively preserved, even for words he was unable to read aloud. We suggest that his impairment lies at the level of the phonological output store. We also demonstrate that his reading performance was facilitated by increasing the response-stimulus delay. The strong influence of temporal factors is shown to be task-specific. Two main points are drawn from our results. First, we argue that our patient can be characterized as having a refractory access type of deficit; to our knowledge, no previous case of a refractory deficit affecting word reading has been reported. Secondly, the task specificity of both the phonological error pattern and the sensitivity to temporal factors is difficult to reconcile with the idea of a unitary phonological output store. Contrary to orthodox neuropsychological models, we propose that there are independent stores specific for reading and spoken output.

Acalculia: deficits of operational and quantity number knowledge.

We describe the standardization of three new tests of knowledge of quantity facts, number operations and multiplication facts. We also report a validation study in which a group of 50 patients with cortical degenerative disorders were tested on these three new tests of number processing. Our results show that the quantity facts and number operations tests are sensitive measures of number processing abilities. Performance on the three new tests and the Graded Difficulty Arithmetic (GDA) test were found to be significantly impaired in the Alzheimer's Disease (AD) group. The frontotemporal dementia (FTD) group was subdivided into those with a semantic dementia (SD) and those with prominent frontal features (Non-SD). The semantic dementia subgroup was more impaired than both the AD patient group and the nonsemantic FTD subgroup on the quantity facts test. A more fine grained analysis reveals several interesting patterns of performance, including a dissociation between impaired performance on the quantity facts and number operations tests and preserved performance on the GDA. The findings attest the value of comparing performance on the GDA and our new tests in delineating the nature of an individual's number processing deficits. Implications for the relation between simple arithmetic fact knowledge and higher level number processing are discussed.