Sian Thompson

Naming of objects, faces and buildings in mild cognitive impairment.

Accruing evidence suggests that the cognitive deficits in very early Alzheimers Disease (AD) are not confined to episodic memory, with a number of studies documenting semantic memory deficits, especially for knowledge of people. To investigate whether this difficulty in naming famous people extends to other proper names based information, three naming tasks - the Graded Naming Test (GNT), which uses objects and animals, the Graded Faces Test (GFT) and the newly designed Graded Buildings Test (GBT) - were administered to 69 participants (32 patients in the early prodromal stage of AD, so-called Mild Cognitive Impairment (MCI), and 37 normal control participants). Patients were found to be impaired on all three tests compared to controls, although naming of objects was significantly better than naming of faces and buildings. Discriminant analysis successfully predicted group membership for 100% controls and 78.1% of patients. The results suggest that even in cases that do not yet fulfil criteria for AD naming of famous people and buildings is impaired, and that both these semantic domains show greater vulnerability than general semantic knowledge. A semantic deficit together with the hallmark episodic deficit may be common in MCI, and that the use of graded tasks tapping semantic memory may be useful for the early identification of patients with MCI.

Is knowledge of famous people disproportionately impaired in patients with early and questionable Alzheimer's disease?

Twenty-two patients with early dementia of Alzheimers type (DAT) and 31 controls were administered tests of person-specific semantics (Experiment 1). DAT patients were impaired on all test components. In Experiment 2, 31 DAT patients, 28 questionable DAT (QDAT) patients, and 42 controls were administered the Graded Naming Test (GNT) and the newly designed Graded Faces Test (GFT), matched for difficulty with the GNT. DAT patients were impaired throughout but showed an advantage for naming objects over faces. The QDAT patients were impaired on the GFT only. Of the 7 QDAT patients who evolved to DAT within 1-2 years, 6 showed initial impairment on the GFT, whereas 17 of the nonconverters scored normally on the GFT. Results suggest greater and earlier vulnerability of person knowledge than general semantic knowledge in DAT.

Relapsing encephalopathy in a patient with α-methylacyl-CoA racemase deficiency

α-Methylacyl-CoA racemase (AMACR) deficiency is a rare disorder of fatty acid metabolism which has recently been described in three adult cases. We have identified a further patient with clinical features of a relapsing encephalopathy, seizures and cognitive decline over a 40 year period. Biochemical studies revealed grossly elevated plasma pristanic acid levels, and a deficiency of AMACR in skin fibroblasts. Sequence analysis of AMACR cDNA identified a homozygous point mutation (c154T>C). This case adds to the phenotypic variation seen in this peroxisomal disorder and highlights the importance of screening for plasma pristanic acid levels in patients with unexplained relapsing encephalopathies.

Is knowledge of famous people compromised in mild cognitive impairment

Objective: This study addressed the issue of whether person naming deficits in mild cognitive impairment (MCI) occurred with deficits in person semantic knowledge and whether person knowledge was more impaired than general semantics. Background: Recent definitions of MCI are beginning to encompass cognitive impairments outside the domain of episodic memory. Increasing evidence suggests that semantic memory may also be compromised in this patient group, including tasks of person naming and identification. Methods: Thirteen MCI patients and 14 control subjects matched for age and education performed parallel semantic batteries designed to probe person and general semantic knowledge. Results: On the person battery, the MCI patients demonstrated impairment relative to controls, on tasks of category fluency, naming, identification, verbal and nonverbal associative and sorting tasks, as well as matching names to faces. By contrast, on the general semantic battery impairments, they were impaired only on category fluency and the nonverbal sorting and associative tasks. A composite measure of person knowledge tasks was also sensitive to disease severity as measured by Mini-Mental State Examination. Conclusions: These results support the existence of deficits in MCI across various domains of person knowledge, and the suggestion that deterioration of unique semantic exemplars may be sensitive to incipient Alzheimer disease.

Utility of testing for apraxia and associated features in dementia

Introduction Existing literature suggests that the presence or absence of apraxia and associated parietal deficits may be clinically relevant in differential diagnosis of dementia syndromes. Aim This study investigated the profile of these features in Alzheimers disease (AD) and frontotemporal dementia (FTD) spectrum disorders, at first presentation. Methods Retrospective case note analysis was undertaken in 111 patients who presented to the Oxford Cognitive Disorders Clinic, Oxford, UK, including 29 amnestic AD, 12 posterior cortical atrophy (PCA), 12 logopenic primary progressive aphasia (lvPPA), 20 behavioural variant FTD (bvFTD), 7 non-fluent variant PPA (nfvPPA), 6 semantic variant PPA (svPPA) and 25 patients with subjective cognitive impairment (SCI). The clinical features of interest were: limb apraxia, apraxia of speech (AOS), and left parietal symptoms of dyslexia, dysgraphia, and dyscalculia. Results The prevalence of limb apraxia was highest in PCA, amnestic AD, lvPPA and nfvPPA. AOS was only observed in nfvPPA. Associated parietal features were more prevalent in AD spectrum than FTD spectrum disorders. Group comparisons between key differential diagnostic challenges showed that lvPPA and nfvPPA could be significantly differentiated on the presence of left parietal features and AOS, and amnestic AD could be differentiated from bvFTD, svPPA and SCI by limb apraxia. Regression analysis showed that limb apraxia could successfully differentiate between AD and FTLD spectrum disorders with 83% accuracy. Discussion Disease-specific profiles of limb apraxia and associated deficits can be observed. FTD and AD spectrum disorders can be difficult to differentiate due to overlapping cognitive symptoms, and measures of apraxia, in particular, appear to be a promising discriminator.

Memory Impairment at Initial Clinical Presentation in Posterior Cortical Atrophy

Posterior cortical atrophy (PCA) is characterized by core visuospatial and visuoperceptual deficits, and predominant atrophy in the parieto-occipital cortex. The most common underlying pathology is Alzheimers disease (AD). Existing diagnostic criteria suggest that episodic memory is relatively preserved. The aim of this study was to examine memory performance at initial clinical presentation in PCA, compared to early-onset AD patients (EOAD). 15 PCA patients and 32 EOAD patients, and 34 healthy controls were entered into the study. Patients were tested on the Addenbrookes Cognitive Examination (ACE-R), consisting of subscales in memory and visuospatial skills. PCA and EOAD patients were significantly impaired compared to controls on the ACE total score (p < 0.001), visuospatial skills (p < 0.001), and memory (p < 0.001). Consistent with the salient diagnostic deficits, PCA patients were significantly more impaired on visuospatial skills compared to EOAD patients (p < 0.001). However, there was no significant difference between patient groups in memory. Further analysis of learning, recall, and recognition components of the memory subscale showed that EOAD and PCA patients were significantly impaired compared to controls on all three components (p < 0.001), however, there was no significant difference between EOAD and PCA patients. The results of this study show that memory is impaired in the majority of PCA patients at clinical presentation. The findings suggest that memory impairment must be considered in assessment and management of PCA. Further study into memory in PCA is warranted, since the ACE-R is a brief screening tool and is likely to underestimate the presence of memory impairment.

Relapsing encephalopathy in a patient with α-methylacyl-CoA racemase deficiency.

&agr;-Methylacyl-CoA racemase (AMACR) deficiency is a rare disorder of fatty acid metabolism which has recently been described in three adult cases. We have identified a further patient with clinical features of a relapsing encephalopathy, seizures and cognitive decline over a 40 year period. Biochemical studies revealed grossly elevated plasma pristanic acid levels, and a deficiency of AMACR in skin fibroblasts. Sequence analysis of AMACR cDNA identified a homozygous point mutation (c154T>C). This case adds to the phenotypic variation seen in this peroxisomal disorder and highlights the importance of screening for plasma pristanic acid levels in patients with unexplained relapsing encephalopathies.

Association between precuneus volume and autobiographical memory impairment in posterior cortical atrophy: Beyond the visual syndrome.

Posterior cortical atrophy is a neurodegenerative syndrome characterised by progressive disruption of visual and perceptual processing, associated with atrophy in the parieto-occipital cortex. Current diagnostic criteria describe relative sparing of episodic memory function, but recent findings suggest that anterograde memory is often impaired. Whether these deficits extend to remote memory has not been addressed. A large body of evidence suggests that the recollection of an autobiographical event from the remote past coincides with the successful retrieval of visual images. We hypothesised that the profound visual processing deficits in posterior cortical atrophy would result in impaired autobiographical memory retrieval. Fourteen posterior cortical atrophy patients, eighteen typical Alzheimers disease patients and twenty-eight healthy controls completed the Autobiographical Interview. Autobiographical memory in posterior cortical atrophy was characterised by a striking loss of internal, episodic detail relative to controls and to same extent as typical Alzheimers disease patients, in conjunction with an increase in external details tangential to the memory described. The memory narratives of posterior cortical atrophy patients showed a specific reduction in spatiotemporal and perceptual detail. Voxel-based morphometry analysis revealed atrophy of the parieto-occipital cortices in posterior cortical atrophy but relatively spared hippocampi bilaterally, compared with characteristic atrophy of the medial temporal lobes in typical Alzheimers disease. Analysis of brain regions showing posterior cortical atrophy-specific atrophy revealed a correlation between perceptual details in autobiographical memory and grey matter density in the right precuneus. This study demonstrates remote memory impairment in posterior cortical atrophy despite relatively preserved medial temporal lobe structures. The results demonstrate, for the first time, profound autobiographical memory impairment in PCA and suggest that this is driven by the well-recognised deficits in higher-order visual processing. The findings are discussed in the context of posterior parietal contributions to imagery and memory, and the clinical implications of autobiographical memory impairment for diagnostic and management protocols in posterior cortical atrophy.

Lateral parietal contributions to memory impairment in posterior cortical atrophy

Objective Posterior cortical atrophy (PCA) is a neurodegenerative syndrome characterised by progressive impairment in visuospatial and perceptual function. Recent findings show that memory functioning can also be compromised early in the course of disease. In this study, we investigated the neural basis of memory impairment in PCA, and hypothesised that correlations would be observed with parietal cortex rather than classic medial temporal memory structures. Methods Eighteen PCA patients, 15 typical Alzheimers disease (tAD) patients and 21 healthy controls underwent memory testing with the Rey Auditory Verbal Learning Test (RAVLT) word list and MRI. Voxel-based morphometry (VBM) was used to identify regions in the parietal and medial temporal lobes that correlated with memory performance. Results Compared with controls, PCA patients were impaired at learning, immediate and delayed recall and recognition of the RAVLT. Learning rate and immediate recall was significantly better in PCA compared to tAD, whereas there was no difference in delayed recall. Recognition memory also was not statistically different between patient groups, but PCA patients made significantly more false positive errors than tAD patients. VBM analysis in the PCA patients revealed a significant correlation between total learning and grey matter density in the right supramarginal gyrus, right angular gyrus and left postcentral gyrus. The left post central gyrus also significantly correlated with immediate and delayed recall and with recognition memory. No correlations were detected in the medial temporal lobe. Conclusions The findings provide novel evidence that early verbal memory impairment is frequently observed in PCA, and is associated with damage to lateral parietal structures. The results have implications for the diagnosis and management of PCA.

12 Characterising remote memory in posterior cortical atrophy

Objective Posterior cortical atrophy (PCA) is a syndrome characterised by progressive disruption of visual processing and neurodegeneration in the parieto-occipital cortex. The most common underlying cause is Alzheimer’s pathology. Anterograde memory function and the medial temporal lobes (MTLs) are thought to be relatively preserved. Given that the typical pattern of atrophy in PCA overlaps with brain networks critical for the recollection of personal events, we hypothesised that patients would be impaired on a test of autobiographical memory. Method 14 PCA, 18 Alzheimer’s disease (AD) patients and 28 healthy controls completed the Autobiographical Interview. Results Both PCA and AD patients produced significantly less internal detail relevant to the chosen memories, compared with controls. However, the PCA group also produced a significantly greater amount of unrelated external detail compared with controls and AD. Across the lifespan, PCA and AD again showed similarly poor recall of relevant remote memory details compared with controls, with no temporal gradient evident in either group. Correlational analysis in PCA patients revealed a significant relationship between total external details and the Hayling test of inhibitory control, and a trend towards significance between internal details and visual imagery. Conclusion Our findings suggest that, despite relatively preserved MTL structures, PCA patients have significantly impaired remote memory. We propose that damage to posterior regions of the brain disrupts access to visual information integral to the autobiographical memory trace. Increased provision of external details may be a compensatory strategy due to lack of access to details relevant to episodic memories.