Nuclear carrier and RNA-binding proteins in frontotemporal lobar degeneration associated with fused in sarcoma (FUS) pathological changes.

AIMS: We aimed to investigate the role of the nuclear carrier and binding proteins, transportin 1 (TRN1) and transportin 2 (TRN2), TATA-binding protein-associated factor 15 (TAF15) and Ewing's sarcoma protein (EWS) in inclusion body formation in cases of frontotemporal lobar degeneration (FTLD) associated with fused in sarcoma protein (FTLD-FUS). METHODS: Eight cases of FTLD-FUS (five cases of atypical FTLD-U, two of neuronal intermediate filament inclusion body disease and one of basophilic inclusion body disease) were immunostained for FUS, TRN1, TRN2, TAF15 and EWS. Ten cases of FTLD associated with TDP-43 inclusions served as reference cases. RESULTS: The inclusion bodies in FTLD-FUS contained TRN1 and TAF15 and, to a lesser extent, EWS, but not TRN2. The patterns of immunostaining for TRN1 and TAF15 were very similar to that of FUS. None of these proteins was associated with tau or TDP-43 aggregations in FTLD. CONCLUSIONS: Data suggest that FUS, TRN1 and TAF15 may participate in a functional pathway in an interdependent way, and imply that the function of TDP-43 may not necessarily be in parallel with, or complementary to, that of FUS, despite each protein sharing many similar structural elements.

Arithmetic knowledge in semantic dementia: is it invariably preserved?

There is accumulating evidence of preserved arithmetic knowledge in semantic dementia (SD), contrasting with patients' striking impairment in other domains of semantic memory. This important finding exemplifies domain specificity in the breakdown of semantic memory and supports notions of the functional independence of semantic number knowledge. Nevertheless, evidence for preserved arithmetic knowledge in SD comes largely from single case studies. It is not known whether such preservation is a universal finding, or whether it persists irrespective of disease severity. The present study examined performance of 14 SD patients, varying in the severity of their semantic impairment, on tasks assessing knowledge of arithmetic signs, and on single-digit and multi-digit calculation problems, permitting evaluation of fact retrieval and use of procedures. SD patients performed generally well compared to 10 healthy controls on tests of addition and subtraction. However, abnormalities were elicited, which were not explained by education or hemispheric side of atrophy, but increased as a function of semantic severity. Patients had difficulty identifying arithmetic signs. They used increasingly basic, inflexible strategies to retrieve multiplication table 'facts', and in multi-digit calculations they made procedural errors that pointed to a failure to understand the differential weighting of left and right hand columns. The pattern of responses and error types mirrors in reverse that found in children as they acquire arithmetic competence, and suggests a progressive degradation in conceptual understanding of arithmetic. Longitudinal study of two SD patients demonstrated an association between semantic decline and impaired arithmetic performance. The findings challenge the notion of arithmetic knowledge as a totally separate semantic domain and suggest that the temporal lobes play an important role in arithmetic understanding.

Emotion recognition in Huntington's disease and frontotemporal dementia.

A well-documented feature of Huntington's disease (HD) is disproportionate impairment in the ability to recognise the emotional expression of disgust. However, this finding has been challenged by studies that report no differential disgust impairment and attribute apparent differences across emotions to task difficulty. The present study sought to shed light on disparities in findings through a comparative study of emotion recognition in HD and frontotemporal dementia (FTD). Ten HD, 12 FTD patients and 12 healthy controls were administered 10 tasks assessing facial and vocal recognition of emotions and comprehension of emotion terms. The findings were not consistent with either the 'selective disgust impairment' or 'task difficulty' view. Both HD and FTD groups were impaired compared to controls, deficits in HD being less severe. Impairments in FTD were elicited for all emotions whereas in HD they were demonstrated predominantly for negative emotions of fear, disgust and anger. Consistency in performance, despite varying task demands, excluded an explanation in terms of item difficulty, and was in keeping with the notion of distinct neural substrates for processing of negative emotions. Contrary to the notion of disproportionate disgust impairment, the most severe deficits in HD were elicited for anger, a finding that may have relevance for the poor anger control that is the hallmark of HD. The data raise the possibility that linguistic influences and conceptual complexities of the emotion of disgust may contribute to the variable finding of selective disgust impairment in HD.

Imbalance of a serotonergic system in frontotemporal dementia: implication for pharmacotherapy.

RATIONALE: Information is sparse on neurotransmitter deficiencies in frontotemporal dementia (FTD), in particular with reference to distinct histological subgroups and Alzheimer's disease (AD). OBJECTIVES: To evaluate in FTD with the major histologies, and compare with AD and controls, neurotransmission indices, as these may help in developing treatment. MATERIALS AND METHODS: Post-mortem grey matter from Brodmann Area 21, 9 and 7 of 51 brains was assayed for ten neurochemical parameters indexing neurotransmission. Repeated measures analyses of variance were carried out for each parameter comparing groups (FTD vs AD vs control) at each anatomical site. RESULTS: In FTD only the indices of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid, serotonin (5-HT)(1A) and 5-HT(2A) receptors were significantly reduced from control values. Of the ten parameters only 5-HT(1A) receptors showed significant group x site interaction. This reflected disproportionate reduction in frontal and temporal compared to parietal cortex. In FTD three other receptors (muscarinic, M(1), N-methyl-D: -aspartate, NMDA, and kainate), choline acetyltransferase (ChAT) activity, 5-HT and 5-hydroxyindoleacetic acid content and 5-HT reuptake site values were not significantly reduced from control values. Only 5-HT, 5-HT reuptake site and ChAT values were significantly higher in FTD than AD. NMDA receptor and ChAT values were significantly reduced from control only in AD. CONCLUSIONS: Neurochemical results in FTD indicate degeneration and loss of pyramidal neurones in frontotemporal neocortex, yet 5-HT afferents and 5-HT concentration, which are inhibitory on pyramidal neurones, were relatively preserved. This could lead to an excess of extraneural 5-HT causing underactivity of surviving pyramidal neurones. Pharmacotherapy with a 5-HT(1A) receptor antagonist may be indicated.

Accuracy of single-photon emission computed tomography in differentiating frontotemporal dementia from Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) and frontotemporal dementia (FTD) are the commonest causes of presenile dementia. In the absence of a biological marker, diagnosis is reliant on clinical evaluation. Confirmation is often sought from neuroimaging, including single-photon emission computed tomography (SPECT). Most previous SPECT studies lack pathological validation. AIM: To examine the accuracy of SPECT in differentiating FTD from AD in patients with subsequent pathological confirmation. METHODS: Technetium-99-labelled hexamethyl propylene amine oxime SPECT images obtained at initial evaluation in 25 pathologically confirmed cases of FTD were examined. These images were visually rated by an experienced blinded nuclear medicine consultant and compared with those of 31 patients with AD, also with pathological validation. RESULTS: A reduction in frontal cerebral blood flow (CBF) was more common in FTD and was of diagnostic value (sensitivity 0.8, specificity 0.65 and likelihood ratio (LR) 2.25; 95% CI 1.35 to 3.77). A pattern of bilateral frontal CBF reduction without the presence of associated bilateral parietal CBF change is diagnostically more accurate (sensitivity 0.80, specificity 0.81 and +LR 4.13, 95% CI 1.96 to 8.71). Diagnostic categorisation (FTD or AD) on the basis of SPECT alone was less accurate than clinical diagnosis (based on neurology and detailed neuropsychological evaluation). One patient with FTD was initially clinically misdiagnosed as AD, owing to the lack of availability of full neuropsychological assessment. However, SPECT correctly diagnosed this patient, providing a diagnostic gain of 4%. CONCLUSION: Technetium-99-labelled hexamethyl propylene amine oxime SPECT CBF patterns provide valuable information in the diagnosis of FTD and AD. These data can be better used as an adjunct to clinical diagnosis if pathology is to be correctly predicted in life.

Inferring thought and action in motor neurone disease.

The traditional assumption that classical motor neurone disease (MND) invariably spares cognitive function is now recognised to be incorrect. Deficits have most commonly been demonstrated on executive tasks suggesting impaired function of frontal systems. Yet, crucial aspects of frontal lobe function have not hitherto been explored. The study used tests of theory of mind (ToM) (interpretation of cartoons and stories) to examine the ability of 16 patients with MND to interpret social situations and ascribe mental states to others. Only minor differences were elicited in the MND group as a whole compared to controls, and performance was not differentially affected for cartoons and stories requiring inference of another's mental state (mental) compared to control (physical) cartoons and stories. However, abnormalities were elicited on both mental and physical tasks in a subgroup of patients with bulbar signs. Moreover, examination of individual patient scores revealed a spectrum of performance ranging from normal to severely impaired. Errors were qualitatively similar to those seen in frontotemporal dementia (FTD). Performance on the ToM tasks was significantly correlated with conventional, untimed measures of executive function, suggesting that ToM deficits in MND are likely to be linked to a more general executive failure. The findings contribute to the understanding of ToM performance in neurodegenerative disease and provide further evidence of the association between MND and FTD.

Progranulin gene mutations associated with frontotemporal dementia and progressive non-fluent aphasia.

Frontotemporal lobar degeneration (FTLD) refers to a focal, non-Alzheimer form of cerebral degeneration that encompasses the distinct clinical syndromes of frontotemporal dementia (FTD), progressive non-fluent aphasia (PNFA) and semantic dementia. Some patients show tau-based pathological changes and in familial cases mutations have been identified in the microtubule-associated protein tau gene (MAPT) on chromosome 17q21. However, many cases are tau-negative, showing instead ubiquitin-immunoreactive (UBQ-ir) neuronal cytoplasmic inclusions and neurites, and in some familial cases UBQ-ir neuronal intranuclear inclusions of a lentiform appearance. Very recently, mutations have been identified in familial cases in the progranulin (PGRN) gene, also on chromosome 17q21. Clinical, pathological and molecular diversity within FTLD highlights the importance of careful examination of clinical-pathological-genetic relationships. This paper reports, for the first time, a clinico-pathological investigation of two FTLD families with PGRN mutations, and compares the clinical characteristics with those of patients studied in the department with MAPT mutations. The clinical profile associated with PGRN mutations constituted, in some patients, a prototypical picture of FTD and in others one of PNFA, both profiles occurring within the same family. Patients with PGRN mutations exhibited phonological deficits, whereas in patients with MAPT mutations language abnormalities, when present in addition to the prominent behavioural disorder, take the form of semantic disturbance. The findings provide compelling evidence for the link between FTD and PNFA, while raising the possibility of identifiable clinical differences between FTLD patients with MAPT and PGRN mutations.

Genetic associations between cathepsin D exon 2 C-->T polymorphism and Alzheimer's disease, and pathological correlations with genotype.

Genetic variations represent major risk factors for Alzheimer's disease (AD). While familial early onset AD is associated with mutations in the amyloid precursor protein and presenilin genes, only the e4 allele of the apolipoprotein E (APOE) gene has so far been established as a genetic risk factor for late onset familial and sporadic AD. It has been suggested that the C-->T (224Ala-->Val) transition within exon 2 of the cathepsin D gene (CTSD) might represent a risk factor for late onset AD. The objective of this study was to investigate whether possession of the CTSD exon 2 T allele increases the risk of developing AD, and to determine whether this modulates the amyloid pathology of the disease in conjunction with, or independent of, the APOE e4 allele. Blood samples were obtained from 412 patients with possible or probable AD and brain tissues from a further 148 patients with AD confirmed by postmortem examination. CTSD and APOE genotyping were performed by PCR on DNA extracted from blood, or from frontal cortex or cerebellum in the postmortem cases. Pathological measures of amyloid beta protein (Abeta), as plaque Abeta40 and Abeta42(3) load and degree of cerebral amyloid angiopathy were made by image analysis or semiquantitative rating, respectively. CTSD genotype frequencies in AD were not significantly different from those in control subjects, nor did these differ between cases of early or late onset AD or between younger and older controls. There was no gene interaction between the CTSD T and APOE e4 alleles. The amount of plaque Abeta40 was greater in patients carrying the CTSD T allele than in non-carriers, and in patients bearing APOE e4 allele compared with non-carriers. Possession of both these alleles acted synergistically to increase levels of plaque Abeta40, especially in those individuals who were homozygous for the APOE e4 allele. Possession of the CTSD T allele had no effect on plaque Abeta42(3) load or degree of CAA. Possession of the CTSD T allele does not increase the risk of developing AD per se, but has a modulating effect on the pathogenesis of the disorder by increasing, in concert with the APOE e4 allele, the amount of Abeta deposited as senile plaques in the brain in the form of Abeta40.

The apolipoprotein E epsilon4 allele selectively increases the risk of frontotemporal lobar degeneration in males.

OBJECTIVE: To determine whether polymorphic variations in the apolipoprotein E gene (APOE) are associated with increased risk of frontotemporal lobar degeneration (FTLD) when mutation in tau gene is absent. METHODS: The APOE gene was genotyped by polymerase chain reaction from DNA routinely extracted from blood or brain tissues. The APOE epsilon4 allele frequency in 198 patients with FTLD not associated with mutations in tau gene was compared with that of a control group of 756 normal individuals drawn from the same geographical region. Analyses were done according to clinical subtype or sex. RESULTS: The APOE epsilon4 allele frequency (19.4%) was increased (p = 0.01) in FTLD v the whole control group (14.1%), while the APOE epsilon2 allele frequency in FTLD (6.5%) was slightly lower than in controls (8.0%) (NS). The APOE epsilon4 allele frequency in men with FTLD (22.3%) was greater (p = 0.002) than in male controls (12.3%); the frequency in women (16.3%) was similar to that in female controls (14.8%) (NS). The APOE epsilon2 allele frequency in men with FTLD was 4.9% while in male controls it was 9.5% (p = 0.06), but there was no difference in women (7.5% v 7.9%, NS). Neither the APOE epsilon2 nor APOE epsilon4 allele frequency varied significantly between any of the clinical subtypes. CONCLUSIONS: In FTLD not associated with mutations in tau gene, possession of APOE epsilon4 allele in men roughly doubles the chances of developing disease, whereas this has no impact upon disease risk in women.

Primary angiitis of the central nervous system: emerging variants.

BACKGROUND: Primary angiitis of the central nervous system (PACNS), a serious disease, has not featured prominently in the spectrum of multi-organ disease seen in vasculitis clinics. AIM: To evaluate the presentation, natural history and features of PACNS variants and compare to those of systemic vasculitides. DESIGN: Retrospective analysis. METHODS: Patients (n=105) presented during 1988-2003 to a tertiary regional vasculitis clinic receiving unselected disease types. Data were collected from a clinical database, patient and laboratory records. RESULTS: The frequency of PACNS presentation rose over the study period, compared with most of the other vasculitides. When PACNS was divided into small- and middle-sized vessel disease (SVD/MVD), their clinical courses differed substantially. SVD PACNS was responsive to immunosuppressive drugs, but relapsed during prolonged periods in all patients on maintenance immunosuppressives, or after withdrawal of treatment, causing recurrent, severe and irreversible CNS injury. MVD PACNS had isolated episodes at presentation, with a paucity of relapses during prolonged follow-up. DISCUSSION: Similarities between SVD PACNS and microscopic polyarteritis suggest the former may represent a limited form of the latter. MVD PACNS has a distinctly more benign relapse pattern than its multisystem counterpart polyarteritis nodosa. Acute-phase serology was useful in designating inflammatory processes at presentation of patients presenting with encephalopathy caused by SVD only, but were unhelpful in defining relapses in this form of PACNS, the definition of which in all cases rested on clinical assessment and MR scanning. Direct cerebral angiography was not diagnostic in any case of SVD PACNS; positive brain biopsy is diagnostically unequivocal, but the total clinical syndrome with imaging may establish a diagnosis with highest probability. In MVD PACNS, angiography with MR scan proved diagnostic. We suggest an algorithm for a rational, minimally invasive approach to investigation. In PACNS, SVD and MVD are important variants, and decisions about therapy should incorporate these distinctions.

Qualitative neuropsychological performance characteristics in frontotemporal dementia and Alzheimer's disease.

BACKGROUND: Frontotemporal dementia (FTD) and Alzheimer's disease are clinically distinct disorders, yet neuropsychological studies have had variable success in distinguishing them. A possible reason is that studies typically rely on overall accuracy scores, which may obscure differences in reasons for failure. OBJECTIVES: To explore the hypothesis that analysis of qualitative performance characteristics and error types, in addition to overall numerical scores, would enhance the neuropsychological distinction between FTD and Alzheimer's disease. METHODS: 38 patients with FTD and 73 with Alzheimer's disease underwent assessment of language, visuospatial abilities, memory, and executive function, using a neuropsychological screening instrument and standard neuropsychological tests. In each of these cognitive domains, performance characteristics and error types were documented, in addition to numerical scores on tests. RESULTS: Whereas comparison of neuropsychological test scores revealed some group differences, these did not occur consistently across tests within cognitive domains. However, analysis of performance characteristics and error types revealed qualitative differences between the two groups. In particular, FTD patients displayed features associated with frontal lobe dysfunction, such as concrete thought, perseveration, confabulation, and poor organisation, which disrupted performance across the range of neuropsychological tests. CONCLUSIONS: Numerical scores on neuropsychological tests alone are of limited value in differentiating FTD and Alzheimer's disease, but performance characteristics and error types enhance the distinction between the two disorders. FTD is associated with a profound behavioural syndrome that affects performance on cognitive assessment, obscuring group differences. Qualitative information should be included in neuropsychological research and clinical assessments.

Autopsy proven sporadic frontotemporal dementia due to microvacuolar-type histology, with onset at 21 years of age.

We describe the clinical, neuropsychological, and neuropathological features of a 21 year old woman with frontotemporal dementia (FTD). The early presentation was of florid behavioural change involving hyperactivity and disinhibition. Magnetic resonance imaging and single photon emission computed tomography of the brain revealed atrophy and severe functional abnormalities of the frontal and temporal lobes, respectively. Electroencephalogram was normal. At autopsy, there was gross frontotemporal brain atrophy and the underlying histology was of a microvacuolar-type degeneration; no tau or ubiquitin immunoreactive, intraneuronal inclusions were seen. There was no family history of dementia and no mutation in the tau gene. We believe this patient represents the youngest (so far) recorded case of FTD associated with this particular histological form of the disorder.

Knowledge of famous faces and names in semantic dementia.

Semantic dementia is a focal clinical syndrome, resulting from degeneration of the temporal lobes and characterized by progressive loss of conceptual knowledge about the world. Because of the highly circumscribed nature of the disorder it is a natural model for improving understanding of how semantic information is cerebrally represented. There is currently a lack of consensus. One view proposes the existence of modality specific meaning systems, in which visual and verbal information are stored separately. An opposing view assumes that information is represented by a unitary, amodal semantic system. The present study explores these alternatives in an examination of famous face and name knowledge in 15 patients with semantic dementia. The study of face recognition in patients with an established semantic disorder also permits an examination of the relationship between semantic dementia and the focal clinical syndrome of progressive prosopagnosia. The semantic dementia patients were profoundly impaired on both face and name identification and familiarity judgement tasks compared with amnesic patients with Alzheimer's disease and healthy controls. However, whereas the two reference groups performed better for names than faces, the semantic group showed the opposite pattern. This overall profile masked individual differences: semantic dementia patients with predominant left temporal lobe atrophy showed better recognition of names than faces, whereas patients with right temporal predominance showed the reverse pattern. Relative superiority for names or faces was mirrored by corresponding superiority for words or pictures on a standard semantic test. We interpret the findings as inconsistent with a unitary, amodal model of semantic memory. However, the data are not wholly compatible with a strict multiple system account. The data favour a model of semantic memory comprising a single interconnected network, with dedicated brain regions representing modality specific information. The data emphasize the importance of the anterior, inferolateral parts of the left temporal lobe for the representation of names and the corresponding parts of the right temporal lobe for faces. Dissociations between face and name knowledge provide a challenge for existing models of face processing. Moreover, they lead us to argue that the focal syndrome of progressive prosopagnosia is one of the clinical presentations of semantic dementia and not a separate clinical entity.

Social cognition in frontotemporal dementia and Huntington's disease.

Frontotemporal dementia (FTD) and Huntington's disease (HD) are degenerative disorders, with predominant involvement, respectively of frontal neocortex and striatum. Both conditions give rise to altered social conduct and breakdown in interpersonal relationships, although the factors underlying these changes remain poorly defined. The study used tests of theory of mind (interpretation of cartoons and stories and judgement of preference based on eye gaze) to explore the ability of patients with FTD and HD to interpret social situations and ascribe mental states to others. Performance in the FTD group was severely impaired on all tasks, regardless of whether the test condition required attribution of a mental state. The HD group showed a milder impairment in cartoon and story interpretation, and normal preference judgements. Qualitative differences in performance were demonstrated between groups. FTD patients made more concrete, literal interpretations, whereas HD patients were more likely to misconstrue situations. The findings are interpreted as demonstrating impaired theory of mind in FTD, as one component of widespread executive deficits. In HD the evidence does not suggest a fundamental loss of theory of mind, but rather a tendency to draw faulty inferences from social situations. It is concluded that social breakdown in FTD and HD may have a different underlying basis and that the frontal neocortex and striatum have distinct contributions to social behaviour.

Distinct neuropsychological characteristics in Creutzfeldt-Jakob disease.

OBJECTIVES: To characterise the nature of cognitive change in Creutzfeldt-Jakob disease (CJD). METHODS: Case histories are reported of four patients with sporadic (sCJD) and two with familial CJD (fCJD), with postmortem pathological findings in four cases. The data derived from cognitive examination are examined with respect to the presence or absence of a variety of characteristics to elicit performance profiles across cognitive domains. RESULTS: Three patients with sCJD exhibited clear focal cortical deficits. One patient had visual impairment leading to cortical blindness, associated with posterior hemisphere abnormalities on single photon emission computed tomography (SPECT) imaging; two others had impairments in language, mirrored by left hemisphere SPECT abnormalities. The remaining three patients showed no specific cortical symptomatology. Despite these differences all six patients shared common qualitative characteristics: episodic unresponsiveness, interference effects, and profound verbal and motor perseveration. These common features are interpreted in terms of impaired activation and regulation of neocortex from subcortical structures. Findings from postmortem pathological examination and from the published literature provide converging evidence to implicate a critical role of the thalamus. CONCLUSION: These preliminary findings suggest that sCJD and fCJD may be associated with distinct neuropsychological characteristics.

Diagnostic value of high signal abnormalities on T2 weighted MRI in the differentiation of Alzheimer's, frontotemporal and vascular dementias.

OBJECTIVE: The occurrence of high signal abnormalities on T2 weighted images is strongly age related. The diagnostic value of these changes in a younger population with dementia is not currently known. We studied the potential of high signal changes on magnetic resonance imaging (MRI) in differentiating Alzheimer's disease (AD), frontotemporal dementia (FTD) and vascular dementia (VaD) in younger patients. METHODS: High signal abnormalities were rated, using a previously validated scale, from hard copies of T2 weighted axial images of 102 patients with AD (n=49), VaD (n=31), FTD (n=22) (mean ages 63-65 years). RESULTS: High signal abnormalities were widespread across AD, VaD and FTD. Although they were most frequent and most severe in the VaD group only lacunes and grade III deep white matter hyperintensities (DWMH) were specific for these patients. CONCLUSIONS: High signal changes on T2 weighted images on MRI are common across degenerative (AD and FTD) and vascular dementias. Although lacunes and grade III DWMH are specific for VaD, the low sensitivities (sensitivities: for lacunes, 0.32; for grade III DWMH, 0.16) limit their use as diagnostic markers for VaD. High signal changes on MRI should be interpreted with caution in dementias. Their presence, even in younger patients, should not deter one from diagnosing AD or FTD.

Psychomotor, executive, and memory function in preclinical Huntington's disease.

The earliest changes in the development of Huntington's disease (HD) remain controversial. Studies of cognitive function in preclinical individuals who have the HD mutation have yielded contradictory results. This study compared cognitive and motor performance in 51 people with the HD mutation who had no clinical signs of HD, 85 at-risk individuals without the HD mutation and 43 individuals in the early stages of HD. Whereas highly significant differences were detected between the preclinical and early-HD groups, only subtle impairments were present in at-risk individuals with the HD mutation compared to those with normal HD alleles, principally for low-demand psychomotor tasks. Complementing these observations, longitudinal investigation showed that performance on psychomotor tasks in people with the mutation who were close to clinical onset of HD was intermediate between that of individuals many years from onset and those in the early stages of HD, suggesting a slowly insidious evolution of deficit. In contrast, memory performance showed a more precipitous decline around the time of clinical onset of HD. The findings, which suggest that HD patients' functional deficits do not evolve uniformly, help to resolve some of the disparities in the literature on preclinical HD.

Qualitative performance characteristics differentiate dementia with Lewy bodies and Alzheimer's disease.

OBJECTIVES: To determine whether dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) can be differentiated on the basis of qualitative performance characteristics during neuropsychological evaluation. METHODS: Forty one patients with clinically defined DLB were matched with 26 patients with AD for age, illness duration, nature and severity of cognitive deficits, and regional blood flow distribution on SPECT. The presence or absence of a set of qualitative performance characteristics, observed and recorded during the patients' initial cognitive evaluation, was identified by retrospective analysis of patients' records and the groups compared. RESULTS: Inattention, visual distractibility, impairments in establishing and shifting mental set, incoherence, confabulatory responses, perseveration, and intrusions were significantly more common in DLB than AD. Intrusions were particularly common in DLB, occurring in 78% of the group. They included externally cued intrusions arising from the visual environment, a feature never seen in AD. In a stepwise logistic regression analysis impaired mental set shifting, perseveration, and the presence of intrusions correctly classified 79% of patients. CONCLUSION: It is possible to differentiate DLB and AD on the basis of qualitative features of performance. As many features are amenable to detection at clinical interview, they ought to contribute to clinicians' diagnostic armoury, leading to improved clinical recognition of DLB.