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Neuropathological examination of both individuals in a monozygotic (MZ) twin pair with Alzheimer's disease (AD) is rare, especially in the molecular genetic era. We had the opportunity to assess the concordance and discordance of clinical presentation and neuropathology in three MZ twin pairs with AD.The MZ twins were identified and characterised by the University of Washington Alzheimer's Disease Research Center. We reviewed the available clinical and neuropathological records for all six cases looking specifically for concordance and discordance of clinical phenotype, neuritic amyloid plaques (NP), neurofibrillary tangles (NFT) and Lewy related pathology (LRP).Discordance in age of onset for developing AD in the MZ twins varied from 4 to 18 years. Clinical presentations also differed between twins. One twin presented with a dementia with Lewy Body clinical syndrome while the other presented with typical clinical AD. Neuropathology within the MZ twin pairs was concordant for NP and NFT, regardless of duration of disease, and was discordant for LRP. This difference was most marked in the late onset AD twin pair. One pair was found to have a mutation in presenilin-1 (PS1) (A79V) with remarkably late onset in a family member.MZ twins with AD can vary considerably in age of onset, presentation and disease duration. The concordance of NP and NFT pathological change and the discordance of LRP support the concept that, in AD, the former are primarily under genetic control whereas the latter (LRP) is more influenced by disease duration and environmental factors. The A79V mutation in PS1 can be associated with very late onset of dementia.

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.

Background: Olfactory dysfunction is common in old age, but its basis is uncertain. Objective: To test the hypothesis that difficulty in identifying odours in old age is related to the accumulation of Alzheimer’s disease pathology. Methods: As part of the Rush Memory and Aging Project, participants completed the 12-item Brief Smell Identification Test, a standard measure of odour identification. During a mean (standred deviation (SD)) of 2.2 (1.2) years of follow-up (range 0.2–4.9), 166 people died, with brain autopsies performed on 129 (77.7%) people and neuropathological examinations completed on 77 (mean (SD) age at death 87.5 (5.9) years; median postmortem interval 6.1 h). From a uniform postmortem examination of multiple brain regions, summary measures of plaque and tangle pathology were derived on the basis of silver staining, and those of amyloid β burden, tangle density and Lewy bodies on the basis of immunohistochemistry. Results: Odour identification performance ranged from 0 to 12 correct (mean (SD) 8.0 (2.6)). In analyses adjusted for age, sex and education, a composite measure of plaques and tangles accounted for >12% of the variation in odour identification. The association remained after controlling for dementia or semantic memory. Density of τ tangles was inversely related to odour identification. A similar effect for amyloid burden was attenuated after controlling for tangles. The association with odour identification was robust for tangles in the entorhinal cortex and CA1/subiculum area of the hippocampus, but not for tangles in other cortical sites. Lewy bodies, identified in 12.5%, were not related to odour identification, probably partly due to to their relative infrequency. Conclusion: The results suggest that difficulty in identifying familiar odours in old age is partly due to the accumulation of neurofibrillar pathology in central olfactory regions.

Objective: To assess the associations of medial temporal lobe atrophy (MTA) and white matter hyperintensities (WMH) with cognitive function in a large group of independently functioning elderly people. Methods: Data were drawn from the multicentre, multinational leukoaraiosis and disability (LADIS) project which is studying prospectively the role of WMH as an independent predictor of the transition to disability in non-disabled elderly people. In all, 639 participants were enrolled in the LADIS study. For the present analysis, data on 581 subjects were available. Cognitive function was assessed by the mini-mental state examination (MMSE). Visual ratings of WMH and MTA were undertaken on magnetic resonance images (MRI). Results: The presence of either severe WMH or MTA was associated with a modest but non-significant increase in frequency of mild cognitive deficits (severe WMH: odds ratio (OR) = 1.9 (95% confidence interval (CI), 1.0 to 3.7); MTA present: OR = 1.5 (95% CI, 0.8 to 2.8)). However, subjects with the combination of MTA and severe WMH had a more than fourfold increase in frequency of mild cognitive deficits (OR = 4.1 (95% CI, 2.3 to 7.4)). Analysis of variance with post hoc Bonferroni t tests showed that subjects with both MTA and severe WMH performed worse on MMSE than those with either no MRI abnormality or a single MRI abnormality (p Conclusions: These results provide further evidence for the combined involvement of both Alzheimer type pathology and vascular pathology in the earliest stages of cognitive decline and suggest an additive effect of WMH and MTA.

Background: Cerebral small vessel disease is a common cause of cognitive impairment and vascular dementia. The cognitive deficit differs from that in Alzheimer’s disease, with greater executive/attentional dysfunction and relatively intact episodic memory. Objective: To develop brief assessment tools that are better adapted to the neuropsychological profile of cerebral small vessel disease. Methods: 32 subjects with ischaemic leukoaraiosis (history of lacunar stroke and leukoaraiosis on MRI), aged 50 to 84 years, and 17 age and education matched controls had a brief executive assessment, which took 20 minutes to administer, and a wide range of additional tests. The ability of the brief executive assessment to discriminate between groups—both individually and in combination—was evaluated and compared with that of the whole battery. Results: The brief executive assessment provided good sensitivity and specificity for identifying subjects with ischaemic leukoaraiosis (sensitivity 88%, specificity 88%, using the optimal combination of scores). The best individual tests were trail making and digit symbol, which were both far more sensitive than the mini-mental state examination (MMSE). The ability to discriminate between groups was maintained in subjects with MMSE >27 and across the whole age range. The brief executive assessment performed well compared with the whole battery, with additional tests accounting for only a further 12% of between-group variance. Conclusions: The brief executive assessment was sensitive to deficits found in ischaemic leukoaraiosis and discriminated them from the cognitive effects of healthy aging. The assessment has potential for bedside use and as a cognitive end point for clinical trials.

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.

Objective: To study the safety and efficacy of a cholinesterase inhibitor, donepezil hydrochloride, for the treatment of dementia in Parkinson's disease (PD). Methods: This was a randomised double blind, placebo controlled, crossover study in 22 subjects with PD and dementia. Participants were randomised to receive either donepezil followed by identical placebo, or placebo followed by donepezil. Donepezil was administered at 5–10 mg/day. Treatment periods were 10 weeks with a washout period of 6 weeks between the two periods. The primary outcome measure was the Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAScog). Results: Donepezil was well tolerated and most adverse events were mild. There was no worsening of PD symptoms as measured by the total or motor sections of the Unified Parkinson's Disease Rating Scale. There was a 1.9 point trend toward better scores on the ADAScog on treatment compared with placebo that was not statistically significant. The secondary cognitive measures showed a statistically significant 2 point benefit on the Mini Mental Status Examination and no change on the Mattis Dementia Rating Scale (MDRS). The Clinical Global Impression of Change (CGI) showed a significant 0.37 point improvement on donepezil. No improvement was observed on the MDRS or the Brief Psychiatric Rating Scale. Carryover between treatment periods was observed but was not statistically significant. Conclusions: Donepezil was well tolerated and did not worsen PD. There may be a modest benefit on aspects of cognitive function. The possible clinical benefit measured by CGI was reflected in only one of the cognitive scales used in this study.

To determine in vivo cortical acetylcholinesterase (AChE) activity and cognitive effects in subjects with mild Alzheimer's disease (AD, n = 14) prior to and after 12 weeks of donepezil therapy.Cognitive and N-[(11)C]methyl-piperidin-4-yl propionate ([(11)C]PMP) AChE positron emission tomography (PET) assessments before and after donepezil therapy.Analysis of the PET data revealed mean (temporal, parietal, and frontal) cortical donepezil induced AChE inhibition of 19.1% (SD 9.4%) (t = -7.9; p0.0001). Enzyme inhibition was most robust in the anterior cingulate cortex (24.2% (6.9%), t = -14.1; p0.0001). Donepezil induced cortical inhibition of AChE activity correlated with changes in the Stroop Color Word interference scores (R(2) = 0.59, p0.01), but not with primary memory test scores. Analysis of the Stroop test data indicated that subjects with AChE inhibition greater than the median value (22.2%) had improved scores on the Stroop Color Word Test compared with subjects with less inhibition who had stable to worsening scores (t = -2.7; p0.05).Donepezil induced inhibition of cortical AChE enzyme activity is modest in patients with mild AD. The degree of cortical enzyme inhibition correlates with changes in executive and attentional functions.

Aims: To investigate the dynamic time course of transient global amnesia (TGA)—that is, the process of recovery and the interindividual variability—by testing four patients during the day of TGA itself (on three occasions) and at follow up (on two occasions). Methods: A specially designed protocol focusing on semantic (both conceptual and autobiographical knowledge) and episodic (both anterograde and retrograde components) memory. Results: Every patient showed marked impairment of both anterograde and retrograde episodic memory during the acute phase, with a relative preservation of personal and conceptual semantic knowledge. During the following phase, the authors observed similarities and differences among the patients' patterns of recovery. In general, retrograde amnesia recovered before the anterograde amnesia and anterograde episodic memory was recovered gradually in every case. In contrast, shrinkage of retrograde amnesia was more heterogeneous. In two of the patients, this shrinkage followed a chronological gradient and the most remote events were recovered first. In the two other patients, it depended more on the strength of the trace, and there was no temporal gradient. For the latter, an executive deficit could account for difficulties in accessing both conceptual knowledge and autobiographical memories. Conclusions: This profile of recovery suggests a "neocortical to medial temporal" process in every case, and the possibility of an additional frontal dysfunction in some cases. Hence, the acute phase seems to be characterised by a common episodic impairment. This variability between subjects appears in the recovery phase with two different patterns of impairment.

Background: Anosognosia is a common manifestation of Alzheimer's disease. There is an association between impaired awareness and frontal-executive cognitive deficits. Anosognosia is also correlated with decreased metabolism in the right hemisphere, particularly in frontal lobe regions. Objective: To investigate pathological correlates of anosognosia in Alzheimer's disease. Design: 41 subjects followed longitudinally in the University of Pittsburgh memory disorders clinic and with necropsy verified Alzheimer's disease were divided into two groups, based on previous clinical assessment: +Aware (n = 23) and –Aware (n = 18). A subset analysis matching subjects for dementia severity using mini-mental state examination scores was also carried out (13 +Aware; 13 –Aware). Histopathological data from necropsy brain tissue consisted of senile plaque (SP) and neurofibrillary tangle (NFT) counts (regional density) from four different brain regions in the right and left hemispheres: superior and middle frontal gyri (SMF), superior temporal isocortex (ST), the prosubiculum of the hippocampus (PRO), and the entorhinal cortex (EC). Results: SP density was greater in the right PRO region of –Aware subjects (F = 6.54, p = 0.015) than +Aware subjects. Significant differences between SP or NFT density were not observed in any other regions. In the subset analysis matching for dementia severity, SP density was again greater in the right PRO region of –Aware subjects than in the other regions (F = 12.72, p = 0.002). Conclusions: Increased SP density in the right PRO region suggests that selective pathological involvement of this area contributes to awareness deficits in Alzheimer's disease. The putative role of the PRO in self appraisal may reflect its interconnections with other medial temporal and prefrontal regions.

Objectives: To document and illustrate qualitative features of fluctuating cognition as described by care givers of patients with probable dementia with Lewy bodies (DLB) and Alzheimer’s disease (AD). To determine whether the quality of the fluctuations differs between DLB and AD. To examine the clinical utility of two recently developed rating scales. Methods: Care givers of 13 patients with early probable DLB and 12 patients with early probable AD were interviewed using the Clinician Assessment of Fluctuation and the One Day Fluctuation Assessment Scale, both developed recently. Descriptions of fluctuating cognition were recorded verbatim, analysed, and rated. Results: Descriptions of fluctuating cognition in DLB had a spontaneous, periodic, transient quality, which appeared to reflect an interruption in the ongoing flow of awareness or attention that impacted on functional abilities. Descriptions of fluctuations in AD frequently highlighted episodes of memory failure, or a more enduring state shift in the form of “good” and “bad” days, typically occurring in response to the cognitive demands of the immediate environment. These qualitative differences could be detected reliably by independent raters, but were not always captured in standard severity scores. Conclusion: Fluctuations occuring in DLB have particular characteristics that are distinguishable from fluctuations occurring in AD. Interpretation and application of the fluctuation criterion continues to limit the diagnostic sensitivity of the consensus criteria for DLB. Findings suggest that explicit documentation and a wider appreciation of these distinctions could improve the reliability with which less experienced clinicians identify this core diagnostic feature in the clinical setting.

Objectives:To characterise the neuropathological phenotypes of two affected individuals from a family with an unusual clinical phenotype resembling motor neurone disease and dementia. Methods:Histological sections of cerebral cortex, basal ganglia, brain stem, cerebellum, and spinal cord were stained with haematoxylin-eosin, luxol fast blue, silver stains, anti-tau, anti-ubiquitin, anti-α-synuclein, and anti-neurofilament. Results:Numerous ubiquitin positive, tau and α-synuclein negative intraneuronal inclusions were present in the cerebral cortex (particularly within the dentate gyrus), cerebellar cortex, brain stem, and spinal cord. The cerebellar ubiquitinated inclusions were located in the proximal dendrite of the Purkinje cells. Loss of Purkinje cells and occasional silver and neurofilament positive axonal swellings (torpedoes) were also seen within the cerebellar cortex. The main difference between the two cases was the severity of the spinal cord involvement: no significant pathology was present within one, but obvious motor neurone disease within the other. Conclusions:The clinical and neuropathological findings in this family are best described as an example of familial motor neurone disease with dementia. Intraneuronal ubiquitin inclusions together with agyrophilic, neurofilament positive torpedoes were present within the cerebellar cortex, both previously unrecognised findings in this group of diseases.

Objective: To document the prevalence and pattern of stereotypic behaviour in patients with Alzheimer's dementia and frontal and temporal variants of frontotemporal dementia. Secondly, to examine the relationship between stereotypic and other neuropsychiatric behaviours. Methods: Patients with the following were studied; Alzheimer's disease (n=28), frontal variant frontotemporal dementia (fvFTD, n=18), and semantic dementia—the temporal lobe variant of FTD (n=13). All patients were assessed using the Neuropsychiatric Inventory (NPI), the Mini-Mental State Examination, Addenbrooke's Cognitive Examination, and the Clinical Dementia Rating scale. Patients were also rated on the newly devised Stereotypic and Ritualistic Behaviour (SRB) subscale, which was designed as an addendum to the NPI. Results: There was no significant difference across diagnostic groups in terms of age, sex, or severity of cognitive deficits. The overall NPI was significantly higher in patients with fvFTD compared with the other two groups, but fvFTD and semantic dementia showed a similar, and significantly increased, prevalence of stereotypic behaviours on the SRB subscale. Within the FTD group as a whole these behaviours were more likely to be complex, whereas in Alzheimer's disease, when present, such behaviours tended to be more simple stereotypies or stimulus bound repetitive behaviours. Stereotypic behaviours were not correlated with either disease severity or the extent of cognitive impairment in the fvFTD group, but were in the other two diagnostic groups. Conclusion: Complex stereotypic behaviours are a core feature of the dementing syndrome in FTD and may reflect early and specific deficits in orbitofrontal circuitry and basal ganglia involvement.

Objectives: To investigate the prevalence of the frontal lobe syndrome (FLS) and the frontal variant of frontotemporal dementia (fvFTD) in a population based sample of 85 year olds. Methods: A representative sample of 85 year olds (n = 451) in Gothenburg, Sweden was examined with a neuropsychiatric examination and a key informant interview performed by an experienced psychiatrist. A subsample underwent computed tomography (CT) of the head. The Lund-Manchester research criteria were used as a basis for a symptom algorithm to identify individuals with FLS and fvFTD. These were diagnosed blindly to the diagnosis of dementia according to DSM-III-R. Results: A total of 86 individuals (19%) fulfilled the criteria for FLS, and 14 of them fulfilled criteria for fvFTD. There were no differences between men and women. Among those with FLS, 75 (87%) fulfilled DSM-III-R criteria for other types of dementia, mainly Alzheimer's disease and vascular dementia. Among the 14 fvFTD cases, only five were demented according to DSM-III-R. Moderate to severe frontal atrophy was found in 93% of those with FLS (and in all cases with fvFTD), but also in 49% of those without FLS. FLS was found in 35% of those with moderate to severe frontal atrophy, and in 3% of those without these changes. Conclusions: The prevalence of fvFTD was 3% in 85 year olds, which is higher than previously expected in this age group. Only a minority of those with fvFTD were detected by the DSM-III-R criteria for dementia. FLS was even more common, especially in those diagnosed with a dementia disorder.

Background: Although neuropsychiatric complications are well recognised, the presentation of multiple sclerosis with cognitive or neuropsychiatric symptoms has generally been considered a rare occurrence and to reflect subcortical pathology. Objectives: To document the clinical, neuropsychological, and radiological features of six cases of cognitive presentation of multiple sclerosis, to review the relevant literature, and to propose a possible cortical basis for this clinical presentation. Subjects: Six patients (five women; age range 38 to 60 years) presented to the memory and cognitive disorders clinic in Cambridge with an initially undiagnosed cognitive/neuropsychiatric syndrome. All underwent neuropsychological evaluation, brain imaging, and ancillary investigations to establish a diagnosis of multiple sclerosis. Results: The six cases all had a progressive dementia syndrome with prominent amnesia, often accompanied by classic cortical features including dysphasia, dysgraphia, or dyslexia. Mood disturbance was ubiquitous and in three patients there was a long history of preceding severe depression. All six developed characteristic physical signs on follow up, with marked disabilities. A review of 17 previously reported cases highlighted the prominence of memory impairment and depression in the early stages. Conclusions: On clinical, pathological, and radiological grounds, the neuropsychiatric presentation of multiple sclerosis may represent a clinicopathological entity of "cortical multiple sclerosis." Failure to recognise this will delay diagnosis and may expose patients to potentially dangerous and invasive investigation. Because the neuropsychiatric features of cortical multiple sclerosis are a major cause of handicap, their early recognition may be particularly important in view of emerging treatments.

Objective: To estimate the prevalence of dementia with Lewy bodies (DLB) according to the consensus criteria in a general population aged 75 years or older. Methods: The “Kuopio 75+ study” is a population based health survey focused on the clinical epidemiology of dementia and functional capacity among elderly subjects aged 75 years or older. On 1 January 1998, a random sample of 700 subjects was drawn from a total population born before 1 January 1923, living in the city of Kuopio, northeast Finland (n = 4518). The study subjects underwent a structured interview and clinical examination. Results: 601 elderly subjects (86% of the random sample) were examined. A dementia disorder was diagnosed in 137—a prevalence of 22.8% (95% confidence interval 19.4% to 26.2%). The prevalence of DLB was 5.0% (3.2% to 6.7%), comprising 22% of all demented subjects. Probable DLB was diagnosed in 20 subjects (3.3% (1.9% to 4.8%)), and possible DLB in 10 (1.7% (0.6% to 2.7%)). The prevalence of Alzheimer’s disease was 10.6% (47% of all demented subjects), of vascular dementia, 5.3% (23%), and of other types of dementing disorders, 1.8% (8%). Conclusions: In a general population aged 75 years and older, the prevalence of a disorder fulfilling the diagnostic criteria of DLB is half that of Alzheimer’s disease and the same as for vascular dementia.

Background: Verbal memory impairment, one of the earliest signs of Alzheimer’s disease (AD), may help identify people with cognitive impairment, insufficient for a diagnosis of dementia (questionable dementia: QD), at risk of developing AD. Other cognitive parameters have been found that may indicate which people with QD will go on to develop dementia. Nevertheless, some researchers have reported only partial success in differentiating between mild AD and age related cognitive impairment. Objectives: To discover if there are early, pre-clinical cognitive markers that could help identify patients attending our memory clinic who were at risk of developing dementia. Methods: Multidisciplinary assessment of a consecutive sample of 195 patients with QD seen in a National Health Service hospital outpatient clinic; 135 seen for a mean follow up of 24.5 months. Results: Conversion rate to dementia was 27.4% (37 of 135). A diagnosis of probable or possible AD was made in 15.6% (21 of 135) of cases. Despite statistically significant differences in some cognitive tasks between those who did and those who did not go on to dement, Cox regression analyses failed to improve prediction rates markedly above base rates and were unstable. Conclusion: A large number of studies claim good prediction of conversion to dementia using cognitive test scores. Although this study produced similarly good sensitivity and specificity values, proper consideration of the statistical analyses and their clinical significance suggested that these prediction methods are currently too imprecise for clinical use. Use of cognitive indicators combined with neuroradiological, neuropathological, and genetic factors for predicting conversion to dementia might prove more reliable but may be beyond the scope of many geriatric services.

Objectives: To accurately establish the incidence of falls in Parkinson9s disease (PD) and to investigate predictive risk factors for fallers from baseline data. Methods: 109 subjects with idiopathic PD diagnosed according to the brain bank criteria underwent a multidisciplinary baseline assessment comprising demographic and historical data, disease specific rating scales, physiotherapy assessment, tests of visual, cardiovascular and autonomic function, and bone densitometry. Patients were then prospectively followed up for one year using weekly prepaid postcards along with telephone follow up. Results: Falls occurred in 68.3% of the subjects. Previous falls, disease duration, dementia, and loss of arm swing were independent predictors of falling. There were also significant associations between disease severity, balance impairment, depression, and falling. Conclusions: Falls are a common problem in PD and some of the major risk factors are potentially modifiable. There is a need for future studies to look at interventions to prevent falls in PD.

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.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.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.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.