Longitudinal study of the early neuropsychological and cerebral metabolic changes in dementia of the Alzheimer type

Abstract

To examine the progression of neuropsychologic and metabolic changes in the early stages of dementia of the Alzheimer type (DAT), we studied 11 mildly demented patients longitudinally. Three aspects of neuropsychological function were measured: memory, attention to complex sets and abstract reasoning, and lateralized functions, i.e., language and visuoconstruction. Regional cerebral metabolic rates for glucose were measured in frontal, parietal, and temporal association cortices. Our results show that, in general, memory deficits are the first neuropsychological impairments to occur in DAT, followed by problems with attention to complex cognitive sets and abstract reasoning, which are followed in turn by deficits in language and visuospatial abilities. In addition, neocortical metabolic abnormalities usually precede impairment of neocortically mediated attention and abstract reasoning by 8 to 16 months, and precede impairment of neocortically mediated language and visuospatial function by 12 to 37 months. These findings suggest that the first nonmnestic neuropsychological consequence of neocortical physiological dysfunction in DAT is a loss of attentional capacity. Since neocortical metabolic changes generally precede the appearance of neocortically mediated neuropsychological dysfunction, physiologic dysfunction may exist for some time before cognition is affected.     

Longitudinal study of the early neuropsychological and cerebral metabolic changes in dementia of the Alzheimer type

To examine the progression of neuropsychologic and metabolic changes in the early stages of dementia of the Alzheimer type (DAT), we studied 11 midly demented patients longitudinally. Three aspects of neuropsychological function were measured: memory, attention to complex sets and abstract reasoning, and lateralized functions, i.e., language and visuoconstruction. Regional cerebral metabolic rates for glucose were measured in frontal, parietal, and temporal association cortices. Our results show that, in general, memory deficits are the first neuropsychological impairments to occur in DAT, followed by problems with attention to complex cognitive sets and abstract reasoning, which are followed in turn by deficits in language and visuospatial abilities. In addition, neocortical metabolic abnormalities usually precede impairment of neocortically mediated attention and abstract reasoning by 8 to 16 months, and precede impairment of neocortically mediated language and visuospatial function by 12 to 37 months. These findings suggest that the first nonmnestic neuropsychological consequence of neocortical physiological dysfunction in DAT is a loss of attentional capacity. Since neocortical metabolic changes generally precede the appearance of neocortically mediated neuropsychological dysfunction, physiologic dysfunction may exist for some time before cognition is affected.     

Cognitive deficits of mild dementia:A comparison between dementia of the Alzheimer's type and vascular dementia

Abstract This study was designed to examine the profiles of cognitive deficits in 11 mildly demented patients with dementia of Alzheimer's type (DAT), five with vascular dementia with multiple subcortical lacunar infarcts (VDS), and seven with vascular dementia with extensive white matter lesions (VDW) in comparison with 23 aged individuals without dementia. Memory, attention, abstract thinking, and visuospatial function were assessed using the Japanese translation of the Wechsler Memory Scale-Revised (WMS-R) and the Japanese version of the Wechsler Adult Intelligence Scale-Revised (WAIS-R). Compared with normal aged individuals, three dementia groups were significantly impaired in the memory and abstract thinking. However, the performances on several tests on attention (i.e. Mental Control and Visual Memory Span Backward from WMS-R) and visuospatial function (i.e. Object Assembly from WAIS-R) differed significantly between the DAT and VDS groups, with VDS being the worst in terms of performance than was DAT. This study suggests that, in the mildly demented stage, the patients with DAT have few problems in the attention and visuospatial function, but those with VDS have impairments in these cognitive abilities.     

Sparing of attentional relative to mnemonic function in a subgroup of patients with dementia of the Alzheimer type

Patients with dementia of the Alzheimer type (DAT) received two tests of visual selective attention, together with tests of spatial and visual recognition memory and visuospatial conditional learning previously used to show deficits early in the course of DAT. One set of attentional tests compared visual discrimination learning along intra- and extra-dimensional shifts, using a "total change" design. In the 12 DAT patients capable of attempting the extra-dimensional shift (subgroup 1), performance was equivalent to that of controls. This subgroup was also unimpaired at simple and compound discrimination learning and reversal and an intra-dimensional shift. They were as accurate as controls on a visual search task requiring matching of stimuli on two dimensions with variable numbers of alternatives, but were significantly impaired in the tests of recognition memory and learning. By contrast, the other 13 patients showed marked impairments in the attentional tasks. This subgroup was also significantly worse than subgroup 1 in performance on the visual recognition and conditional learning tasks, and showed greater severity on most of the clinical ratings of dementia. The sparing of attentional shifting in patients early in the course of DAT is contrasted with the impairments previously described in patients with Parkinson's disease with only mild or absent memory loss. The implications of this double dissociation of deficits for understanding the neural bases of the cognitive deficits in these two neurodegenerative diseases are discussed and their significance for the staging of DAT is considered.     

Stability of metabolic and neuropsychological asymmetries in dementia of the Alzheimer type

We examined right/left asymmetries in cerebral glucose utilization and neuropsychological performance in 16 patients with dementia of the Alzheimer type (DAT) who were studied twice over a mean interval of 15 months. Neuropsychological asymmetry was expressed as the difference between performance on a visuoconstructive task and a language task. Test/retest comparisons showed significant declines on the neuropsychological measures, but no significant changes in the neuropsychological and metabolic asymmetry indices. At both evaluations, significant correlations were found between neuropsychological asymmetry and metabolic asymmetry in frontal and parietal cortex. Individual patterns of metabolic and neuropsychological asymmetry in these patients with DAT seem to be stable.     

Neocortical metabolic abnormalities precede nonmemory cognitive defects in early Alzheimer's-type dementia

Neuropsychological function and resting regional neocortical glucose metabolism, as measured by positron-emission tomography, were studied in 22 patients with mild and moderate Alzheimer's-type dementia. Metabolic reductions in the parietal association cortex and increased left-right metabolic asymmetry were observed in patients with mild and moderate degrees of dementia. Five patients with mild dementia had no impairment of neocortically mediated neuropsychological function, yet they demonstrated these same neocortical metabolic abnormalities. Asymmetry of neocortically mediated, neuropsychological functions correlated with metabolic asymmetries in patients with moderate but not mild dementia. These results suggest that physiological dysfunction in the that physiological dysfunction in the association neocortex is evident in early Alzheimer's-type dementia before the neuropsychological consequences of that dysfunction are demonstrable.     

Topographical analysis of glucose metabolism, as measured with positron emission tomography, in dementia of the Alzheimer type: use of linear histograms

A linear histogram method was employed to analyze brain images of glucose uptake obtained by positron emission tomography in patients with dementia of the Alzheimer type and in control subjects. A line was drawn by computer which traversed the image of a brain slice taken at 70 mm above and parallel to the inferior orbitomeatal line, and rCMRglc was plotted as a function of distance along this line in 3 brain areas: frontal, sensorimotor and parietal. Peak rCMRglc values were significantly decreased in moderately-to-severely demented patients relative to healthy age-matched controls, but not in mildly demented patients. Furthermore, both the mildly and the more severely demented patients differed from controls in having reduced ratios of parietal association to sensorimotor peak rCMRglc. The variances of right-left metabolic asymmetries did not differ significantly between Alzheimer patients and controls. Severity of dementia, as evaluated by scores on the Mini-Mental State Examination, correlated with ratios of peak rCMRglc in frontal and parietal cortex to that in sensorimotor cortex. These results indicate that measures of focal peak rCMRglc do not discriminate between mildly demented patients and controls, whereas focal ratios of rCMRglc, where the denominator corresponds to rCMRglc from a relatively spared region, provide useful measures of metabolic dysfunction in the early stages of Alzheimer's disease.     

Neuropsychological assessment in the diagnosis and differential diagnosis of fronto-temporal dementia

Clinical diagnosis of fronto-temporal dementia (FTD) and its rare variants (semantic dementia and primary progressive aphasia) represents a special challenge bearing in mind its difficulties and is important due to therapeutic differences with the most common Alzheimer's dementia. Of note, cholinesterase inhibitors commonly prescribed in Alzheimer's disease are not effective in FTD and a novel drug, memantine, has not been evaluated as yet. Neuropsychological evaluation is an important add-on to neurological, psychiatric and neuroimaging assessments in the clinical diagnosis of FTD. In this paper, we have described characteristics of neuropsychological deficits observed in FTD (such as attention, language, visuospatial and memory impairments) as well as tools used (tests) in clinical practice. Special attention is paid to the utility of neuropsychological examination in the differential diagnosis of FTD versus Alzheimer's disease, vascular dementia and other, less common forms of dementia.     

Patterns of neuropsychological impairment in mild dementia: a comparison between Alzheimer's disease and multi-infarct dementia

The objective was to investigate the clinical and psychometric differences between patients with dementia of Alzheimer type (DAT) and patients with multi-infarct dementia (MID), matched for age, sex, education, and severity. Sixteen patients with DAT, 16 patients with MID, and 30 healthy individuals, were drawn from a longitudinal study on aging and dementia. Subjects with medical or previous mental disorders were excluded. DAT and controls with focal brain abnormalities on magnetic resonance imaging (MRI) were excluded. Diagnosis of dementia was carried out according to DSM-III-R criteria. Dementia severity was staged using the Clinical Dementia Rating (CDR) scale, and only patients with a score of 0.5-1 on CDR were studied. The main outcome measures were quantitative clinical scales of the assessment of global mental status, depression and anxiety, as well as a wide battery of neuropsychological tests for the evaluation of executive/conceptual functions and memory, as well as attention verbal ability, and visuospatial skill functions. The performance of demented patients compared to normal controls was affected on all measurements except for depression and anxiety. DAT patients showed compared to MID patients a greater extent of impairment on tasks assessing verbal comprehension and memory while MID patients were more significantly impaired on measures of frontal lobe functioning. Clinically matched DAT and MID patients show a differential pattern of neuropsychological impairment when studied in an early stage of dementia and with a mild degree of severity. Such patterns might be of value for the development of clinical diagnostic criteria.     

Distinctive cognitive profiles in Alzheimer's disease and subcortical vascular dementia

BACKGROUND: There are inconsistencies in published reports regarding the profile of cognitive impairments in vascular dementia, and its differentiation from Alzheimer's disease. OBJECTIVES: To identify the overall profile of cognitive impairment in subcortical vascular dementia as compared with Alzheimer's disease; and the tests which best discriminate between these groups. METHODS: 57 subjects participated: 19 with subcortical vascular dementia, 19 with Alzheimer's disease, and 19 controls. The dementia groups were matched for age, education, and general levels of cognitive and everyday functioning. Subcortical vascular dementia was defined by clinical features (prominent vascular risk factors plus a previous history of transient ischaemic events or focal neurological signs) and substantial white matter pathology on magnetic resonance imaging. All subjects were given a battery of 33 tests assessing episodic and semantic memory, executive/attentional functioning, and visuospatial and perceptual skills. RESULTS: Despite a minimal degree of overall dementia, both patient groups had impairments in all cognitive domains. The Alzheimer patients were more impaired than those with vascular dementia on episodic memory, while the patients with vascular dementia were more impaired on semantic memory, executive/attentional functioning, and visuospatial and perceptual skills. Logistic regression analyses showed that the two groups could be discriminated with 89% accuracy on the basis of two tests, the WAIS logical memory--delayed recall test and a silhouette naming test. CONCLUSIONS: Subcortical vascular dementia and Alzheimer's disease produce distinctive profiles of cognitive impairment which can act as an adjunct to diagnosis. Many of the neuropsychological deficits thought to characterise Alzheimer's disease are also found in subcortical vascular dementia.     

Mild cognitive impairment in the elderly: predictors of dementia

We conducted full diagnostic evaluations, including a comprehensive cognitive assessment battery, of a group of 32 elderly subjects with a clinically identified mild cognitive impairment and a group of 32 age-matched and education-matched normal subjects. The mildly impaired subjects performed significantly more poorly than the controls on tests of recent memory, remote memory, language function, concept formation, and visuospatial praxis. Follow-up evaluations of cognitive status 2 years later revealed clinically detectable cognitive decline relative baseline in 23 (72%) of the mildly impaired subjects. Several of the objective psychological tests accurately discriminated at baseline between the decliners and nondecliners in the mildly impaired group. Among the 20 mildly impaired subjects with no complicating conditions, 16 exhibited cognitive deterioration between baseline and follow-up. These results suggest that most elderly subjects with mild cognitive deficits, as determined by clinical evaluation and objective psychological testing, will manifest the progressive mental deterioration characteristic of dementia and that psychometric predictors can be used to distinguish between benign and more significant underlying disorders in mildly impaired elderly subjects.     

Executive dysfunction in spinocerebellar ataxia type 1.

Fourteen patients with spinocerebellar ataxia 1 (SCA1) and 11 controls with similar mean age and IQ estimates were submitted to a neuropsychological test battery comprising tests for IQ, attention, verbal and visuospatial memory as well as executive functions. Neuropsychological assessment yielded verbal memory and executive dysfunction while tests of visuospatial memory and attention were not significantly impaired in SCA1 as compared to controls. Test performance was neither related to the repeat length, the age of onset nor the disease duration. The profile of cognitive impairment in SCA1 with prominent executive dysfunction corresponds to the concept of "frontal-subcortical" dementia that is likely to be contingent upon disruption of a cerebrocerebellar circuitry that consists of afferent and efferent connections between the prefrontal cortex and the cerebellum.     

Neuropsychological evaluation of adults with Down's syndrome: patterns of selective impairment in non-demented old adults

A batiery of neuropsychological tests, developed to study patterns of age-related differences in adults with Down's syndrume (DS), was administered to 10 DS adults over age 35 and 19 younger DS adults. Although all adults with DS are reported to develop the neuropathoiogical changes of Alzheimer's disease by the fourth decade of life, only four of the 10 old DS adults were judged to have dementia based on clinical criteria. Demented old DS adults had global neuropsychological deficits, as indicated by significant differences on all functions tested except some simple language functions. In contrast, non-demented old adults had a selective pattern of neuropsychological reductions relative to young adults. Ability to form new long-term memories and visuospatial construction were consistently diminished, whereas immediate memory span and language were not. The global mental decline observed in demented adults suggests a stage of disease progression that corresponds to severe dementia in pre- morbidly normal adults with dementia of the Alzheimer type (DAT). The prominent long-term memory impairment with selective reductions of nonmemory functions in non-demented adults suggests a correspondence to early and intermediate DAT.     

Clinical and imaging characteristics of dementia in multiple system atrophy

BackgroundRecent reports show that dementia occurs in 5–26% of multiple system atrophy (MSA) patients. However, the structural or pathological correlates of dementia in MSA are unclear yet.MethodsOf 152 patients with MSA, 59 fulfilled the criteria of probable MSA and 9 (15%) had dementia. Six of those patients and 9 without dementia, in addition to 10 controls, were included. All subjects underwent clinical evaluation including UMSARS, neuropsychological examinations, 3T-MRI, and Pittsburgh Compound B (PIB) PET imaging. The cortical thickness was assessed using surface-based morphometry.ResultsAge and disease duration were similar between MSA with dementia and without dementia, while motor disability was more severe in MSA with dementia. In neuropsychological tests, attention, visuospatial function, and language function were impaired in MSA with dementia. Mean PIB binding was similar among the three groups. Cortical thickness was reduced in precuneus/cuneus, uncus, and posterior cingulate in MSA with dementia compared to the controls, and in parahippocampal and lingual cortices compared to MSA without dementia.ConclusionsDementia was found in 15% of the probable MSA patients, which was similar to those reported in previous studies. It appears that amyloid pathology has limited role in dementia in MSA, although some patients had increased cortical amyloid burden. Cortical thinning in MSA-D was observed in areas where cortical thinning was reported in Alzheimer disease or Parkinson disease dementia, but its pathological relevance is unclear. The neuropathological processes leading to the development of dementia in MSA appears to be multifactorial and heterogenous.     

Differences between Pick disease and Alzheimer disease in clinical appearance and rate of cognitive decline

OBJECTIVES: To define the cognitive characteristics of Pick disease (PcD), and to determine which features distinguish PcD from Alzheimer disease (AD), in a cross-sectional and longitudinal study. METHODS: The participants were 44 patients with PcD (10 pathologically verified), 121 patients with AD (14 pathologically verified), and 60 normal control subjects. We obtained information regarding the initial symptom of dementia from each patient's caregiver, estimated global dementia severity by the Blessed Dementia Scale and the Activities of Daily Living Scale, and assessed specific cognitive domains by administering 10 tests of memory, language, visuospatial, and reasoning abilities and selective attention. RESULTS: Among initial symptoms reported by caregivers, personality change and language impairment were significantly more common in PcD than AD; deficits in memory were common in both groups but more prevalent in AD (P<.001). At initial cognitive testing, the scores of patients with PcD were inferior to those of normal controls on all tests, except on a measure of visuospatial function; the scores of patients with AD were inferior to those of controls on all tests. Patients with PcD were superior to patients with AD on measures of explicit memory (P<.001) and visuospatial function (P = .001) but had greater impairments on the Activities of Daily Living Scale (P<.05). During the course of illness, patients with PcD declined significantly faster than those with AD on language tests and on global measures of dementia severity (P<.05), whereas measures of explicit memory and visuospatial and reasoning abilities worsened equally in both patient groups. CONCLUSIONS: There is a characteristic cognitive profile and course of dementia in PcD. Nonetheless, cognitive test performance does not clearly distinguish PcD from AD.     

Evidence for impaired sentence comprehension in early Alzheimer's disease.

We investigated sentence comprehension in 46 patients with probable minimal (very mild), mild, or moderate dementia of the Alzheimer type (DAT), comparing their performance on the Test for the Reception of Grammar (TROG), with that of 20 age- and education-matched controls. Performance on the TROG was generally related to dementia severity, independent of lexicosemantic and working memory (digit span) impairments, but related to at least 1 measure of attention. Some patients in the minimal group showed sentence comprehension deficits while others in the moderate group did not, indicating that DAT may impair sentence comprehension at the very earliest stages of disease, but that its effects are heterogeneous. Patients were most impaired on sentences with 2 propositions and noncanonical word order, suggesting difficulties with both interpretative and postinterpretative stages of sentence processing. Further investigation is needed into the relationship between attentional processes, interpretative and postinterpretative stages of syntactic processing in DAT.     

Comparison of positron emission tomography, cognition, and brain volume in Alzheimer''s disease with and without severe abnormalities of white matter.

OBJECTIVES--To examine cerebral metabolism, cognitive performance, and brain volumes in healthy controls and two groups of patients with probable Alzheimer's disease, one group with severe abnormalities of white matter (DAT+) and the other group with none, or minimal abnormalities (DAT-). METHODS--Neuropsychological tests, CT, MRI, quantitative MRI, and PET studies were carried out to allow comparison between the DAT+ and DAT- groups and the healthy controls. RESULTS--Compared with the healthy controls, both demented groups had significantly reduced global and regional cerebral metabolism, significant brain atrophy, and significantly lower scores on neuropsychological testing. The DAT- patient group showed a pattern of parietal-temporal cerebral metabolic reductions and neuropsychological performance deficits typical of Alzheimer's disease. In addition, metabolism in the association neocortex (AD ratio) and measures of neuropsychological task performance were significantly correlated in the DAT- patient group. Comparison of DAT+ with DAT- patients showed a significantly higher ratio of parietal to whole brain glucose utilisation for the DAT+ group. Moreover, when comparing group z score differences from the healthy controls, the DAT+ group had, on average, smaller differences from controls in the frontal, parietal, and temporal regions than did the DAT- group. Discriminant analysis using metabolic ratios of the frontal, parietal, and temporal regions showed cerebral metabolic patterns to be significantly different among the DAT+, the DAT-, and the healthy controls. These differences were due primarily to relatively higher frontal, parietal, and temporal metabolic ratios in the DAT+ group which resulted in discriminant scores for the DAT+ group between the healthy controls and the DAT- group. Group mean scores on tests of neuropsychological performance were not significantly different between the DAT- and DAT+ patients. By contrast with the DAT- group, however, no significant correlations between the AD ratio and any neuropsychological task were seen in the DAT+ group. Multiple regression analysis showed significant between group differences in the relation between the AD ratio and neuropsychological scores on three tasks. The slopes of the relations between the AD ratio and memory scores (memory and freedom from distractability deviation quotient of the Wechsler adult intelligence scale (WMDQ)) also were significantly different for the two groups. CONCLUSIONS--Although multiple causes for abnormalities of white matter exist in patients with Alzheimer's disease, these data suggest that the presence of severe abnormalities of white matter indicate a second pathological process in the DAT+ patients. The DAT- patients showed the parietal-temporal metabolic deficits and correlations between association neocortical metabolism and neuropsychological task performance typical of patients with Alzheimer's disease. By contrast, the DAT+ group had a pattern of cerebral metabolism significantly different from healthy controls and DAT+ patients, as well as no significant correlations between metabolism in the association neocortex and neuropsychological performance. These differences probably reflect the superimposed pathology of the abnormalities of white matter which may exert their affect through disruption of long corticocortical pathways.     

Cognitive deficits in beta-thalassemia major

OBJECTIVES: To assess cognitive functioning in patients affected by beta-thalassemia major (beta-th) by using a neuropsychological battery, and to identify clinical correlates. MATERIAL AND METHODS: Forty-six beta-th patients and 46 controls similar for age, sex, and education participated in the study. All subjects performed a comprehensive neuropsychological battery including tests of abstract reasoning, attention, executive functions, language, constructional/visuospatial skills, and memory. RESULTS: Compared to controls beta-th patients, in particular those showing signs of hemosiderosis, were significantly impaired on all neuropsychological tests. There was no relationship between cognitive performances and signs of deferoxamine toxicity, deferoxamine dosage, and levels of hemoglobin and ferritin, while duration of transfusional therapy and time interval between onset of blood transfusions and onset of chelating treatment correlated with performances of tests assessing abstract reasoning, attention, constructional/visuospatial skills, memory and with the scores of the Mini Mental State Examination. CONCLUSION: Our findings suggest that beta-th is associated with neuropsychological impairment involving multiple cognitive domains and argue for a potential role of hemosiderosis on cognitive functioning.     

Semantic memory is impaired in both dementia with Lewy bodies and dementia of Alzheimer's type: a comparative neuropsychological study and literature review

OBJECTIVE: To test the hypothesis that semantic impairment is present in both patients with dementia with Lewy bodies (DLB) and those with dementia of Alzheimer's type (DAT). METHODS: A comprehensive battery of neuropsychological tasks designed to assess semantic memory, visuoperceptual function, verbal fluency, and recognition memory was given to groups of patients with DLB (n=10), DAT (n=10) matched pairwise for age and mini mental state examination (MMSE), and age matched normal controls (n=15). RESULTS: Both DLB and DAT groups exhibited impaired performance across the range of tasks designed to assess semantic memory. Whereas patients with DAT showed equivalent comprehension of written words and picture stimuli, patients with DLB demonstrated more severe semantic deficits for pictures than words. As in previous studies, patients with DLB but not those with DAT were found to have impaired visuoperceptual functioning. Letter and category fluency were equally reduced for the patients with DLB whereas performance on letter fluency was significantly better in the DAT group. Recognition memory for faces and words was impaired in both groups. CONCLUSIONS: Semantic impairment is not limited to patients with DAT. Patients with DLB exhibit particular problems when required to access meaning from pictures that is most likely to arise from a combination of semantic and visuoperceptual impairments.     

Attention and fluctuating attention in patients with dementia with Lewy bodies and Alzheimer disease

BACKGROUND: Attentional deficits are described in the consensus clinical criteria for the operationalized diagnosis of dementia with Lewy bodies (DLB) as characteristic of the condition. In addition, preliminary studies have indicated that both attentional impairments and fluctuation of attentional impairments are more marked in patients with DLB than in patients with Alzheimer disease (AD), although neuropsychological function has not previously been examined in a large prospective cohort with confirmed diagnostic accuracy against postmortem diagnosis. METHODS: A detailed evaluation of attention and fluctuating attention was undertaken in 155 patients with dementia (85 with DLB and 80 with AD) from a representative hospital dementia case register and 35 elderly controls using the Cognitive Drug Research Computerized Assessment System for Dementia Patients computerized neuropsychological battery. Operationalized clinical diagnosis was made using the consensus criteria for DLB and the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria for AD. High levels of sensitivity and specificity have been achieved for the first 50 cases undergoing postmortem examination. RESULTS: The groups were well matched for severity of cognitive impairments, but the AD patients were older (mean age, 80 vs 78 years) and more likely to be female (55% vs 40%). Patients with DLB were significantly more impaired than patients with AD on all measures of attention and fluctuating attention (for all comparisons, t > or = 2.5, P<.001), and patients from both dementia groups were significantly more impaired than elderly controls for all comparisons other than cognitive reaction time, which was significantly more impaired in DLB patients than controls but was comparable in controls and AD patients. There were, however, significant associations between the severity of cognitive impairment and the severity of both attentional deficits and fluctuations in attention. CONCLUSIONS: This large prospective study confirms that slowing of cognitive processing, attention, and fluctuations of attention are significantly more pronounced in DLB and AD patients, although fluctuating attention is common in patients with moderate-to-severe AD. Deficits of cognitive reaction time appear to be specific to DLB, except in severe dementia. A detailed evaluation of attentional performance could make an important contribution to differential diagnosis, although the results need to be interpreted within the context of the overall severity of cognitive deficits.