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C Ballard

Publications and source records attributed to C Ballard.

At least 19 recordsLinked to original sources
PubMed2003

A comprehensive study of gray matter loss in patients with Alzheimer's disease using optimized voxel-based morphometry.

Voxel-based morphometry (VBM) has already been applied to MRI scans of patients with Alzheimer's disease (AD). The results of these studies demonstrated atrophy of the hippocampus, temporal pole, and insula, but did not describe any global brain changes or atrophy of deep cerebral structures. We propose an optimized VBM method, which accounts for these shortcomings. Additional processing steps are incorporated in the method, to ensure that the whole spectrum of brain atrophy is visualized. A local group template was created to avoid registration bias, morphological opening was performed to eliminate cerebrospinal fluid voxel misclassifications, and volume preserving modulation was used to correct for local volume changes. Group differences were assessed and thresholded at P < 0.05 (corrected). Our results confirm earlier findings, but additionally we demonstrate global cortical atrophy with sparing of the sensorimotor cortex, occipital poles, and cerebellum. Moreover, we show atrophy of the caudate head nuclei and medial thalami. Our findings are in full agreement with the established neuropathological descriptions, offering a comprehensive view of atrophy patterns in AD.

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PubMed2002

Volumetric MRI study of the caudate nucleus in patients with dementia with Lewy bodies, Alzheimer's disease, and vascular dementia.

OBJECTIVES: To determine whether parkinsonian symptoms in dementia with Lewy bodies (DLB) are associated with greater atrophy of the caudate nucleus in comparison with patients with Alzheimer's disease (AD) and vascular dementia (VaD). METHODS: T1weighted MR scans were acquired in elderly patients with DLB, AD, VaD, and healthy controls. Normalised volumetric measurements of the caudate nucleus were obtained and parkinsonian symptoms rated using Hoehn and Yahr staging. RESULTS: There were no significant differences in the volume of the caudate nucleus between patients with dementia. However, the left caudate volume was significantly reduced in AD and DLB compared with controls. Parkinsonian symptoms did not correlate with caudate nucleus volume. CONCLUSIONS: Parkinsonian symptoms in DLB may be more closely coupled to neurochemical rather than structural changes in the caudate nucleus, and volumetric MRI analysis of caudate nucleus does not discriminate between patients with DLB, AD, and VaD.

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PubMed2001

Dementia with Lewy bodies and AD are not associated with occipital lobe atrophy on MRI.

Dementia with Lewy bodies (DLB) is associated with occipital changes in blood flow and metabolism, but structural changes in this region have not previously been assessed. The authors performed volumetric MRI measurement of the occipital lobe blind to the diagnosis in 23 subjects with DLB, 25 with AD, and 24 age-matched control subjects. There were no significant differences between groups in occipital lobe volume. The authors conclude gross structural changes in the occipital lobe do not occur in patients with mild to moderate DLB or AD.

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PubMed2001

Progressive brain atrophy on serial MRI in dementia with Lewy bodies, AD, and vascular dementia.

The authors determined rates of brain atrophy, as assessed by the boundary shift integral on serial MRI, in patients with dementia with Lewy Bodies (DLB, n = 10), AD (n = 9), vascular dementia (VaD, n = 9), and age-matched controls (n = 20). Mean % +/- SD atrophy rates per year were as follows: DLB, 1.4 +/- 1.1; AD, 2.0 +/- 0.9; VaD, 1.9 +/- 1.1; and controls, 0.5 +/- 0.7. Dementia subjects had higher rates than controls (p < 0.001), but there were no significant differences between the three dementia groups. The authors found accelerating atrophy with increasing severity of cognitive impairment, further emphasizing the need for early diagnosis and intervention in dementia.

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PubMed2001

Occipital hypoperfusion on SPECT in dementia with Lewy bodies but not AD.

OBJECTIVE: To compare regional cerebral blood flow (rCBF) changes using 99mTc-hexamethylpropyleneamine oxime (99mTc-HMPAO) SPECT in subjects with dementia with Lewy bodies (DLB) and AD and in normal age-matched control subjects; to examine the utility of SPECT changes in the differential diagnosis of AD and DLB. METHOD: Whole-brain SPECT scans were acquired using a single-headed rotating gamma camera (IGE CamStar XR/T) in elderly subjects with consensus criteria DLB (n = 23; mean age = 79.4 years), National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association AD (n = 50; 81.9 years), and normal control subjects (n = 20; 78.1 years) after injection with 500 MBq of 99mTc-HMPAO. Region-of-interest analysis was performed using a SPECT template registered in Talairach space, with rCBF normalized to cerebellum. RESULTS: Both DLB and AD subjects had significantly reduced rCBF in parietal and temporal regions compared with the control subjects. The AD group also showed a significant reduction in rCBF in the frontal and medial temporal regions and the DLB in the occipital areas compared with control subjects. AD and DLB groups differed only in occipital perfusion (p < 0.01). SPECT measures (occipital and medial temporal) correctly classified 69% of all subjects, with a 65% sensitivity and 87% specificity for DLB against AD and control subjects. CONCLUSION: Temporoparietal hypoperfusion on SPECT is common to both AD and DLB. Occipital hypoperfusion is more frequently seen in DLB. Although not diagnostically specific in individual cases, occipital hypoperfusion on SPECT should raise suspicion that DLB may be the cause of dementia, prompting careful search for other features of the disorder.

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PubMed2001

Cognitive impairment in depression is not associated with neuropathologic evidence of increased vascular or Alzheimer-type pathology.

BACKGROUND: Cognitive impairment is common in depression, but underlying mechanisms remain unknown. We examined whether increases in Alzheimer-type or vascular pathology are associated with cognitive impairments in elderly depressed subjects. METHODS: Eleven subjects who had died during a well-documented episode of DSM-IV major depression were included. Neuropathologic assessments, blind to group membership, included standardized assessment of neuritic plaques, neurofibrillary tangles, and Lewy Bodies in frontal, temporal, parietal, and occipital cortices. Braak staging of Alzheimer pathology was also performed. Cerebral microvascular disease was scored according to a previously validated scale, and a score for cerebral and systemic atheroma of large and medium sized arteries was obtained. RESULTS: No subject had Lewy bodies. Plaque and tangle counts for all subjects were well within published norms for age-matched control subjects. There were no significant differences in plaque or tangle counts between subjects who were cognitively impaired (n = 5) and those who were nonimpaired (n = 6) during their depressive illness. Similarly, neither total microvascular pathology nor deep frontal microvascular pathology differed between the two groups. CONCLUSIONS: Our results indicate that the liability for some patients to develop cognitive impairment during a depressive episode is not related to an increase in Alzheimer-type or vascular neuropathologic change. This indicates that other mechanisms must underlie both the cognitive impairment associated with depression and the observation that depression is a risk factor for dementia.

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PubMed2001

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.

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PubMed2001

Prevalence and pharmacological management of behavioural and psychological symptoms amongst dementia sufferers living in care environments.

BACKGROUND: Behavioural and psychological symptoms in dementia (BPSD) are a common reason for placement in long term care and are often associated with indiscriminate prescription of psychotropic medication. AIMS: To determine the prevalence of BPSD in care environments, their relationship with severity of dementia and the pattern of psychotropic medication. METHODS: Two hundred and thirty-one elderly residents (39% living in social care facilities and 61% in nursing home care) were assessed using a range of standardised psychiatric schedules. Additional information about the residents and medication was obtained from professional carers. RESULTS: Overall 90% of residents had dementia, 79% of whom had clinically significant BPSD with 58% receiving psychotropic medication. There was no difference in the prevalence of BPSD between social and nursing care. Depression was most common in people with mild dementia, whilst delusions arose most frequently in those with moderate dementia and aberrant motor behaviour had a high prevalence in people with severe dementia. CONCLUSION: BPSD are common in elderly people with dementia living in care environments. More rigorous guidelines are needed pertaining to the prescription and monitoring of medication and the need to disseminate skills regarding psychosocial management approaches to care staff.

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PubMed2001

The characterisation and impact of 'fluctuating' cognition in dementia with Lewy bodies and Alzheimer's disease.

BACKGROUND: Case reports and clinical observations suggest that fluctuating cognition (FC) is common in all the major dementias, particularly dementia with Lewy bodies (DLB) where it is one of three core clinical diagnostic features. The purpose of this study was to characterise FC and determine its impact upon activities of daily living. METHODS: Forty matched subjects (15 DLB, 15 AD, 10 elderly controls) were assessed using the activities of daily living scale (ADLD), the cognitive drug research (CDR) computerised neuropsychological test battery and a semi-standardised assessment of FC. The CDR battery was completed three times across a 1-week period, to evaluate variability in attention, visuospatial ability, working memory and delayed recall. RESULTS: There was a strong positive correlation between clinical FC scores and total mean ADLD. Measures of cognitive variability also demonstrated strong significant correlations with independent clinical severity ratings of FC across several cognitive domains. These associations were most powerful between attentional measures and clinical FC ratings. CONCLUSIONS: Although attention is the cognitive domain which fluctuates most markedly, other cognitive domains are also affected. FC also has a significant independent impact on activities of daily living.

Activities of Daily Living↗
PubMed2001

The progression of cognitive impairment in dementia with Lewy bodies, vascular dementia and Alzheimer's disease.

BACKGROUND: Little is known about the rate of progression or associations of cognitive impairment in dementia with Lewy bodies (DLB), or the associations of accelerated decline. METHOD: Dementia patients from a case register were evaluated at baseline and 1 year follow-up using the Cambridge Assessment for Mental Disorders in the Elderly, section B (CAMCOG) and the Mini-Mental State Examination (MMSE) to determine the rate of cognitive decline. Operationalized clinical diagnoses were applied (NINCDS ADRDA for Alzheimer's disease (AD), NINCDS AIRENS for vascular dementia (VaD) and consensus criteria for DLB). RESULTS: One hundred and ninety-three patients completed annual MMSE schedules (AD, 101; DLB, 64; VaD, 38), of whom 154 completed the CAMCOG. The magnitude of cognitive decline (MMSE, 4-5 points; CAMCOG, 12-14 points) was similar in each of the dementias. The strongest predictor of accelerated cognitive decline in DLB was the apolipoprotein E4 allele (17.5 vs 8.3 points decline on the CAMCOG). CONCLUSION: Over 1 year, DLB, VaD and AD patients had similar rates of cognitive decline overall. Apolipoprotein E4 may be an important predictor of more rapid decline in DLB.

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PubMed2001

A comparative study of psychiatric symptoms in dementia with Lewy bodies and Parkinson's disease with and without dementia.

OBJECTIVES: To compare the frequency and clinical correlates of neuropsychiatric symptoms in patients with Parkinson's disease (PD) with and without dementia and in those with dementia with Lewy bodies (DLB). METHODS: Neuropsychiatric symptoms during the month prior to assessment were assessed in clinically diagnosed PD patients with dementia (PDD; n = 48) and without dementia (PDND; n = 83) and in 98 DLB patients (33% autopsy confirmed) using standardized instruments. RESULTS: Delusions and hallucinations were significantly more common in DLB (57% and 76%) than PDD (29% and 54%) and PDND (7% and 14%) patients (p < 0.001). In all groups, auditory and visual hallucinations and paranoid and phantom boarder delusions were the most common psychotic symptoms. Frequency of major depression and less than major depression did not differ significantly between the three groups. Clinical correlates of hallucinations in PD were dementia (odds ratio (OR) = 3.9; 95% confidence interval (CI) 1.5-10.4) and Hoehn-Yahr stage 3 or more (OR 3.4; 95% CI 1.0-12.0), whereas no significant clinical correlates of hallucinations were found in DLB patients. CONCLUSIONS: Delusions and hallucinations occur with increasing frequency in PDND, PDD and DLB patients, but the presentation of these symptoms is similar. These findings support the hypothesis that psychiatric symptoms are associated with cortical Lewy bodies or cholinergic deficits in the two disorders.

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PubMed2001

Stroke and cognition.

Several studies confirm cognitive impairment and dementia to be increased after stroke in the elderly. Although not necessarily involving memory deficits, the frequency of cognitive impairments may occur in up to 30% of stroke survivors at 3 months. This impairment may be confounded by preexisting cognitive decline or dementia. By contrast, cognitive changes and dementia are widely recognized in familial forms of stroke, such as cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Several factors, including type of stroke, recurrent episodes, the site and laterality of the lesion(s), volume of cerebral infarction, medial temporal lobe atrophy, and coexistent neurodegenerative pathology predict the degree of impairment. Aphasia, diabetes mellitus, atrial fibrillation, and depression are listed among other biologic factors that further exacerbate cognition and affect long-term survival. There is no clear consensus whether genetic factors, such as the apolipoprotein E e4 allele or angiotensin converting enzyme gene polymorphisms, modify cognitive changes or stroke outcome. Although several neurotransmitter systems may be affected in post-stroke dementia, the amelioration of cholinergic function is a worthy target.

Cognition Disorders↗
PubMed2001

Quality of life for people with dementia living in residential and nursing home care: the impact of performance on activities of daily living, behavioral and psychological symptoms, language skills, and psychotropic drugs.

Many people with dementia reside in care facilities. Little is known about how key parameters impact upon their quality of life (QOL). All 209 people with dementia in six facilities received a standardized assessment (Neuropsychiatric Inventory [NPI], Barthel Scale, psychotropic drugs). One hundred twelve residents were assessed using Dementia Care Mapping, an observational method for QOL indices. Lower performance on activities of daily living (reduced well-being [WB] r = +0.39, p < .0001; social withdrawal [SW] r = +0.42, p < .0001; engagement in activities [EA] r = +0.31, p = .001) and taking psychotropics (WB 2.5 vs. 3.2, t = 2.3, p = .02; SW 11.4% vs. 2.7%, t = 3.0, p = .004; EA 56.5% vs. 71.9%; t = 3.5, p = .001) were associated with reduced QOL, but symptoms from the NPI were not. More focused prescribing of psychotropics and better staff training are essential.

Activities of Daily Living↗