Diffusion tensor imaging in Alzheimer's disease and dementia with Lewy bodies

White matter changes have been investigated in Alzheimer's disease (AD) in a number of studies using diffusion imaging. Fewer studies have investigated dementia with Lewy bodies (DLB). We used diffusion-weighted magnetic resonance imaging (MRI) and high-resolution (0.3 mm in-plane) coronal 3T MRI of the medial temporal lobe in 16 subjects with AD, 16 with DLB and 16 similarly aged healthy subjects. We found increased mean diffusivity in the temporal lobe of AD, and reduced fractional anisotropy (FA) in a small cluster in the right postcentral gyrus region in the DLB group. Mean FA in this cluster correlated with UPDRS (Unified Parkinson's Disease Rating Scale) motor score. We had previously reported reduced visibility in the AD group of a dark appearing layer of the hippocampus in the high-resolution images. In an SPM analysis on all subjects, there were significant clusters of reduced FA in the corpus callosum, fornix and stria terminalis that correlated with the visual rating of the hippocampus. These results suggest that changes to the hippocampus are associated with structural changes to the white matter fibres of the hippocampus output, and that changes in motor function are associated with changes in white matter underlying somatosensory cortex.     

Diffusion tensor imaging in Alzheimer's disease and dementia with Lewy bodies

White matter changes have been investigated in Alzheimer's disease (AD) in a number of studies using diffusion imaging. Fewer studies have investigated dementia with Lewy bodies (DLB). We used diffusion-weighted magnetic resonance imaging (MRI) and high-resolution (0.3 mm in-plane) coronal 3T MRI of the medial temporal lobe in 16 subjects with AD, 16 with DLB and 16 similarly aged healthy subjects. We found increased mean diffusivity in the temporal lobe of AD, and reduced fractional anisotropy (FA) in a small cluster in the right postcentral gyrus region in the DLB group. Mean FA in this cluster correlated with UPDRS (Unified Parkinson's Disease Rating Scale) motor score. We had previously reported reduced visibility in the AD group of a dark appearing layer of the hippocampus in the high-resolution images. In an SPM analysis on all subjects, there were significant clusters of reduced FA in the corpus callosum, fornix and stria terminalis that correlated with the visual rating of the hippocampus. These results suggest that changes to the hippocampus are associated with structural changes to the white matter fibres of the hippocampus output, and that changes in motor function are associated with changes in white matter underlying somatosensory cortex.     

Neurofilament-immunoreactive neurons in Alzheimer's disease and dementia with Lewy bodies

The cortical neurons thought to be selectively affected in dementia with Lewy bodies (DLB) are those containing nonphosphorylated 200-kDa neurofilament (NF) protein. As these neurons are largely spared in Alzheimer's disease (AD), DLB and AD may impact on different cortical neuronal populations. The present study quantifies the NF-containing neurons in frontal and temporal cortex of 8 AD, 8 DLB, and 8 control cases. Formalin-fixed paraffin-embedded tissue was immunohistochemically stained with antibodies against nonphosphorylated and phosphorylated NF. Immunoreactive neurons were quantified by areal fraction analysis and corrected for cortical volume. As expected, nonphosphorylated and phosphorylated NF accumulated in the pathological hallmarks of AD and DLB. However, rather than a decrease in NF-containing neurons, a doubling of this population was observed in DLB, compared with AD and controls. This increased number of cortical NF-containing neurons reveal novel widespread cortical changes, beyond those explained by Lewy body formation, that are specific for DLB.     

EEG findings in dementia with Lewy bodies and Alzheimer's disease

OBJECTIVES: To evaluate the role of the EEG in the diagnosis of dementia with Lewy bodies (DLB). METHODS: Standard EEG recordings from 14 patients with DLB confirmed at postmortem were examined and were compared with the records from 11 patients with Alzheimer's disease confirmed at postmortem RESULTS: Seventeen of the total of 19 records from the patients with DLB were abnormal. Thirteen showed loss of alpha activity as the dominant rhythm and half had slow wave transient activity in the temporal lobe areas. This slow wave transient activity correlated with a clinical history of loss of consciousness. The patients with Alzheimer's disease were less likely to show transient slow waves and tended to have less marked slowing of dominant rhythm. CONCLUSIONS: The greater slowing of the EEG in DLB than in Alzheimer's disease may be related to a greater loss of choline acetyltransferase found in DLB. Temporal slow wave transients may be a useful diagnostic feature in DLB and may help to explain the transient disturbance of consciousness which is characteristic of the disorder.     

Quantitative electroencephalogram analysis in dementia with Lewy bodies and Alzheimer's disease

Clinicopathophysiological differences between dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) remain obscure. Our goals were to determine whether characteristic findings of electroencephalogram (EEG) power and coherence in DLB and a differential pathophysiological mechanism of quantitative EEG existed between DLB and AD. The group consisted of 15 patients with AD or DLB and 12 age-matched controls. Original EEG signals were recorded from 14 scalp electrodes positioned according to the International 10-20 System, using digitally linked earlobes as a reference. Although EEG power spectral analysis showed increasing EEG power density in patients with DLB in the delta and theta bands, such a difference did not exist in patients with AD. Compared with AD, the delta and theta band intrahemispheric coherence values in the fronto-temporo-central regions were higher in DLB. In the beta band, AD was lower than DLB in almost all temporo-centro-parieto-occipital regions. Comparing the mean power value between patients with/without donepezil treatment, there was a significantly lower EEG power density in the delta and theta bands in DLB subjects taking donepezil than in subjects not taking donepezil, whereas there was no significant difference in AD patients. These results suggest that cholinergic dysfunction is stronger in DLB than AD.     

Differentiating dementia with Lewy bodies from Alzheimer's disease and Parkinson's disease dementia: an update on imaging modalities

Journal of Neurology - Dementia with Lewy bodies is the second most common cause of neurodegenerative dementia after Alzheimer's disease. Dementia with Lewy bodies can provide a diagnostic...     

Functional imaging in Parkinson's disease and dementia with Lewy bodies

Functional imaging modalities (positron emission tomography, single photon emission tomography, magnetic resonance spectroscopy, and functional magnetic resonance) allow aspects of regional cerebral function to be evaluated in various neuropsychiatric disorders. This review will summarize the use of such techniques in current imaging studies involving Parkinson's disease and dementia with Lewy bodies, with respect to assessing regional changes, using them in differential diagnosis, and monitoring disease progression and treatment effects.     

Comparison of dementia with Lewy bodies to Alzheimer's disease and Parkinson's disease with dementia.

We compared the clinical and neuropsychological pattern of dementia with Lewy bodies (DLB) to Alzheimer's disease (AD) and Parkinson's disease with dementia (PD-d). Sixteen patients clinically diagnosed with DLB were compared with two groups of patients with PD-d (n = 15) and AD (n = 16) matched for level of dementia. Isolated cognitive impairment was the most common form of presentation in AD (93.8%) and DLB (31.3%) groups, while parkinsonism was in 100% of PD-d subjects. Psychoses associated with cognitive impairment at the beginning of the disease were more frequent in DLB patients (31.3%) than in AD (6.3%) and PD-d (0%) groups. There were no significant differences in Unified Parkinson Disease Rating Scale motor-subscale scores between DLB and PD-d patients. DLB and PD-d patients performed significantly worse on attentional functions and better on memory tests than AD. DLB patients also showed lower scores than AD subjects on visual memory, visuoperceptive, and visuoconstructive tests. No significant differences were found between PD-d group and DLB subjects on any neuropsychological test. We were unable to find any differences in cognitive tasks between PD-d and DLB subjects. Clinical features and neuropsychological deficiencies of DLB (attentional, visuoperceptive, and visuoconstructive deficits) and PD (attentional deficits) compared to AD (amnesic syndrome) can contribute to accurate identification of these entities and to the understanding of the neuropathological and neurochemical substrate underlying these diseases.     

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.     

High resolution imaging of the medial temporal lobe in Alzheimer's disease and dementia with Lewy bodies

We used high resolution (0.3 mm in-plane) coronal 3T magnetic resonance (MR) imaging of the medial temporal lobe in 16 subjects with Alzheimer's disease (AD), 16 with dementia with Lewy bodies (DLB), and 16 similarly aged healthy subjects. On the anterior section of the hippocampus body, regions of interest were manually drawn blind to diagnosis on the CA1, CA2, and CA3/4 subregions, and the width of the subiculum and entorhinal cortex was measured. Controlling for intracranial volume, age, and years of education, we found the subiculum thickness was significantly reduced in AD (2.03 ± 0.29 mm) compared to both control (2.37 ± 0.28 mm, p = 0.008) and DLB (2.35 ± 0.24 mm, p = 0.001) subjects. The area of CA1 was likewise reduced in AD compared to controls and DLB. In the hippocampus images, a hypointense line is visible between CA1 and CA3/4. This line was significantly less distinct in AD, suggesting disease related changes to this region. Future studies should investigate whether subiculum thickness or the hypointense line could be a diagnostic feature to help discriminate AD from DLB.     

Quantifying fluctuation in dementia with Lewy bodies, Alzheimer's disease, and vascular dementia

BACKGROUND: Case reports and clinical observations suggest that fluctuating cognition (FC) is common in the major dementias, particularly dementia with Lewy bodies (DLB), where it is one of three core clinical diagnostic features. OBJECTIVES: To examine the frequency, characteristics, and diagnostic utility of FC in dementia using clinical, attentional, and EEG markers. Method:- A total of 155 subjects (61 with AD, 37 with DLB, 22 with vascular dementia [VaD], 35 elderly controls) received clinical evaluation for FC using a semiquantified measure applied by experienced clinicians and 90-second cognitive choice reaction time (CRT) and vigilance reaction time (VIGRT) trials. Forty subjects also received an evaluation of mean EEG frequency across 90 seconds. RESULTS: Patients with DLB had a greater prevalence and severity of FC than did patients with AD or VaD rated using clinical, attentional, and EEG measures. The 90-second cognitive and EEG trials demonstrated that FC occurs on a second-to-second basis in patients with DLB. Patients with VaD had a higher prevalence of FC than did those with AD, although the profile of FC was different from that expressed by DLB cases. Optimal cutoff values on the clinical scale achieved good discrimination between the dementia groups (sensitivity 81%, specificity 92%, DLB versus AD; sensitivity 81%, specificity 82%, DLB versus VaD; sensitivity 64%, specificity 77%, VaD versus AD). CONCLUSION: Standardized assessment methods demonstrate that FC is significantly more common and severe in DLB than in other major dementias. The periodicity of FC is different in DLB and VaD cases, with important implications for the underlying causal mechanisms and for differential diagnosis.     

Diffusion tensor imaging in early Alzheimer's disease

Our aim was to investigate the extent of white matter tissue damage in patients with early Alzheimer disease (AD) using diffusion tensor magnetic resonance imaging (DTI). Although AD pathology mainly affects cortical grey matter, previous magnetic resonance imaging (MRI) studies showed that changes also exist in the white matter (WM). However, the nature of AD-associated WM damage is still unclear. Conventional and DTI examinations (b=1000 s/mm(2), 25 directions) were obtained from 12 patients with early AD (Mini Mental State Examination [MMSE] score=27, Grober and Buschke test score=33.2, digit span score=5.6) and 12 sex- and age-matched volunteers. The right and left mean diffusivity (MD) and fractional anisotropy (FA) of several WM regions were pooled in each patient and control, and compared between the two groups. Volumes of the whole brain and degree of atrophy of the temporal lobe were compared between the two groups. In AD, MD was increased in the splenium of the corpus callosum and in the WM in the frontal and parietal lobes. FA was bilaterally decreased in the WM of the temporal lobe, the frontal lobe and the splenium compared with corresponding regions in controls. Values in other areas (occipital area, superior temporal area, cingulum, internal capsule, and genu of the corpus callosum) were not different between patients and controls. No correlations were found between the MMSE score and the anisotropy indices. Findings of DTI reveal abnormalities in the frontal and temporal WM in early AD patients. These changes are compatible with early temporal-to-frontal disconnections.     

Rates of cognitive decline in Alzheimer's disease and dementia with Lewy bodies

Increased interest in types of dementia has developed as more cases are identified in aging populations. Here we compare the rates of cognitive decline over time in three groups with dementia from the University of Western Ontario Dementia Study: Alzheimer's disease (AD), dementia with Lewy bodies and a group with both AD and Lewy bodies. All diagnoses were verified by autopsy using standard diagnostic methods. Cognitive impairment was measured with the Extended Scale for Dementia (ESD). Members of each group with dementia were age and sex matched with individuals without dementia as controls. The 15 cases of AD, 7 cases with Lewy bodies and 8 cases with both conditions were all free of significant vascular disease. Linear regression was used to determine the rate of changes in ESD scores over time in months. All three control groups showed no change in cognitive status over time. As expected, all groups with dementia showed progressive cognitive impairment. Analysis of the slope parameter showed that all groups deteriorated at the same rate of approximately 2 ESD points per month. Quadratic models fit better than simple linear models in all groups. Results suggest that the final rate of cognitive decline in dementia may not necessarily reflect the underlying cause.     

Differences in clinical course between dementia with Lewy bodies and Alzheimer's disease

Background and purpose:  To investigate whether there may be differences in the clinical course and changes in cognitive progression between dementia with Lewy bodies (DLB) and Alzheimer's disease (AD).
Methods:  We compared the time from the first visit to endpoints (discontinuation of visits because of admission, death, or institutionalization) between 56 patients with DLB and 111 patients with AD. Mini-Mental State Examination (MMSE) scores of patients were every 12 months examined up to 60 months.
Results:  Dementia with Lewy bodies had a significantly shorter time to reaching endpoints than those with AD (median time; 40 months vs. 52 months, P  < 0.0001). The proportion of admission (or death) was significantly higher in DLB than in AD (30% vs. 14%, P  < 0.05), while the difference in institutionalization in nursing homes did not reach statistical significance (25% vs. 17%). Rates of longitudinal MMSE score decline for DLB and AD groups were equivalent.
Conclusion:  Dementia with Lewy bodies had a greater risk of admission (or death) because of most commonly fall-related injuries and bronchopneumonia than AD, but the two groups did not differ in rate of cognitive decline.     

Patients with Alzheimer's disease and dementia with Lewy bodies mistaken for Creutzfeldt-Jakob disease.

OBJECTIVES: To describe the clinical presentation of patients with Alzheimer's disease (AD) or dementia with Lewy bodies (DLB) who were suspected of having Creutzfeldt-Jakob disease (CJD) and to investigate whether current clinical diagnostic criteria cover these atypical forms of AD and DLB. METHODS: Brains from necropsy were examined for the diagnosis of CJD at the German reference centre for spongiform encephalopathies. Symptoms and signs in patients with suspected CJD in whom necropsy showed AD (n=19) or DLB (n=12) were analysed. Their data were compared with a group of patients with CJD (n=25) to determine overlapping and discriminating clinical features. All patients were classified according to clinical diagnostic criteria for CJD, AD, and DLB. RESULTS: Demented patients were suspected of having CJD if disease was rapidly progressing and/or focal neurological signs appeared and/or an EEG showed sharp wave complexes. Myoclonus and limb rigidity were the most common neurological signs in all three dementias. DLB was not suspected in any patient, although patients with DLB showed parkinsonism (58%) and fluctuations (58%). Periodic sharp wave complexes (PSWCs) in EEG typical of CJD were found in five patients with AD and one patient with DLB. 14-3-3 Protein in CSF was detected in 20 patients with CJD, in two patients with AD, but not in any patient with DLB. Although most patients with DLB or AD met the clinical criteria for their respective diagnosis (74% and 90%), they also fulfilled criteria for CJD (42% and 58%). CONCLUSIONS: In patients with rapidly progressive dementia and focal neurological signs, CJD should be the first line diagnosis. Facing the triad dementia, myoclonus, and rigidity, AD should be considered if the disease course is longer and DLB is the differential diagnosis if parkinsonism or fluctuations are present. Findings on EEG or CSF typical of CJD do not exclude AD or DLB.     

Synaptophysin immunoreactivity in Pick's disease: comparison with Alzheimer's disease and dementia with Lewy bodies

Frontotemporal lobe atrophy is a hallmark of Pick's disease (PiD), however, the underlying pathobiology of the neuronal losses is unknown. Synaptic losses have been described in Alzheimer's disease (AD) and correlate with the severity of dementia, however few studies of synaptic integrity have been done to determine whether synaptic loss also contributes to symptoms in non-AD dementias. To begin to assess synaptic integrity in other types of dementia, we examined the site of termination of the hippocampal perforant pathway, the major source of afferent tracts to the hippocampus. We determined immunoreactivity for the synaptic-terminal specific protein synaptophysin in the outer molecular layer of the hippocampal dentate gyrus (OMDG) in eight PiD, nine AD, nine dementia with Lewy bodies (DLB), and seven control cases. Quantitative data were obtained using an Image-Pro automated image analysis system. In AD and PiD, synaptophysin immunoreactivity was visibly reduced in the OMDG Densitometric analysis confirmed that there were statistically significant differences among groups in synaptophysin immunoreactivity when comparing the OMDG to the adjacent inner molecular layer of the hippocampal dentate gyrus (IMDG) (p = 0.002). These differences were present between PiD and both the control and DLB groups. The AD group also showed a reduction in synaptophysin immunoreactivity compared with DLB and control groups. In contrast, perforant pathway synaptic losses in DLB were minimal. Our data supports the hypothesis that focal synaptic losses occur in PiD and AD and may contribute to the cognitive deficits in both conditions.