Proton magnetic resonance spectroscopy detects a relative decrease of N-acetylaspartate in the hippocampus of patients with dementia with Lewy bodies.

BACKGROUND AND PURPOSE: To characterize the cerebral metabolic changes in dementia with Lewy bodies patients. METHODS: The metabolic ratios of NAA/Cr and Cho/Cr in bilateral hippocampus were determined by proton magnetic resonance spectroscopy in 8 patients and 8 age-matched healthy controls. RESULTS: Dementia with Lewy bodies patients showed significantly lower NAA/Cr ratios in bilateral hippocampus, while the Cho/Cr ratio did not differ from the control group. CONCLUSIONS: Our data show relatively decrease of N-acetylaspartate in the hippocampus of patients with early or intermediate stage DLB. Hence, damage of neurons seems to be an early alteration in DLB.     

Proton magnetic resonance spectroscopy in frontotemporal dementia

This study of frontotemporal dementia (FTD) was carried out to determine whether MR spectroscopy can provide an in vivo marker for the neuronal loss and gliosis that occur in this condition. We compared spectra in frontal and temporal regions known to be affected early in the course of the disease with spectra in the parietal lobe that is spared until late stages of FTD. We were interested in the relative concentrations of two compounds, NAA (a marker of neuronal integrity) and mI (a marker of gliosis), expressed as ratios to creatine (a relatively stable brain constituent). MR spectroscopy was performed on the temporal, parietal, and anterior cingulate cortices of five patients with the established semantic dementia form of FTD, two patients with the frontal form of FTD and 13 age matched controls. Structural MRI and neuropsychometry were also performed. Patients with FTD had reduced NAA/Cr in frontal and temporal, but not parietal lobes. The two patients with the frontal form of FTD had increased mI/Cr in their cingulate cortices. These data show for the first time that MR spectroscopy can reveal regionally selective abnormalities in patients with FTD. This opens up the possibility of using MR spectroscopy as a clinical tool to identify earlier presentations of the condition.     

Proton magnetic resonance spectroscopy of the brain in dementia

Proton magnetic resonance spectroscopy (MRS) allows accurate and noninvasive biochemical assay of living tissues. In vivo measurements provided by MRS have greatly enhanced our understanding of the pathophysiology of dementia. Increases in choline and myo-inositol (markers of membrane turnover) have been demonstrated in several studies on patients with Alzheimer's disease (AD), suggesting the presence of a significant cellular membrane (and glial) pathology in this disorder. Large decreases in brain N-acetylaspartate (NAA) (a marker of neuroaxonal integrity) are commonly seen in AD as well as in other forms of dementia in cerebral gray and white matter, indicating the presence of significant axonal damage. Since greater NAA decreases have been demonstrated in brains of patients with clinically more severe disease, NAA could provide an index relevant to patients' clinical status. Brain metabolic changes can be independent of abnormalities detected by conventional magnetic resonance imaging (MRI), since proton MRS may show a normal metabolic pattern in patients with mild neurological impairment and severe MRI abnormalities. However, quantitative measurements of regional brain volumes can be useful in the diagnosis of dementia. Thus, proton MRS, alone or combined with new quantitative magnetic resonance techniques, can provide sensitive indices able to monitor disease progresson or effects of drug therapy.     

Microbleeds in dementia with Lewy bodies

Journal of Neurology - Microbleeds are associated with the development of dementia in older people and are common in Alzheimer’s disease (AD). Their prevalence and clinical importance in...     

Lewy bodies and dementia

The discovery of widely distributed Lewy bodies (LBs) in the brains of patients with dementia has stimulated much clinical and pathologic inquiry. This clinico-pathologic syndrome is now referred to as dementia with Lewy bodies (DLB). Diagnostic criteria for DLB proposed at a workshop in 1995 are receiving detailed scrutiny. The criteria are complex to apply, and appear to have high specificity, but variable sensitivity. Neuropathologic studies have been aided by the development of probes against a-synuclein, a key component of LBs. Widespread LBs in limbic or cortical areas contribute to dementia. Pharmacologic management of cognitive and behavioral symptoms in patients with DLB is being explored. There is evidence that cholinesterase inhibitors may have beneficial effects.     

Treatment of dementia with Lewy bodies

Dementia with Lewy bodies (DLB) is known for its partial resistance and hypersensitivity to some treatments, but DLB is treatable with cholinesterase inhibitors, sometimes better than in Alzheimer's disease. Cholinesterase inhibitors have a symptomatic effect on cognition and behavior. Nevertheless, new antipsychotics are sometimes also useful to manage psychotic symptoms. Although DLB patients respond less well to levodopa than patients with Parkinson's disease, 75 percent of DLB patients improve with levodopa, which is the best-tolerated dopaminergic agent. Nonpharmacological strategies include speech therapy, physiotherapy, psychotherapy, and educational support groups for care givers.     

Neuroimaging of dementia with Lewy bodies

Dementia with Lewy bodies (DLB) is a relative newcomer to the field of late-life dementia. Although a diversity of imaging methodologies is now available for the study of dementia, these have been applied most often to Alzheimer's disease (AD). Studies on DLB, although fewer, have yielded fascinating and important insights into the underlying pathophysiology of this condition and allowed clinical differentiation of DLB from other dementias. Imaging research on DLB has had significant ramifications in terms of raising the profile of DLB and helping define it as a distinctive and separate disease entity from AD.     

The electroencephalogram in dementia with Lewy bodies

OBJECTIVES: Dementia with Lewy bodies (DLB) is the second commonest neurodegenerative cause of dementia. While there is consensus on the clinical diagnostic criteria for DLB, the use of EEG to increase the diagnostic sensitivity has not been substantiated. MATERIAL AND METHODS: We studied the resting EEG findings in 18 consecutive patients with DLB and compared them with a control group of 20 patients with "probable" Alzheimer's disease (AD). We aimed to evaluate the use of EEG in a representative sample of patients with DLB. RESULTS: All patients with DLB fulfilled accepted clinical criteria for DLB. The DLB group had a more severe dementia than the AD group, as measured by the Mini-Mental State Examination (MMSE) test (DLB mean MMSE 9.4 and AD mean MMSE 17.2) despite a similar duration of overall severity of illness. The EEG was slow in both groups, predominantly in the 4-7 Hz range. Although there was no statistically significant difference in the EEG findings between the DLB and AD groups, there was a correlation between the EEG score and MMSE score (Spearman Rank correlation rs = -0.61, P < 0.001). CONCLUSION: These findings suggest that although patients with DLB have a more aggressive course than AD, EEG abnormalities do not differ in the 2 groups. However, we believe the EEG provides important supporting diagnostic information in DLB.     

Autonomic dysfunctions in dementia with Lewy bodies

Twenty-nine cases of both clinically and neuropathologically diagnosed dementia with Lewy bodies (DLB) were retrospectively examined for autonomic symptoms. Twenty-eight cases showed some kind of autonomic dysfunction. Urinary incontinence (97 %) and constipation (83 %) were the two most common. Although urinary retention and episodic hypotension causing syncopal attacks were less common, the frequency was still high (28 % each). There were 18 cases (62 %) with severe autonomic failure. These 28 cases showed similar tendencies, with no significant differences between the subtypes of DLB (brainstem, limbic, and neocortical types or common and pure forms). We found that DLB of all pathological subtypes exhibits some kind and level of autonomic symptoms. Received: 20 August 2002, Received in revised form: 12 November 2002, Accepted: 18 November 2002 Correspondence to Y. Horimoto     

Visuoperceptual impairment in dementia with Lewy bodies

BACKGROUND: In dementia with Lewy bodies (DLB), vision-related cognitive and behavioral symptoms are common, and involvement of the occipital visual cortices has been demonstrated in functional neuroimaging studies. OBJECTIVES: To delineate visuoperceptual disturbance in patients with DLB in comparison with that in patients with Alzheimer disease and to explore the relationship between visuoperceptual disturbance and the vision-related cognitive and behavioral symptoms. DESIGN: Case-control study. SETTING: Research-oriented hospital. PATIENTS: Twenty-four patients with probable DLB (based on criteria of the Consortium on DLB International Workshop) and 48 patients with probable Alzheimer disease (based on criteria of the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association) who were matched to those with DLB 2:1 by age, sex, education, and Mini-Mental State Examination score. MAIN OUTCOME MEASURES: Four test items to examine visuoperceptual functions, including the object size discrimination, form discrimination, overlapping figure identification, and visual counting tasks. RESULTS: Compared with patients with probable Alzheimer disease, patients with probable DLB scored significantly lower on all the visuoperceptive tasks (P<.04 to P<.001). In the DLB group, patients with visual hallucinations (n = 18) scored significantly lower on the overlapping figure identification (P = .01) than those without them (n = 6), and patients with television misidentifications (n = 5) scored significantly lower on the size discrimination (P<.001), form discrimination (P = .01), and visual counting (P = .007) than those without them (n = 19). CONCLUSIONS: Visual perception is defective in probable DLB. The defective visual perception plays a role in development of visual hallucinations, delusional misidentifications, visual agnosias, and visuoconstructive disability charcteristic of DLB.     

Capgras' syndrome in dementia with Lewy bodies

We report the occurrence of Capgras' syndrome, or the delusion of doubles, in a patient with dementia with Lewy bodies. The patient believed that several similar-looking impostors had replaced his wife of over 50 years. Uncharacteristically, he adopted a friendly attitude with these impostors. This unusual convivial reaction to the impostors may result from differential involvement of the dual visual pathways processing facial recognition and emotional responses to faces. The delusion resolved spontaneously, coincident with worsening of the dementia. In a retrospective chart review of 18 autopsy-confirmed cases of dementia with Lewy bodies, delusions were reported in 5 subjects (27.8%), of whom 1 had misidentification delusions much like Capgras' syndrome.     

Activated microglia in dementia with Lewy bodies

To investigate the role of cerebral inflammation in dementia with Lewy bodies (DLB), activated microglial cells were quantified in postmortem brain tissue. Patients with pure DLB (LB but no AD pathology) had significantly greater numbers of cells than nondemented control subjects, but fewer than patients with either pure AD or DLB combined with AD. There was a positive correlation between the numbers of activated microglia and LB in different brain regions. This study demonstrates the presence of significant inflammation in DLB, even in the absence of AD pathology.     

Proton magnetic resonance spectroscopy of patients with parkinsonism

We studied cerebral metabolism in 82 patients with nonfamilial parkinsonism, including Parkinson's disease (PD; n = 23), progressive supranuclear palsy (PSP; n = 12), corticobasal degeneration (CBD; n = 19), multiple systemic atrophy (MSA; n = 18) and vascular parkinsonism (VP; n = 10) by using proton magnetic resonance spectroscopy ((1)H-MRS), which allowed noninvasive measurement of signal intensities from N-acetylasparate (NAA), choline-containing compounds (CHO) and creatine plus phosphocreatine (CRE). As compared to normal controls, patients with PSP, CBD, MSA and VP, but not PD, had significant reduction of the NAA/CRE ratio in the frontal cortex, whereas patients with PSP, CBD, MSA and PD, but not VP, had significant reduction of the NAA/CRE ratio in the putamen. Patients with CBD had significant reduction of the NAA/CRE ratio in the frontal cortex and putamen as compared to patients with PD, MSA and VP. Patients with PSP showed a significant reduction of the NAA/CRE ratio in the putamen as compared with patients with PD and MSA. Patients with CBD showed clear asymmetry in the putamen as compared to controls and other patients. The reduction of the NAA/CRE ratio in the putamen correlated well with the severity of parkinsonism. (1)H-MRS may be useful in monitoring patients with various types of parkinsonism.