Neuropsychological differentiation between Alzheimer's disease and dementia with Lewy bodies in a memory clinic.

OBJECTIVE: The aim of this study was to identify a useful neuropsychological instrument for making a differential clinical diagnosis between Alzheimer's disease (AD) and dementia with Lewy bodies (DLB). METHODS: We examined 402 AD and 38 DLB patients with neuropsychological tests that covered general cognition, frontal lobe cognitive function, non-verbal abstract reasoning, working memory and attention, and verbal memory. Discriminant analysis using a stepwise method was performed to identify the measures best able to discriminate between AD and DLB. RESULTS: The AD patients performed significantly worse than the DLB patients on orientation to time, delayed recall subtests on the Mini-Mental State Examination, and logical memory subtests 1 and 2 of the Revised Wechsler Memory Scale. The DLB patients performed significantly worse than the AD patients on the attention, repetition, and pentagon copying subtests of the Mini-Mental State Examination, the constructional praxis subtests of the Alzheimer's Disease Assessment Scale-cognitive component-Japanese version, the Frontal Assessment Battery total score, Raven's Coloured Progressive Matrices (RCPM) sets A, AB, and B, and backward digit span. Discriminant analyses between AD and DLB established the key variables as Logical Memory 1, Logical Memory 2, backward digit span, RCPM, and delayed recall on the Mini-Mental State Examination. We inferred the AD-DLB discriminant index from the following discriminant analyses: AD-DLB discriminant index = (Backward digit span score + RCPM set B score) - (Logical Memory 1 score + Logical Memory 2 score), which offered a highly favourable value for diagnostic utility. CONCLUSIONS: The AD-DLB discriminant index, consisting of backward digit span, RCPM set B, and logical memory 1 and 2, is useful to differentiate between AD and DLB.

Videofluorographic observations on swallowing in patients with dysphagia due to neurodegenerative diseases.

We examined three intervention methods for their efficacy in preventing aspiration in 25 patients with Parkinson's disease (PD) and 23 patients with degenerative cerebellar ataxia (CA). On videofluoroscopic examination. 13 patients with PD (52%) and 7 patients with CA (30.4%) showed aspiration. In all PD patients and 5 patients with CA, no aspiration was observed after changing the food form. With the chin down posture and supraglottic swallow techniques, no aspiration was observed in only 1 PD patient. Among 7 patients with CA, the chin down posture and supraglottic swallow techniques resulted in the disappearance of aspiration in 4 patients. This indicates that changing the food form (ex. jelly) was effective in preventing aspiration in both PD and CA patients with a history of aspiration. In addition, the chin down posture and supraglottic swallow techniques were effective in preventing aspiration in CA patients with good sitting-position balance and cervical control.

Visual hallucination in Parkinson's disease with FDG PET.

To determine the characteristics of cerebral glucose metabolism in Parkinson's disease patients with visual hallucinations, group comparison studies using [18F]fluorodeoxyglucose positron emission tomography were performed. Nondemented Parkinson's disease patients in advanced stages were classified into two groups: (1) patients without visual hallucinations; (2) patients with visual hallucinations. Compared to patients without hallucinations, the relative regional cerebral glucose metabolic rate was greater in the frontal areas in patients with visual hallucinations, and the increase reached a significant level in the left superior frontal gyrus. Relative frontal hypermetabolism may be a feature of Parkinson's disease patients with visual hallucinations.

Cognitive- and motor-related regions in Parkinson's disease: FDOPA and FDG PET studies.

OBJECTIVE: Using 6-[(18)F]fluoro-L-dopa (FDOPA) and [(18)F]fluorodeoxyglucoce (FDG) positron emission tomography (PET), multiple regression analyses were performed to determine the specific brain regions that are related to cognitive and motor symptoms in nondemented patients with Parkinson's disease. METHODS: Spatially normalized images of FDOPA influx rate constant (Ki) values and relative regional cerebral metabolic rates for glucose (rrCMRglc) were created. Raven's Coloured Progressive Matrices (RCPM) scores and the Unified Parkinson's Disease Rating Scale (UPDRS) motor scores were used to determine the patients' cognitive and motor functions, respectively. Multiple correlation analyses between the FDOPA and FDG images and the cognitive and motor scores were performed for each voxel. RESULTS: RCPM score was significantly positively correlated with the FDOPA Ki in the left hippocampus and with the rrCMRglc in the left middle frontal gyrus and right retrosplenial cortex. Motor function was significantly positively correlated with the FDOPA Ki in the bilateral striatum and with the rrCMRglc in association areas and primary visual cortex. The level of motor function was significantly inversely correlated with the FDOPA Ki in the anterior cingulate gyrus and with the rrCMRglc in bilateral primary motor cortex and right putamen. CONCLUSIONS: Changes of striatal FDOPA uptake and rrCMRglc in the primary motor cortex likely represent dysfunction in the motor system involving the corticobasal ganglia-thalamocortical loop. Change of FDOPA uptake in the anterior cingulate gyrus may be related to up-regulation of dopamine synthesis in surviving dopamine neurons. The regions where correlation with cognitive function was observed belong to a cognitive frontoparietal-hippocampal network.

Asymmetrical enhancement of middle-latency auditory evoked fields with aging.

We studied the effects of aging on middle-latency auditory evoked fields (P50m), and analyzed their interhemispheric differences. Magnetic responses following tone-burst stimuli to the right ear were measured in groups of 11 younger and 15 elderly subjects. The elderly subjects showed marked asymmetry in the P50m amplitudes. In the elderly group, the mean amplitude of the contralateral P50m was significantly larger (P<0.0005) than that of the ipsilateral P50m, while no asymmetry was shown in the younger group. The amplitude enlargement in the contralateral P50m showed significant correlation with age (R=0.60, P<0.005), while the ipsilateral P50m showed no correlation with age. These results suggest that the contralateral and ipsilateral auditory pathways are affected differently by ageing.

Striatal and extrastriatal dysfunction in Parkinson's disease with dementia: a 6-[18F]fluoro-L-dopa PET study.

We investigated the relative differences in dopaminergic function through the whole brain in patients with Parkinson's disease without dementia (PD) and with dementia (PDD) using 6-[18F]fluoro-L-dopa (18F-dopa) PET and a voxel-by-voxel analysis. The 10 PD and 10 PDD patients were equivalently disabled, having mean scores of 3.2 +/- 0.6 and 3.2 +/- 0.7, respectively, on the Hoehn and Yahr rating scale. 18F-dopa influx constant (Ki) images of those patients and 15 normal age-matched subjects were transformed into standard stereotactic space. The significant differences between the groups (expressed in mean regional Ki values) were localized with statistical parametric mapping (SPM) on a voxel-by-voxel basis. Compared with the normal group, SPM localized declines of the 18F-dopa Ki bilaterally in the putamen, the right caudate nucleus and the left ventral midbrain for the PD group (P < 0.01, corrected). Compared with the normal group, the PDD group showed reduced 18F-dopa Ki bilaterally in the striatum, midbrain and anterior cingulate area (P < 0.01, corrected). A relative difference in 18F-dopa uptake between PD and PDD was the bilateral decline in the anterior cingulate area and ventral striatum and in the right caudate nucleus in the PDD group (P < 0.001, corrected). Accordingly, we conclude that dementia in PD is associated with impaired mesolimbic and caudate dopaminergic function.

Progression and prognosis in multiple system atrophy: an analysis of 230 Japanese patients.

We investigated the disease progression and survival in 230 Japanese patients with multiple system atrophy (MSA; 131 men, 99 women; 208 probable MSA, 22 definite; mean age at onset, 55.4 years). Cerebellar dysfunction (multiple system atrophy-cerebellar; MSA-C) predominated in 155 patients, and parkinsonism (multiple system atrophy-parkinsonian; MSA-P) in 75. The median time from initial symptom to combined motor and autonomic dysfunction was 2 years (range 1-10). Median intervals from onset to aid-requiring walking, confinement to a wheelchair, a bedridden state and death were 3, 5, 8 and 9 years, respectively. Patients manifesting combined motor and autonomic involvement within 3 years of onset had a significantly increased risk of not only developing advanced disease stage but also shorter survival (P < 0.01). MSA-P patients had more rapid functional deterioration than MSA-C patients (aid-requiring walking, P = 0.03; confinement to a wheelchair, P < 0.01; bedridden state, P < 0.01), but showed similar survival. Onset in older individuals showed increased risk of confinement to a wheelchair (P < 0.05), bedridden state (P = 0.03) and death (P < 0.01). Patients initially complaining of motor symptoms had accelerated risk of aid-requiring walking (P < 0.01) and confinement to a wheelchair (P < 0.01) compared with those initially complaining of autonomic symptoms, while the time until confinement to a bedridden state and survival were no worse. Gender was not associated with differences in worsening of function or survival. On MRI, a hyperintense rim at the lateral edge of the dorsolateral putamen was seen in 34.5% of cases, and a 'hot cross bun' sign in the pontine basis (PB) in 63.3%. These putaminal and pontine abnormalities became more prominent as MSA-P and MSA-C features advanced. The atrophy of the cerebellar vermis and PB showed a significant correlation particularly with the interval following the appearance of cerebellar symptoms in MSA-C (r = 0.71, P < 0.01, r = 0.76 and P < 0.01, respectively), but the relationship between atrophy and functional status was highly variable among the individuals, suggesting that other factors influenced the functional deterioration. Atrophy of the corpus callosum was seen in a subpopulation of MSA, suggesting hemispheric involvement in a subgroup of MSA patients. The present study suggested that many factors are involved in the progression of MSA but, most importantly, the interval from initial symptom to combined motor and autonomic dysfunction can predict functional deterioration and survival in MSA.