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Background and Aim Early clinical diagnosis of progressive supranuclear palsy (PSP) remains challenging. Aim We attempted to identify any sign or symptom to diagnose PSP earlier. Methods A total of 401 patients, 40 with PSP and 361 with other neurodegenerative disorders, were included. We followed these patients for at least 1 year since 2009. We reviewed the signs and symptoms of patients with PSP in a standardized manner, and observed four manifestations: “vertical supranuclear gaze abnormality,” “movement disorders,” “pseudobulbar palsy” and “dementia of frontal type.” Features, such as symmetric parkinsonism, freezing of gait, postural instability, dysarthria and/or dysphagia, or dementia of frontal type, were considered core clinical features. Results In patients with PSP, “movement disorders” was the most common manifestation, whereas “vertical supranuclear gaze abnormality” was uncommon during the early disease course. A total of 16 patients fulfilled the National Institute for Neurological Disorders and Stroke and Society for PSP criteria for possible PSP at their first clinic visit. Of the remaining 24 patients, 15 presented with one or more core clinical features before fulfilling the criteria for possible PSP; nine patients had a clinical diagnosis of PSP but never fulfilled the criteria. A total of 49 of the 361 patients with other neurodegenerative disorders had core clinical features. A comparison showed that freezing of gait differentiated the groups the best over the disease course. Conclusion Freezing of gait is an early feature that might improve the clinical diagnosis of PSP, whereas vertical supranuclear gaze abnormality is not.

International audience; Objective : Glucocerebrosidase gene (GBA) variants that cause Gaucher disease are associated with Parkinson disease (PD) and dementia with Lewy bodies (DLB). To investigate the role of GBA variants in multiple system atrophy (MSA), we analyzed GBA variants in a large case–control series.Methods : We sequenced coding regions and flanking splice sites of GBA in 969 MSA patients (574 Japanese, 223 European, and 172 North American) and 1509 control subjects (900 Japanese, 315 European, and 294 North American). We focused solely on Gaucher-disease-causing GBA variants.Results : In the Japanese series, we found nine carriers among the MSA patients (1.65%) and eight carriers among the control subjects (0.89%). In the European series, we found three carriers among the MSA patients (1.35%) and two carriers among the control subjects (0.63%). In the North American series, we found five carriers among the MSA patients (2.91%) and one carrier among the control subjects (0.34%). Subjecting each series to a Mantel–Haenszel analysis yielded a pooled odds ratio (OR) of 2.44 (95% confidence interval [CI], 1.14–5.21) and a P-value of 0.029 without evidence of significant heterogeneity. Logistic regression analysis yielded similar results, with an adjusted OR of 2.43 (95% CI 1.15–5.37) and a P-value of 0.022. Subtype analysis showed that Gaucher-disease-causing GBA variants are significantly associated with MSA cerebellar subtype (MSA-C) patients (P = 7.3 × 10−3).Interpretation : The findings indicate that, as in PD and DLB, Gaucher-disease-causing GBA variants are associated with MSA.

Although dementia is increasingly recognized as a common feature in Parkinson's disease (PD), its pathological substrate remains unknown. We conducted cross-sectional and longitudinal brain perfusion SPECT analyses to explore changes during the course of developing dementia in PD. Fifty-five patients originally diagnosed with PD were imaged in the cross-sectional study. Twenty-one of these, nine without dementia and 12 with dementia (PDD), were included in the longitudinal study to observe perfusion changes during the course of their disease. Data were analyzed using three-dimensional stereotactic surface projection SPECT analysis. The UK Parkinson's Disease Society Brain Bank criteria were used to diagnose PD and the revised criteria for the clinical diagnosis of dementia with Lewy bodies for PDD. The cross-sectional study showed that patients with PDD had significantly reduced perfusion in the right posterior cingulate, the right precuneus and the left posterior cingulate area. In the longitudinal study, significantly reduced perfusion was observed in the left anterior frontal gyrus in PD without dementia, and in the right inferior parietal lobule in those that developed PDD. We suggest that a relationship exists between developing dementia in PDD and reduced perfusion in the posterior parietal area.

Aim: To identify factors associated with falling, we assessed the Tinetti Gait and Balance Scale (TGBS) for patients with Parkinson’s disease (PD) and atypical parkinsonism (AP), and assessed the Unified Parkinson’s Disease Rating Scale (UPDRS) for patients with PD. Methods: A cross sectional study was conducted in a university hospital, with the subject constituting 30 PD patients and 22 AP patients. Each item included in the TGBS and the UPDRS part III were scored in the clinical setting. Fallers were categorized if the patient experienced at least one fall in the prior six-month period. Results: Thirty-five patients were categorized as fallers. When comparing PD fallers and PD non-fallers, a subscore comprising a sum with ‘walk stance’ and ‘nudge on sternum’ in the TGBS showed a significant difference. Total UPDRS part III score indicated a significant difference during the medication ON period, whereas the difference was insignificant during the medication OFF period. The presence of dyskinesia or freezing of gait was not different. In addition, ‘walk stance’ only in the TGBS showed a significant difference between PD fallers and AP fallers. Conclusions: We concluded that ‘walk stance’ and ‘nudge on sternum’ in the TGBS may be useful for evaluating factors associated to falling in PD. ‘Walk stance’ item merits inclusion into routine assessment in PD in addition to UPDRS part III.

Background: Age-associated cognitive decline (AACD) is a predictor of dementia and highly prevalent among elderly people. Many elderly people with AACD also suffer from depressive moods. We studied, the effect of group work programs on the cognitive function and quality of life (QOL) of community-dwelling elderly people with AACD and/or mild depressive moods. Methods: Thirty-six subjects, with a mean age of 79.8 years, were included in this study. Twenty-one suffered from both AACD and mild depressive moods, nine suffered from mild depressive moods and six from AACD. Subjects were required to participate in a number of group work programs, such as music therapy, handicrafts and so on. They were assigned to one of two groups, and each participated in two 4-month sessions. In the first session, group 1 participated in the group work programs, while group 2 did not (control). In the second session, group 2 participated while group 1 did not. The effect of group work on elderly people with AACD (n = 27) and depressive moods (n = 31), was evaluated separately. Results: Improvement was observed in depressive moods and QOL (visual analogue scale of family relation, friendship and happiness, life satisfaction index) in subjects with cognitive impairment and depressive moods. The effect on cognitive function was shown only in elderly individuals suffering from depressive moods. The improvement in depressive moods and QOL seemed to be accompanied by an improvement in cognitive function but did not continue after completion of the group work program. Conclusion: Group work was shown to improve depressive moods, QOL and cognitive function; however, long-term effects require further examination.

We investigated regional cerebral blood flow (rCBF) using three-dimensional stereotactic surface projection (3D-SSP) analysis in 30 patients initially diagnosed as Parkinson's disease (PD), and compared differences in rCBF between patients with and without PD-related manifestations. 3D-SSP analysis of cerebral perfusion was performed by use of a control database. Compared to age-matched controls, there were multiple hypoperfusion areas in cases where the original diagnosis was PD. Temporal bases showed the lowest perfusion; frontal bases and medial parietal lobes the second; visual cortices the third; and parietal association areas exhibited the fourth lowest. During the clinical course, 10 of the patients suffered dementia, 9 had fluctuating cognition, and 19 experienced repeated visual hallucinations. Significant negative correlations were observed between dementia and the bilateral posterior cingulate area, and among fluctuating cognition and bilateral medial parietal lobes, parietal association areas, and dorsal occipital lobes. Repeated visual hallucinations did not show any correlation with any region of interest. We concluded that multiple hypoperfusion areas were observed in the 3D-SSP SPECT analysis. Although the presence of dementia showed a significant relationship with the bilateral posterior cingulate areas, perfusion in the frontal bases, temporal bases, or parietal lobes was markedly more reduced than that seen in the bilateral posterior cingulate areas.

We assessed the accuracy of clinical diagnosis of progressive supranuclear palsy (PSP, Steele-Richardson-Olszewski disease) and the validity of existing sets of clinical diagnostic criteria for PSP (see Appendix) using neuropathologically examined cases from the Queen Square Brain Bank for Neurological Disorders. Diagnosis of PSP was made by 40 different physicians, and 60 cases clinically diagnosed as PSP when last assessed in life were studied. In 47 cases (78%), the diagnosis of PSP was confirmed pathologically. False-positive diagnoses included Parkinson's disease with significant additional cortical Lewy body (n = 3) or Alzheimer (n = 1) pathology, multiple system atrophy (n = 4), and corticobasal degeneration, Pick's disease, motor neurone disease, cerebrovascular disease, and a sporadic case of frontotemporal dementia and parkinsonism linked to chromosome 17 (1 case each). Most cases of PSP were diagnosed accurately by neurologists at the final assessment. Although application of National Institute of Neurological Disorders and the Society for PSP possible category marginally improved the accuracy of initial clinical diagnosis, none of the existing operational criteria could significantly improve accuracy of the final clinical diagnosis.

It has been reported that up to 80% of patients clinically diagnosed as having progressive supranuclear palsy (PSP) may have arterial hypertension (HT). Because previous studies were performed on patients with presumed diagnosis of PSP, we tried to replicate these studies in a series of pathologically confirmed patients. Seventy-three patients with a neuropathological diagnosis of PSP autopsied at the Queen Square Brain Bank for Neurological Disorders in London were collected between 1989 and 1999. For the purpose of this study, patients were considered hypertensive if a blood pressure above 140/90 mm Hg was found in the clinical records. The prevalence of HT in PSP patients at the first and at the last visit during their neurological disease was compared with that found in a series of 21 normal controls who donated their brain to the same institution. Overall, 29 of 73 (39.7%) of the patients were recorded as having HT at the first visit during the disease course; this ratio increased to 42 of 73 (57.5%) at the last visit before death. When these figures were compared to the 21 normal controls (11 of 21 with HT, 52.4%), we were unable to find an increased prevalence of HT in PSP (odds ratio, 0.60; 95% confidence interval, 0.20-1.76). Therefore, HT does not represent an important clinical feature of this neurodegenerative disorder, although cerebrovascular disease can masquerade clinically as PSP.

Background: The aim of the present paper was to assess the prevalence of atherosclerotic aortic plaques in non-rheumatic atrial fibrillation and their relation to ischemic stroke. Although aortic plaques are frequently seen in the elderly, their significance remains unclear in relation to ischemic stroke in patients with atrial fibrillation. Methods: Transesophageal echocardiography was performed on 56 patients (age 61 ± 10 years) with atrial fibrillation. The aorta was divided into two segments (i.e. the proximal aorta that includes the ascending aorta and the aortic arch proximal to the ostium of the left subclavian artery, and the distal aorta that is the descending aorta distal to the left subclavian artery). Thickened intima = 3 mm in thickness was defined as aortic plaques. Results: Ischemic stroke was found in 14 of the 56 patients. Aortic plaques were detected in 25 of the 56 patients. All of these 25 patients had aortic plaques in the proximal aorta, and 17 of them also had aortic plaques in the distal aorta. Ischemic stroke was found in 11 of the 25 patients (44%) with aortic plaques, and three of the 31 patients (10%) without aortic plaques (P < 0.01). Conversely, aortic plaques were detected in 11 of the 14 patients (79%) with ischemic stroke, and in 14 of the 42 patients (33%) without (P < 0.01). The patients with ischemic stroke had a larger left atrium (47 ± 5 vs 43 ± 6 mm; P < 0.05) than those without. Aortic plaques were a correlate only of previous ischemic stroke (P < 0.05) by multiple logistic regression analysis. Conclusions: Atherosclerotic aortic plaques detected by transesophageal echocardio-graphy are a correlate of previous ischemic stroke in patients with non-rheumatic atrial fibrillation.

BACKGROUND: Several studies in older people have found a U-shaped or J-shaped association of blood pressure with mortality. The increased mortality associated with the lowest levels of blood pressure in older people have been explained by concurrent illnesses and frailty, but previous studies used blood pressure measured on a single occasion. Such a casual value is different from the long-term average of blood pressure. We investigated the relation between the average level of 5-day consecutive home blood pressure and mortality in older people while adjusting for potential confounding factors including morbidity and frailty at baseline. METHODS: In 1992, 1186 community residents of a rural Japanese town, Kahoku, aged 65 or older, measured their blood pressure in their homes 20 times (four times per day, 5 consecutive days). The mean value of the 20 measurements was used to examine the association between home BP and subsequent 4-year mortality. A proportional hazards model was fitted while adjusting for activities of daily living impairment, medical history, antihypertensive medication, smoking, use of alcohol, and depression. RESULTS: A total of 134 persons died during the four-year follow-up period. There was no significant evidence that frailty is more prevalent in the lowest or highest systolic BP group than in intermediate groups. A U-shaped association between the average level of home systolic blood pressure and mortality was found in men while adjusting for potential confounding factors, including morbidity and frailty. We also showed the U-shaped curve of the association of systolic BP with all cause and noncardiovascular mortality in the whole population and the linear association of systolic BP with cardiovascular mortality. CONCLUSIONS: We showed a U-shaped association between the average level of systolic blood pressure measured at home and mortality in older men while adjusting for potential confounding factors including morbidity and frailty. Not only high home systolic BP, but also low home systolic BP, is an independent risk factor for mortality in older men. The mechanisms underlying the association between BP and mortality differ by levels of systolic BP. Cardiovascular deaths tended to be higher in the highest SBP group, and only noncardiovascular deaths were increased in the lowest SBP group. The latter finding suggests that low SBP may be not only an independent risk of mortality but also an indicator of a subclinical noncardiovascular comorbid condition. J Am Geriatr Soc 47:1415–1421, 1999.