Senile Dementia Of Alzheimer Type Research Articles

Management of cognitive determinants in senile dementia of Alzheimer's type: therapeutic potential of a novel polyherbal drug product.

The enigmatic etiology of neurodegenerative diseases poses a challenge for the development of novel and efficient drugs. The objective of the present study was to evaluate the efficacy of a polyherbal (test) formulation on cognitive functions, inflammatory markers and oxidative stress in healthy elderly as well as senile dementia of Alzheimer's type (SDAT) patients. A randomized double-blind placebo- and active-controlled clinical trial was performed in healthy elderly subjects and SDAT patients with an age range of 60-75 years. The polyherbal test formulation along with a placebo was given to healthy elderly subjects while the SDAT patients received either the test formulation containing extracts of Bacopa monnieri (whole plant), Hippophae rhamnoides (leaves and fruits) and Dioscorea bulbifera (bulbils) at a dose of 500 mg or donepezil drug (Aricept) at a dose of 10 mg, twice daily, for a period of 12 months. After every three months, cognitive functions were assessed by determining the mini mental state examination (MMSE) score, digital symbol substitution (DSS; subtest of the Wechsler Adult Intelligence Scale-Revised), immediate and delayed word recall (digital memory apparatus-Medicaid systems, Chandigarh, India), attention span (Attention Span Apparatus-Medicaid systems, Chandigarh, India), functional activity questionnaire (FAQ) and depression (geriatric depression scale) scores. Further inflammatory markers and level of oxidative stress were analyzed using standard biochemical tests. The trial was performed in 109 healthy subjects and 123 SDAT patients of whom 97 healthy subjects and 104 SDAT patients completed the study. Administration of the test formulation for a period of 12 months was effective in improving cognitive functions in the SDAT patients, when compared to the donepezil-treated group, as determined by the DSS (38.984 ± 3.016 vs 35.852 ± 4.906, P = 0.0001), word recall immediate (3.594 ± 1.003 vs 2.794 ± 0.593, P < 0.0001) and attention span (4.918 ± 1.239 vs 4.396 ± 0.913, P = 0.0208) scores. A significant improvement in the FAQ (11.873 ± 2.751 vs 9.801 ± 1.458, P < 0.0001) and depression (16.387 ± 2.116 vs 21.006 ± 2.778, P < 0.0001) scores was also observed, whereas no significant differences were observed in the MMSE and word recall delayed scores. The level of inflammation and oxidative stress was markedly reduced in the SDAT patients treated with the test formulation when compared to the donepezil-treated group indicating a likely mechanism of action of the test formulation (homocysteine 30.22 ± 3.87 vs 44.73 ± 7.11 nmol/L, P < 0.0001; C-reactive protein [CRP] 4.751 ± 1.149 vs 5.887 ± 1.049 mg/L, P < 0.0001; tumour necrosis factor alpha [TNF-α] 1139.45 ± 198.87 vs 1598.77 ± 298.52 pg/ml, P < 0.0001; superoxide dismutase [SOD] 1145.92 ± 228.75 vs 1296 ± 225.72 U/g Hb, P = 0.0013; glutathione peroxidase [GPx] 20.78 ± 3.14 vs 25.99 ± 4.11 U/g Hb, P < 0.0001; glutathione [GSH] 9.358 ± 2.139 vs 6.831 ± 1.139 U/g Hb, P < 0.0001; thiobarbituric acid reactive substances [TBARS] 131.62 ± 29.68 vs 176.40 ± 68.11 nmol/g Hb, P < 0.0001). Similarly, when healthy elderly subjects treated with the test formulation for 12 months were compared to the placebo group, a significant (P < 0.001) improvement in cognitive measures (MMSE, DSS, word recall delayed but not immediate, attention span, FAQ and depression scores) and a reduction in inflammation (reduction in homocysteine, CRP, IL-6 and TNF-α levels) and oxidative stress levels (reduction in SOD, GPx and TBARS and increase in GSH) was observed. This indicated a protective effect of the test formulation in managing cognitive decline associated with the ageing process. The results of this study demonstrate the therapeutic potential of this novel polyherbal formulation for the management and treatment of SDAT.

Silk Protein, Sericin as a Cognitive Enhancer in Alzheimer’s Disease

Alzheimer’s disease (AD) a well-known neurodegenerative disorder characterized by formation of amyloid plaques and neurofibrillary tangles and by loss of neurons is the most common type of Dementia, also called as Senile Dementia of Alzheimer Type (SDAT) which frequently occurs in elder people. Globally it was noticed that every year 3, 60, 000 new cases were admitted with severe AD. AD was first described by a German Psychiatrist and Neuropathologist, Dr. Alois Alzheimer in 1906 and was named after him. According to Cholinergic hypothesis, AD is caused by reduced synthesis of the neurotransmitter ACh, where in the AChE levels were increased which causes damage to the cholinergic neurons finally leading to cognitive impairments. At present, AChE inhibitors, Anti- amyloid vaccine and Vitamin E are recommended to treat AD but long-term exposure to these drugs causes side effects. Since treatment of AD with single drug is not a realistic option due to it’s the complicated nature, combination therapy of AChE inhibitor along with Antioxidants is felt necessary to treat Alzheimer’s disease effectively. Therefore, it is worthwhile to identify new and selective AChE inhibitors with an Antioxidant nature from natural source. Hence, in the present investigation, the natural bioproduct of silk viz. the Silk Protein, Sericin, having several beneficial qualities viz., Anti-bacterial, Antioxidant, Wound healing, Anti-tumor activity etc. has been chosen to evaluate its potential as “Cognitive enhancer”, AD-induced rat model by conducting experiments on Morphometric changes along with Learning and Memory efficiency; on Cholinergic system, Antioxidant system and Histological aspects in selected brain regions of control and experimental rats. The results in the present study on the Cholinergic system revealed that while ACh content was significantly elevated, AChE level was inhibited in all selected brain regions of rats treated with As a corollary to these biochemical aspects, the Histological Studies in control and different groups of experimental rat brain demonstrated that Sericin could effectively reverse the AD-induced damage in neurons of CC and HC regions, the centres for most of the cognitive functions. From all these findings, it was finally concluded that, Sericin can be used as a potential cognitive enhancer in general and Alzheimer’s disease in particular.

Prevention of age-associated neurodegeneration and promotion of healthy brain ageing in female Wistar rats by long term use of bacosides

Bacopa monnieri (L.), popularly known as Brahmi, is a revered Ayurvedic medicinal plant used as nerve tonic since time immemorial. The present study aims to investigate the neuroprotective effect of bacosides, the active saponins of Bacopa monnieri (L.) against age associated neurodegeneration and its impact over the prevention of Senile Dementia of Alzheimer's Type (SDAT). The optimum dose of bacosides with no adverse effect was selected by screening its dose dependant activity on ageing biomarker lipofuscin and SDAT biomarker neurotransmitter acetylcholine in the aged female Wistar rat brain. The selected therapeutic dose of bacosides (200 mg/kg) was orally administered for 3 months in middle aged and aged rats and further investigated for its protective action against age associated alterations in neurotransmission system, behavioral paradigms, hippocampal neuronal loss and oxidative stress markers. The results of the present study suggest that bacosides may act as a potential therapeutic intervention in forestalling the deleterious effects of ageing and preventing the age associated pathologies like SDAT.

頬部扁平上皮癌をMohs chemosurgeryで治療したアルツハイマー型認知症の1症例

An 89-year-old woman was given a diagnosis of senile dementia of Alzheimer type around 2003. In 2006, the patient was examined at a dermatology clinic complaining of tumor in the right buccal region. At the time, possible squamous carcinoma was pointed, but nothing was done for it. In March 2008, home care became difficult due to progression of dementia, and the patient was admitted to our hospital. On admission, a protruding skin tumor (20 x 20 x 2 mm, cauliflower-like surface) was observed in the right buccal region. Surgical ablation was recommended, however, the family strongly requested to let it follow its in natural course. In December 2008, the tumor increased rapidly to 40 x 55 x 25 mm with bleeding and a bad smell, which decreased her QOL markedly. After obtaining consent from the patient and her family, Mohs chemosurgery was performed. As the result, the tumor resolved and the QOL improved. Mohs chemosurgery is considered as a very effective treatments for rapidly advancing progressive skin cancer in patients with severe cognitive impairment.

Demonstration of aluminum in amyloid fibers in the cores of senile plaques in the brains of patients with Alzheimer’s disease

Aluminum (Al) exposure has been reported to be a risk factor for Alzheimer's disease (senile dementia of Alzheimer type), although the role of Al in the etiology of Alzheimer's disease remains controversial. We examined the presence of Al in the Alzheimer's brain using energy-dispersive X-ray spectroscopy combined with transmission electron microscopy (TEM-EDX). TEM-EDX analysis allows simultaneous imaging of subcellular structures with high spatial resolution and analysis of small quantities of elements contained in the same subcellular structures. We identified senile plaques by observation using TEM and detected Al in amyloid fibers in the cores of senile plaques located in the hippocampus and the temporal lobe by EDX. Phosphorus and calcium were also present in the amyloid fibers. No Al could be detected in the extracellular space in senile plaques or in the cytoplasm of nerve cells. In this study, we demonstrated colocalization of Al and beta-amyloid (Abeta) peptides in amyloid fibers in the cores of senile plaques. The results support the following possibilities in the brains of patients with Alzheimer's disease: Al could be involved in the aggregation of Abeta peptides to form toxic fibrils; Al might induce Abeta peptides into the beta-sheet structure; and Al might facilitate iron-mediated oxidative reactions, which cause severe damage to brain tissues.

What is ‘early onset dementia’?

There are two types of dementia with early onset: (i) presenile dementias; and (ii) senile dementias with early onset. Most patients who develop dementia before 65 years of age have Alzheimer's disease (AD). The remainder are likely to have vascular dementia (VaD), frontotemporal dementia, head injury, alcohol intoxication, or metabolic disorder. Presenile dementias, caused by frontotemporal lobar degeneration, progressive supranuclear palsy, and corticobasal degeneration, usually occur in patients of presenile and are rarely seen in patients of senile age. Although the factors responsible for the accelerated onset of the illness are not fully known, genetic abnormalities appear to be important in some types of presenile dementia, such as frontotemporal dementia with parkinsonism linked to chromosome 17. Conversely, senile dementias such as sporadic AD and VaD commonly occur in patients of senile age. These disorders may also occur in patients of presenile age, although less frequently. Alzheimer's disease was originally classified as a 'presenile dementia'. Since the 1980s, 'senile dementia of Alzheimer type' (SDAT) and 'Alzheimer's disease' have been considered to belong to the same pathological entity and both are now known as 'dementia of Alzheimer's type (DAT)' or merely 'Alzheimer's disease'. Rapid progression of cognitive impairment with neuropsychological syndromes and neurological symptoms has been considered a characteristic of early onset AD. However, recently, neurological symptoms such as spastic paraparesis, seizures, and myoclonic convulsions have been reported to occur infrequently in early onset AD, although language problems and visuospatial dysfunctions are common. There are at least three dominant genes that have been identified in cases of familial Alzheimer's disease with early onset, namely the amyloid precursor gene (APP), and the genes encoding presenilin 1 (PSEN1) and presenilin 2 (PSEN2). Therefore, genetic abnormalities are important factors contributing to the earlier onset of the illness. It is also important to investigate the pathophysiological mechanism in relation to genetic abnormalities, environmental factors, physical illnesses, and metabolic disturbances to understand the processes underlying the development of dementia with early onset.

Homovanillic acid and 5-hydroxyindoleacetic acid levels in cerebrospinal fluid of patients with senile dementia of Alzheimer type.

The possibility of disturbed dopamine and serotonin metabolism in senile dementia of Alzheimer type was studied. The basal concentrations of homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid (CSF) were studied in 28 patients with senile dementia of Alzheimer type and in 13 controls of similar age with no neurological disease. The concentrations of HVA were significantly reduced in the dementia patients compared to the concentrations of the controls. The values of HVA were also significantly reduced in the most severely demented patients compared to the less severely demented ones. There was a slight but statistically significant decrease in the 5-HIAA levels in the dementia patients compared to the levels of the controls. The 5-HIAA levels were reduced in the most severely demented patients compared to the controls but not when compared with the less severely demented patients. It is concluded that in severe forms of senile dementia of Alzheimer type, there is a decrease in the levels of HVA and 5-HIAA in CSF which may reflect a decreased turnover of dopamine and serotonin. Patients diagnosed as senile dementia of Alzheimer type, but with less severe symptoms, had levels of HVA and 5-HIAA similar to controls.

Vitamin B12 in CSF: reduced CSF/serum B12 ratio in demented men.

Vitamin B12 concentrations were determined in serum and cerebrospinal fluid (CSF) of 32 controls and 102 patients with dementia. The dementias were classified as Alzheimer's disease (AD), senile dementia of Alzheimer type (SDAT) and multi-infarct dementia (MID). A substantial number of patients (n = 42) could not be assigned to any of these diagnostic groups, as their dementias were of non-AD/SDAT and non-MID types. They were instead assigned to a group called non ultra descriptum (NUD). CSF B12 correlated significantly with serum B12. There were no statistically significant differences in serum B12 levels between the groups. Although with considerable overlap, CSF B12 concentrations and CSF/serum B12 ratios were significantly lower in the NUD group than in the control group. The NUD group had significantly lower CSF/serum B12 ratios than the group of patients with AD/SDAT. There was significant male predominance in the group of demented patients that had low CSF/serum B12 ratios outside the bivariate reference region. CSF and serum B12 levels appear insufficient as measures of the true brain vitamin B12 status. It may be a more dynamic approach to use the CSF/serum B12 ratio as an indication of transport function across the blood brain barrier, and possibly also across the CSF brain cell barrier.

EEG AND COMPUTED TOMOGRAPHY IN THE INVESTIGATION OF PATIENTS WITH SENILE DEMENTIA:

Fifty-six patients with senile dementia of Alzheimer type and 84 normal elderly people were examined by EEG and computed tomography. In discriminant function analysis of the computed tomography indexes the highest discriminant function coefficient was for width of the third ventricle. Using computed tomography, the groups were correctly classified for 84% of the subjects. In discriminant function analysis of the EEG variables the highest discriminant function coefficient was for dominant occipital rhythm; the groups were correctly classified for 86% of the subjects. In discriminant function analysis of the width of the third ventricle, an index of cortical atrophy, the dominant occipital rhythm, age and sex, the width of the third ventricle had the highest discriminant function coefficient; the groups were correctly classified for 90% of the subjects.

Acetylcholinesterase activities in cerebrospinal fluid of patients with senile dementia of Alzheimer type.

We have studied, as a possible marker of cholinergic neurons, the acetylcholinesterase (AChE) activity in cerebrospinal fluid (CSF) of 21 SDA patients and 9 controls of similar age with no neurological disease. The AChE activities were significantly lower in the SDA patients compared to the controls. The AChE activities were also lowered in the most severely demented patients compared to those who were less severely demented but the difference was not statistically significant. As a potential glia marker, beta-glucuronidase activity in CSF was studied, but no significant difference was found in the activities of the SDA patients compared to the controls. The reduced AChE activities in the CSF of the SDA patients may be related to the loss of cholinergic neurons or disturbed cholinergic metabolism in the brain.

Interaction between β-amyloid protein and heparan sulfate proteoglycans from the cerebral capillary basement membrane in Alzheimer’s disease

Proteoglycans are important in the pathogenesis of senile dementia of Alzheimer type (SDAT) by participating in amyloidogenesis. Knowledge about specific proteoglycan subtypes in SDAT may be of therapeutic advantage. In this study, we examined proteoglycan constituents of SDAT brains with reference to hyaluronic acid, heparan sulfate (HS), dermatan sulfate and chondroitin sulfate subtypes. Total proteoglycans showed a 1.6-fold increase in the hippocampus and 4.3-fold increase in the gyrus frontalis superior compared to non-demented elderly subjects. The HS subtype showed a 9.3-fold increase in hippocampus and a 6.6-fold increase in gyrus frontalis superior. Immunohistochemical studies of senile plaques revealed the expression of heparan sulfate proteoglycan (HSPG) in a portion of the core of typical plaques. β-amyloid expression was positive in senile plaques and the degenerated neuronal processes and capillary basement membrane, but was negative in endothelial cells. Microglial cells adjacent to senile plaques were positive for HLA-DR expression, and astroglial cells positive for glial fibrillary acidic protein were scattered around the microglial cells. Immunoelectron microscopic examination showed an electron-dense reaction for HSPG in the thickened basement membrane adjacent to the endothelial cells of capillary vessels, but not inside the endothelial cells. These findings suggest that a markedly increased HSPG in SDAT brains is most likely caused by HSPG from the blood capillary basement membrane and that the degenerated processes around senile plaques may arise from microglial or astroglial cells.

The venous manifestations of pulse wave encephalopathy: windkessel dysfunction in normal aging and senile dementia

Cerebral arterial, venous and cerebrospinal fluid (CSF) pulsations are closely coupled and this produces pulsation dampening or the windkessel effect. Normal pressure hydrocephalus is a manifestation of the breakdown of this windkessel effect with altered CSF and venous pulsations being noted. The aim of this study was to show that dysfunction of the windkessel mechanism is also a component of normal aging and senile dementia. The study group comprised 24 patients classified as either early senile dementia of Alzheimer's type (SDAT) or vascular dementia (VaD). The patients with dementia were compared with 12 age-matched non-cognitively impaired subjects, and 12 normal young individuals were compared with the normal aging group. MRI flow quantification was used to measure the nonpulsatile and pulsatile components of blood flow as well as the pulsation at the tentorial incisura. With normal aging blood flow decreased but arterial pulsations increased in volume by 49% (P=0.003). The CSF vented via the tentorial incisura does not change significantly with age and therefore increased venous pulsation is necessary. In patients with VaD the arterial pulse volume was higher by 24% and the straight sinus pulsation was higher by 57% than in normal aging subjects (P=0.05 and P=0.03, respectively). In patients with SDAT the total venous pulsation volumes were similar to those in normal aging subjects but there was less basal sinus pulsation. Normal aging, SDAT and VaD are associated with alterations in venous pulsation due to a breakdown of the windkessel effect.

Effect of kihito extract granules on cognitive function in patients with Alzheimer's‐type dementia

Background: It has been recently suggested that Japanese herbal (kampo) medicines, such as kami‐untan‐to, may improve cognitive function in elderly subjects with Alzheimer's disease. Polygalae radix is thought to be a useful component of kami‐untan‐to because it enhances the activity of choline acetyltransferase in cultured neuronal cells. The purpose of the present study was to investigate the safety and usefulness of kihito extract granules, a commercially available Japanese herbal medicine that contains P. radix, for elderly patients with senile dementia.Methods: Seventy‐five elderly subjects (84.4 ± 6.4 years) with senile dementia of Alzheimer type according to Diagnostic and Statistical Manual of Mental Disorders, 4th edition criteria were randomly assigned to the non‐treatment, goshajinkigan (control kampo medicine) or kihito groups. Each medicine was given three times a day for 3 months.Results: There was no severe adverse event in any of the groups. We examined the Mini‐Mental State Examination (MMSE), the activities of daily living (ADL) scale and cerebrovascular single photon emission computed tomography (SPECT) before and after treatment. MMSE scores were significantly improved only in the kihito group (+1.65 ± 0.53) but not in the non‐treatment (−0.3 ± 0.67) and goshajinkigan (−0.58 ± 0.49) groups. ADL scores remained unchanged in all groups. Treatment with kihito was not associated with an increase in cerebral blood flow.Conclusion: These results propose that kihito may be useful and has potential to be tested as a medicine for Alzheimer's‐type senile dementia, although further examination is required to clarify the mechanism of the improving effect of kihito on cognitive function.

Could Serum Antibody to Poly(ADP‐Ribose) and/or Histone H1 Be Marker for Senile Dementia of Alzheimer Type?

Poly(ADP-ribosyl)ation has been focused on ischemic injury in the brain in relation to Alzheimer's disease (AD). We have measured IgG antibodies against poly adenosine diphosphate-ribose (pADPR) as well as histone H1 (H1) in 26 patients with either AD or with senile dementia of Alzheimer type (SDAT), and found that 80.7% (21/26) were positive for anti-pADPR IgG antibodies. Anti-H1 IgG antibodies were less positive (57.6%) (15/26) than anti-pADPR IgG antibodies, however, titers of both antibodies were well correlated (r = 0.768). Meanwhile, similar studies on 32 patients with systemic lupus erythematosus (SLE) who were positive for anti-pADPR antibody showed poor correlation (r = 0.184) and the difference in the correlation was statistically significant (r < 0.01). It is worthy of remark that anti-double-stranded (ds) DNA antibody, which is the hallmark of SLE, was negative in all dementia patients. Together with the findings that major subclass in dementia is both IgG1 and IgG2 and that in SLE was IgG2, the mode of production of anti-pADPR antibody in AD and SDAT is under different regulation mechanisms from that in SLE. Given the evidence that major target for ADP-ribosylation is H1 molecule, the association between anti-pADPR and anti-H1 in AD/SDAT makes sense and supports the concept that modification of proteins renders them immunogenic. Whatever the regulation is, parallel assay of two antibodies above would be of use not only for monitoring the disease process but also as a prodrome for possible subsets of SDAT and AD.

Prescribing practice with cognition enhancers in outpatient care: are there differences regarding type of dementia?--Results of a representative survey in lower Saxony, Germany.

Previous studies of cognition enhancers have mainly focused on insufficiently defined groups of cognition disorders, e.g., "cerebral insufficiency". With regard to the various biological changes in senile dementia of Alzheimer's type (SDAT) and in vascular dementia (VD), which together make up the great majority of senile dementias, many authors have encouraged different studies of these types of dementias, especially since both can be diagnosed clinically with satisfying certainty. Since primary care physicians treat the majority of elderly and demented patients, they have their own experience with cognition enhancers. We were therefore interested to know, how far these physicians differ in their treatment of SDAT and VD. We performed a representative survey (response rate 83.2%; 145 family physicians and 14 neuropsychiatrists) in the Goettingen area. A written case vignette described a 70-year-old widow with moderate dementia and vascular risk factors which are easily treated with drugs. Two versions were randomly assigned, in which (version A) either a "typical" VD history or a typical SDAT history (version B) were described. After perusal, the physician was asked whether and which drugs he would choose to treat the cognitive disorders in this patient. Most frequently, piracetam (A/B: 25.6%/30.9%), ginkgo biloba (24.4%/28.4%), and nimodipine (14.1%/25.9%) were considered. Aspirin was cited by 29.5%(A) and 17.3%(B) of the physicians respectively. As far as the type of dementia was concerned, significant differences were found only for co-dergocrine, which was preferred in SDAT. The following inter-group trends were observed: family physicians considered ginkgo biloba more often than nimodipine or co-dergocrine. The results show the apparent importance of cost-and safety aspects, while the type of dementia has hardly any impact. The latter impression corresponds to the results of drug trials demonstrating no different efficacy. In our opinion, aspirin was not sufficiently taken into consideration.

Educational Level as a Modulator of Cognitive Performance and Neuropsychyatric Features in Parkinson Disease

To test a possible association between the educational level (EL), cognitive performance, and neuropsychiatric features in Parkinson disease (PD). An inverse association has been reported between EL and cognitive dysfunction in patients with senile dementia of Alzheimer type but it is yet unsettled whether education has a similar effect on cognition in PD. Seventy-two PD patients (45 males, mean age 68.7+/-11.6 y) underwent a detailed neurologic examination, a battery of neuropsychologic tests, and questionnaires for the evaluation of psychosis, sleep disturbances, and depression. According to the number of educational years, patients were divided into 3 groups: low EL (0 to 8 y), (15 patients), intermediate EL (9 to 12 y) (28 patients), and high EL (>/=13 y) (29 patients). Patients with a higher EL had a better cognitive function and an association was found between the patients' EL and their scores in various neuropsychologic tests mainly those sensitive to frontal lobe dysfunction. Low education was associated with an increased risk for hallucinations and a trend for more depression, delusions, and sleep disturbances. The association between high educational attainment and the lower risk of cognitive dysfunction suggest that education might modulate cognitive performance in PD.

日本語版Ｄｅｍｅｎｔｉａ Ｑｕａｌｉｔｙ ｏｆ Ｌｉｆｅ Ｉｎｓｔｒｕｍｅｎｔ（ＤＱｏＬ‐Ｊａｐａｎｅｓｅ Ｖｅｒｓｉｏｎ）を用いた認知症高齢者の主観的Ｑｕａｌｉｔｙ ｏｆ Ｌｉｆｅに関する縦断評価

There are few longitudinal studies on the subjective quality of life for elderly persons living in their own homes. The purpose of this study was to clarify the validity and reliability of the Japanese version of the Dementia Quality of Life Scale (JDQoL) used in a follow-up survey as part of a longitudinal study in Japan. A baseline study was conducted from November 2002 to January 2003, and a year later a follow-up study was conducted from October 2003 to January 2004. The subjects included 72 (19 men and 53 women) elderly persons with dementia living in their own homes. Sixty-six were diagnosed with vascular dementia (VD) and 6 had senile dementia of Alzheimer's type (SDAT). The follow-up study included 60 subjects (VD: 56 and SDAT: 4); _10 of the original subjects were hospitalized, one died, and one was unable to attend daycare because of deterioration. Evaluation was conducted using the JDQoL, MiniMental State Examination (MMSE), and Geriatric Depression Scale (GDS). For the MMSE, the average score of the subjects in the follow-up study was 20.87 (+/- 4.80), which was significantly higher than the score of subjects that were excluded from the follow-up study (17.82 +/- 5.65). At baseline, reliability coefficient was demonstrated by Cronbach's alpha value of 0.744 approximately 0.886. One year later, Cronbach's alpha was 0.723 approximately 0.872. Among the subjects in the follow-up study, MMSE scores decreased significantly compared with the baseline study. In the subscales of the JDQoL, Negative Feelings (reversal item) significantly improved and Feeling of Belonging significantly decreased after one year (p<0.05). Each subscale of the JDQoL had significant correlation with the GDS at baseline and follow-up. Scores on the GDS at baseline had significant correlation with Self Esteem, Positive Feelings, Negative Feelings, and Feeling of Belonging of the JDQoL at follow-up (0.320 to 0.504; p<0.05). We demonstrated that the reliability and validity of the JDQoL was comparable to the English version of DQoL. Subjective QOL did not decline for all sub-scales, Negative Feelings in the JDQoL significantly improved compared to baseline.

Methanesulfonyl fluoride, an acetylcholinesterase inhibitor, attenuates simple learning and memory deficits in ischemic rats

Methanesulfonyl fluoride (MSF), a highly selective CNS inhibitor of acetylcholinesterase, has been recently demonstrated to promote improvement in cognitive performance in patients with senile dementia of Alzheimer type. Because a similar cognitive impairment may accompany stroke, we investigated in the present study whether treatment with MSF could produce beneficial effects in adult rats subjected to an experimental stroke model. Sprague–Dawley rats received transient 60 min intraluminal occlusion of the right middle cerebral artery (MCAo) and were given i.p. injections of either MSF (1 mg/kg at 24 and 48 h post-MCAo and 0.3 mg/kg thereafter every other day) or the vehicle, peanut oil, for 4 weeks. Behavioral tests and biochemical assays were performed at 28 days post-surgery. MSF treatment produced about 90% inhibition of acetylcholinesterase in the brain. Ischemic animals that received the vehicle displayed significant elevated body swing biased activity (84.8 ± 10%) and significantly prolonged acquisition (398 ± 62 s) and shortened retention (79 ± 26 s) of the passive avoidance task. Interestingly, while the ischemic animals that received the MSF exhibited elevated body swing biased activity (87.7 ± 8%), they performed significantly better in the passive avoidance task (255 ± 36 s and 145 ± 18 s in acquisition and retention) than the vehicle-treated animals. Moreover, whereas brains from both groups of animals revealed similar extent and degree of cerebral infarction, the MSF-treated ischemic animals showed more intense immunoreactivity, as well as a significantly higher number (10–15% increase) of septal choline acetyltransferase-positive cells than the vehicle-treated ischemic animals. These results show that MSF, possibly by preserving a functional cholinergic system, attenuated stroke-induced deficits in a simple learning and memory task.

日本語版Ｄｅｍｅｎｔｉａ Ｑｕａｌｉｔｙ ｏｆ Ｌｉｆｅ Ｉｎｓｔｒｕｍｅｎｔの作成と信頼性・妥当性の検討

The aim of this study was to develop the Dementia Quality of Life Instrument-Japanese version (DQoL-Japanese Version). The subjects were 72 elderly patients, 19 men and 53 women (Vascular Dementia: 66, Senile dementia Alzheimer type 6) using day care and day services who had obtained approval for participation in the investigation. The interview survey was conducted from October 2002 to January 2003. In the subscales of the DQoL-Japanese Version, "negative feelings" scored the highest and "affirmative feelings" the lowest. There was a significant correlation coefficient between the test and those of a conducted 2 weeks later, ranging from 0.730 to 0.857 (p<0.05). The internal consistency reliability for the five scales ranges from alpha=0.66 to 0.864. There was a significant correlation coefficient between the Geriatric Depression Scale (GDS) and DQOL sub-scales such as "self esteem," "positive affect", "negative feelings" and "feeling of belonging". On the other hand, there was no significant relationship between the GDS and "aesthetics" of the DQoL-Japanese Version. It was suggested that the DQoL-Japanese Version DQoL is useful to measure subjective QOL of elderly patients with dementia. The subjects who understood the questions of the DQoL-Japanese Version and were able to be interviewed, had a Mini-Mental State score of 13 points or more. It was clarified that DQoL-Japanese Version was reliable and showed evidence of validity as well as the original DQOL.

Quetiapine Treatment for Behavioral and Psychological Symptoms in Patients with Senile Dementia of Alzheimer Type

The purpose of this study was to assess the effect of quetiapine in the treatment of behavioral and psychological symptoms of dementia (BPSD) in patients with senile dementia of Alzheimer type (SDAT). Sixteen SDAT patients with BPSD were recruited and quetiapine (25– 200 mg/day) was prescribed for 8 weeks. BPSD were evaluated with the Behavioral Pathology in Alzheimer’s Disease Rating Scale (BEHAVE-AD) and Cohen-Mansfield Agitation Inventory (CMAI) at week 0 (baseline) and week 8 (endpoint). The severity of the extrapyramidal symptoms was also assessed by the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) at baseline and endpoint. Significant improvements were seen in the CMAI total score and in the BEHAVE-AD subscales of delusions, activity disturbances, aggressiveness, diurnal rhythm disturbances and in the BEHAVE-AD overall severity. There was no significant difference between the baseline and endpoint in the DIEPSS score. These data indicate that quetiapine is effective in controlling BPSD with favorable adverse-event profiles.