Intellectual faculties in patients with Alzheimer's disease regress to the level of a 4–5-year-old child

Background:   The present study investigated when children acquire the cognitive abilities and daily living skills that are lost in Alzheimer's disease.
Methods:   Among a total of 1046 students in kindergarten and elementary schools affiliated with Gunma University, Japan, five female and five male students in each grade were selected at random and examined by the mini-mental state examination (MMSE) and physical self-maintenance scale (PSMS). For comparison, a total of 135 outpatients with Alzheimer's disease were examined. The results of MMSE and PSMS from the first visit to Gunma University Hospital after the onset of Alzheimer's disease were used.
Results:   The MMSE score gradually increased from 10 points in the 1st year of kindergarten (age 3 in Japan) to 29 points in the 6th grade of elementary school (age 11 in Japan). The PSMS score increased similarly from 3 points in the 1st year of kindergarten to 6 points in the 6th grade of elementary school. The mean scores of MMSE and PSMS were 17.3 and 3.7 in the Alzheimer patients' group. These findings suggested that cognitive and daily performance abilities examined by MMSE and PSMS are acquired in childhood during kindergarten and the early grades of elementary school.
Conclusion:   These cognitive and daily performance abilities of Alzheimer's disease outpatients regress to a level of a child between 4 and 5 years old. This simple understanding of Alzheimer's disease patients may contribute to further appropriate care by non-specialists and caregivers.     

Longitudinal patterns of unawareness of memory deficits in mild Alzheimer's disease

Aim:   Patients with Alzheimer's disease (AD) frequently demonstrate impaired awareness of their cognitive difficulties. However, less is known about the longitudinal progression of this phenomenon. We examined the longitudinal evolution of unawareness in patients with mild AD to determine whether impaired awareness progresses with cognitive decline.
Methods:   Based on Mini-Mental State Examination (MMSE) score changes after a 1-year follow up, 39 patients were regarded as the stabilized group and 19 patients were regarded as the non-stabilized group. The unawareness of memory impairment was evaluated with a standardized questionnaire system based on the Everyday Memory Checklist (EMC). The EMC scores for the patient's own rating, the caregivers' rating and the unawareness score, defined as the difference between these (caregiver rating – patient rating), were analyzed.
Results:   Although unawareness scores were similar in the two groups at the initial examination, they were significantly higher in the non-stabilized group than in the stabilized group at the follow up examination. There was a significant and negative correlation between change in unawareness score and change in MMSE score over time ( r  = −0.56, P  < 0.0001).
Conclusion:   Our results indicated that impaired awareness progressed with cognitive decline. The EMC may be a simple and useful tool for the monitoring of progression in patients with AD.     

Vascular Care in Patients with Alzheimer's Disease with Cerebrovascular Lesions—A Randomized Clinical Trial

OBJECTIVES: To investigate whether vascular care slows dementia progression in patients with Alzheimer's disease with cerebrovascular lesions on neuroimaging.
DESIGN: Multicenter randomized controlled clinical trial with 2-year follow-up.
SETTING: Neurological and geriatric outpatient clinics in 10 Dutch hospitals: three academic, five teaching, and two midsize community hospitals.
PARTICIPANTS: One hundred thirty community-dwelling patients with mild dementia fulfilling clinical criteria for Alzheimer's disease with cerebrovascular lesions on neuroimaging.
INTERVENTION: Patients randomized to vascular care were treated according to strict guidelines for hypercholesterolemia and hypertension. Acetylsalicylic acid, folic acid, and pyridoxine were prescribed. During visits every 3 months special attention was paid to smoking cessation, losing weight, and stimulating physical exercise.
MEASUREMENTS: Primary outcome was disability, measured according to the Interview for Deterioration in Daily activities in Dementia (IDDD). Secondary outcomes were changes on the Mini-Mental State Examination (MMSE), the Revised Memory and Behavioural Problems Checklist (RMBPC), a composite measure of "poor outcome" (death, institutionalization, or severe clinical decline), and costs.
RESULTS: Patients in the vascular and standard care condition declined equally on the IDDD (13.7 vs 11.0 points; difference 2.7, 95% confidence interval =−3.1–8.6). There was no treatment effect on the MMSE or RMBPC. There were no differences in institutionalization rate, "poor outcome" (41.4% vs 35.4%, P =.50), or costs. In the intervention group, there were three intracerebral hemorrhages and one gastrointestinal hemorrhage, versus none in the control group.
CONCLUSION: Multicomponent vascular care, combining pharmacological and nonpharmacological interventions, does not slow decline in patients with Alzheimer's disease with cerebrovascular lesions.     

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.     

Arterial pulse wave velocity in elderly patients with dementia

Background:   Cardiovascular events influence the quality of life and mortality of elderly patients. Arterial stiffness measured by aortic pulse wave velocity is a useful means of predicting the presence of cardiovascular diseases, even in subjects over 70 years old. This procedure is non-invasive, but the usefulness and easiness of aortic pulse wave velocity for patients with dementia are still unclear. Therefore, to determine how useful and easy it is to measure aortic pulse wave velocity, we evaluated arterial stiffness in patients with or without dementia who required care and support for their daily life.
Methods:   Fifty-nine subjects over 70-years-old who suffered from dementia were enrolled in this study. After we excluded arteriosclerosis obliterans (ankle-brachial pressure index < 0.80; n =  10) by arterial pulse wave velocity, we classified these subjects into two groups: subjects with Alzheimer's disease ( n  = 25) and subjects with vascular dementia ( n  = 24) who were diagnosed by magnetic resource imaging and mini-mental state examination.
Results:   The authors of the present paper could easily and precisely evaluate arterial stiffness of all patients. The mean pulse wave velocity of right and left brachial-tibial arteries in subjects with Alzheimer's disease (1740 ± 385 cm/s) was significantly lower than those subjects with vascular dementia (2436 ± 586; P  < 0.001).
Conclusion:   The data included in the present study indicate that subjects with Alzheimer's disease had decreased arterial stiffness and would show a lower risk of cardiovascular diseases compared to subjects with other diseases including vascular dementia.     

Cognitive profiles and response to donepezil treatment in Alzheimer's disease patients

Background:   The aim of this study was to determine whether there are certain characteristic neuropsychological profiles, assessed by the Mini-Mental State Examination (MMSE) at baseline, which predict donepezil treatment response.
Methods:   A total of 112 consecutive outpatients with Alzheimer's disease (AD) were treated with donepezil for 3–4 months. Multiple regression analysis was performed to estimate the relative contributions of individual subscales at baseline to the MMSE change (study point – baseline). To identify the characteristic patterns in cognitive deficits of patients with AD who responded to donepezil therapy, the subscales of the MMSE at baseline of responders and non-responders were compared.
Results:   Multiple regression analysis revealed that lower scores on attention and calculation, and language function, and a higher scale on orientation (date) are related to an improvement of the MMSE. When an improvement of 4 or more points on the MMSE score was defined as a significant response, responders scored significantly lower than non-responders on attention and calculation, whereas non-responders scored significantly lower than responders on memory.
Conclusion:   Our results suggest that individual differences in patterns of neuropsychological impairments may partly contribute to the diversity of the response to donepezil treatment. Although further studies with more detailed neuropsychological tests are needed to confirm our results, the MMSE may add to the prediction of response to donepezil treatment in patients with AD.     

Caries prevalence in older persons with and without dementia

OBJECTIVES: To examine the prevalence of coronal and root caries in a memory clinic–based population of elderly patients with and without a diagnosis of dementia and to examine the influence of age, sex, social relations, social position, and functional ability.
DESIGN: Cross-sectional.
SETTING: Patients referred with possible cognitive dysfunction were recruited from two university hospital dementia clinics.
PARTICIPANTS: In total, 106 dentate persons participated in the study. Mean age was 82, 69 were women, and 87 had a diagnosis of dementia.
MEASUREMENTS: Data from interviews and a clinical examination were collected. The diagnosis of dementia was made at the dementia clinics according to the criteria of International Classification of Diseases, Tenth Revision . Active coronal and root caries was assessed using previously defined diagnostic criteria from the National Institute of Dental and Craniofacial Research.
RESULTS: The mean number of coronal and root surfaces with caries was statistically significantly higher in subjects with a diagnosis of dementia (7.0 vs 2.7, P <.05). Subjects with a diagnosis of Alzheimer's disease had a significantly higher mean number of root surfaces with caries (4.9, P <.05) than subjects with other dementia diagnoses (2.3) and those without dementia (1.7). People with Alzheimer's disease also had significantly more mean total caries than subjects without dementia (7.8 vs 2.7, P <.05). Participants with a Mini-Mental State Examination (MMSE) score less than 24 had significantly more caries than participants with a MMSE-score of 24 or higher (7.6 vs 4.3, P <.05).
CONCLUSION: Patients with newly diagnosed dementia already had a high level of active dental caries when they were referred to the memory clinic. The high caries prevalence was related to dementia type and severity.     

Influence of Antisocial and Psychopathic Traits on Decision-Making Biases in Alcoholics

Background:  Although decision-making processes have become a principal target of study among addiction researchers, few studies have specifically examined decision-making among individuals with alcohol dependence (AD) and findings to date are mixed. The present study examined the relationship between AD and decision-making, and tested whether different facets of antisocial and psychopathic traits explain this association.
Methods:  Participants were men with AD ( n  =   22), AD and comorbid antisocial personality disorder (AD + ASPD; n  =   17), or a history of recreational alcohol use, but no current or lifetime symptoms of a substance use disorder, conduct disorder, or ASPD ( n  =   21). Decision-making was tested using the Iowa Gambling Task (IGT).
Results:  Across groups, participants reported similar levels of awareness of the contingencies of the task, but the AD groups with and without ASPD had poorer IGT performance compared with controls ( p  < 0.05). A block-by-block analysis revealed that while AD had slow but steady improvement across the task, AD + ASPD exhibited initial improvement followed by a significant decrease in advantageous decision-making during the last 20 trials ( p  < 0.05). This was further confirmed via evidence that impulsive/antisocial personality traits but not psychopathic traits mediated poor IGT performance beyond ASPD diagnosis.
Conclusions:  Alcohol-dependent males favored risky choices regardless of whether they met criteria for ASPD. However, decision-making deficits were more pronounced among those with ASPD, and personality traits characterized by impulsive and antisocial tendencies mediated the relationship between AD and decision-making.     

Changes in cognitive functions of patients with dementia of the Alzheimer type following long-term administration of donepezil hydrochloride: Relating to changes attributable to differences in apolipoprotein E phenotype

Aim:   We conducted a study of changes in cognitive functions by long-term monitoring of dementia of Alzheimer type (DAT) patients to investigate the relationship between the progression of DAT symptoms and the presence of apolipoprotein (ApoE)4.
Methods:   The subjects consisted of 40 DAT patients who had been treated with donepezil for 3 years or more. The Mini-Mental State Examination (MMSE) and Alzheimer's Disease Assessment Scale – Cognitive Subscale Japanese version (ADAS-Jcog), were conducted annually. The patients were categorized into ApoE4⁺ and ApoE4^- groups. Changes in initial cognitive function assessment score (0 years) were then studied longitudinally at each stage of the observation period (1, 2, 3 years) (Wilcoxon's signed-rank test). Moreover, the scores at each time period were compared cross-sectionally between the two groups (Mann–Whitney U -test).
Results:   Significant decreases in MMSE scores were observed at the three time periods in both groups ( P  < 0.01) in the cross-sectional study. In the longitudinal study, the ApoE4⁺ group demonstrated a lower trend ( P  < 0.1) after 1 year only. Significantly poorer ADAS-Jcog scores were observed in the ApoE4⁺ group at the 3-year point both in the longitudinal and in the cross-sectional study ( P  < 0.05). For ADAS-Jcog sub-items, in the longitudinal study, orientation was demonstrated to be significantly poorer in the ApoE4⁺ group in the third year ( P  < 0.05).
Conclusion:   ApoE4 was suggested to not only be a risk factor for disease onset, but also a risk factor for exacerbation of symptoms with respect to long-term prognosis.     

Binswanger病与Alzheimer病脑电地形图对比研究

本文对照观察了Ｂｉｎｓｗａｎｇｅｒ病（ＢＤ）和Ａｌｚｈｅｉｍｅｒ病（ＡＤ）各３０例患者脑电地形图的变化。结果发现，ＢＤ患者局灶性和阵发性脑电改变的阳性率明显高于ＡＤ患者，并且双侧脑电功率谱不对称，以额、中央、枕区θ波多见，而ＡＤ患者双侧功率谙基本对称，以额、颞、顶区δ波多见。ＢＤ患者智能障碍程度与脑电异常改变有显著相关性，提示脑电地形图检查对ＢＤ和ＡＤ的鉴别诊断有参考价值。     

Effect of Fish Oil Supplementation on Quality of Life in a General Population of Older Dutch Subjects: A Randomized, Double-Blind, Placebo-Controlled Trial

OBJECTIVES: To investigate the effect of eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) supplementation on quality of life (QOL).
DESIGN: Randomized, double-blind, placebo-controlled trial.
SETTING: Independently living individuals from the general older Dutch population.
PARTICIPANTS: Three hundred two individuals aged 65 and older without depression or dementia.
INTERVENTION: 1,800 mg/d EPA-DHA (n=96), 400 mg/d EPA-DHA (n=100), or placebo capsules (n=106) for 26 weeks.
MEASUREMENTS: QOL was assessed using the short version of the World Health Organization QOL questionnaire (WHOQOL-BREF). The WHOQOL-BREF covers four domains: physical health, psychological health, social relationships, and satisfaction with environment. The total score range is 26 to 130, with higher scores indicating a more favorable condition.
RESULTS: Mean age of the participants was 70, and 55% were male. Plasma concentrations of EPA-DHA increased 238% in the high-dose and 51% in the low-dose EPA-DHA group, reflecting excellent adherence. Median baseline total WHOQOL scores ranged from 107 to 110 in the three groups and were not significantly different from each other. After 26 weeks, the mean difference from placebo was −1.42 (95% confidence interval (CI)=−3.40–0.57) for the high-dose and 0.02 (95% CI=−1.95–1.99) for the low-dose fish oil group. Treatment with 1,800 mg or 400 mg EPA-DHA did not affect total QOL or any of the separate domains after 13 or 26 weeks of intervention.
CONCLUSION: Supplementation with high or low doses of fish oil for 26 weeks did not influence the QOL of healthy older individuals.     

Results from two randomized clinical trials evaluating the impact of quarterly recovery management checkups with adult chronic substance users

Aims   Post-discharge monitoring and early reintervention have become standard practice when managing numerous chronic conditions. These two experiments tested the effectiveness of recovery management checkup (RMC) protocols for adult chronic substance users.
Intervention   RMC included quarterly monitoring; motivational interviewing to provide personalized feedback and to resolve ambivalence about substance use; treatment linkage, engagement and retention protocols to increase the amount of treatment received.
Participants and setting   Recruited from sequential addiction treatment admissions, participants in the two experiments were, on average, 36 and 38 years of age, mainly female (59% versus 46%), African American (85% versus 80%) and met past-year criteria for dependence (87% versus 76%).
Design   Participants in both experiments were assigned randomly to the RMC or control condition and interviewed quarterly for 2 years.
Measurement   The Global Appraisal of Individual Needs (GAIN) was the main assessment instrument.
Findings   RMC participant outcomes were better than control participants in both experiments. Effect sizes were larger in the second experiment in terms of reducing days to readmission (Cohen's d  = 0.41 versus d  = 0.22), successive quarters in the community using substances ( d  = −0.32 versus −0.19), past-month symptoms of abuse/dependence ( d  = −0.23 versus −0.02) and increasing the days of abstinence over 2 years ( d  = +0.29 versus 0.04).
Conclusion   RMC, which provided ongoing monitoring and linkage, is feasible to conduct and is effective for adults with chronic substance dependence.     

Association between a promoter polymorphism of the paraoxonase PON1 gene and pathologically verified idiopathic Parkinson's disease

Background:  Exposure to pesticide is associated with an elevated risk of Parkinson's disease (PD). Oxidative stress is also implicated in the etiology of PD. Paraoxonase (PON1) detoxifies organophosphates and exhibits antioxidant properties. It was postulated that polymorphisms of the PON1 gene lead to increased risk of PD.
Methods:  The seven polymorphisms of the PON1 gene were typed and neuropathologic examination performed in 360 Japanese people (191 men and 169 women) consecutively autopsied at a general hospital.
Results:  Thirty-three patients (18 men and 15 women) were diagnosed with pathologically verified idiopathic PD (pviPD). The proportion of male patients with pviPD was highest in the AA genotype (29.4%) of the G(−824)A polymorphism, followed by the GA genotype (9.3%), and least in the GG genotype (6.0%). These genotypic distributions and allele frequency were significantly different between male patients with and without pviPD ( P  = 0.021 and P  = 0.012, respectively). The odds ratio for the −824 A allele versus the −824G allele was 2.47 (95% CI 1.23–4.96). No association between pviPD and the PON1 polymorphisms was found in the female patients.
Conclusion:  Possession of the −824A allele may increase the risk of PD in Japanese men.     

Waist circumference correlates with hepatic fat accumulation in male Japanese patients with non-alcoholic fatty liver disease, but not in females

Background and Aim:  Abdominal obesity, a component of metabolic syndrome, is a major risk factor for non-alcoholic fatty liver disease (NAFLD). In recent worldwide definitions of metabolic syndrome, waist measurement has been proposed as a simple and useful estimate of abdominal obesity, taking into account gender differences in waist circumference. The present cross-sectional study investigated the correlation of hepatic fat accumulation and waist circumference in Japanese NAFLD patients to determine if there are gender differences in this relationship.
Methods:  Consecutive patients ( n  = 2111) who had at least one of two criteria for liver disease (alanine aminotransferase [ALT] level >30 IU/mL and aspartate aminotransferase [AST]/ALT ratio <1) underwent abdominal ultrasonography. Patients positive for hepatitis B virus, hepatitis C virus or autoimmune antibodies and whose alcohol intake was >20 g/day were excluded. Patients with NAFLD underwent abdominal computed tomography. Hepatic fat accumulation was estimated by liver/spleen attenuation ratio (L/S ratio) and visceral adipose accumulation was measured as visceral fat area (VFA) at the umbilical level.
Results:  Of the 221 NAFLD patients, 103 were females. In males, the relationship between L/S ratio and waist circumference was negative ( r  =−0.356, P  < 0.01), and there was no correlation in the female group. The relationship between L/S ratio and VFA was negative in both groups (males: r  = −0.269, P  < 0.01; females: r  = −0.319, P  < 0.01). Subcutaneous fat area/total fat area ratio at the umbilical level was larger in females than in males ( P  < 0.01).
Conclusions:  In NAFLD patients, waist measurement is more susceptible to gender differences than VFA.     

Different changes of bone mineral density and nutritional status after hospitalization between vascular dementia and Alzheimer's disease in elderly female patients

Background:   Bone fractures strongly influence morbidity and mortality in elderly patients with dementia. The goal of this study was to examine whether difference in the type of dementia affects changes of bone mineral density (BMD) during hospitalization with rehabilitation programs.
Methods:   Ninety-four Japanese elderly female patients were enrolled. BMD, Mini-Mental State Examination (MMSE) scores, and levels of serum albumin, calcium-related factors and urinary calcium excretion were measured.
Results:   Multivariable analyses indicated that serum albumin levels and MMSE scores were positively correlated with changes in BMD after 2 years hospitalization. Significant reduction of BMD levels after hospitalization were observed in patients with severe dementia (MMSE scores, <10) or with severe malnutrition (serum albumin, <2.0). We next classified our subjects into three groups according to the 4th edn of the Diagnostic and Statistical Manual criteria: non-dementia (ND), Alzheimer's disease (AD) and vascular dementia (VaD). Although there were no significant differences in age and physical activities among the groups; the levels of BMD were maintained in AD as well as ND but not in VaD. Notably, calcium excretion levels were significantly decreased after hospitalization in AD as well as ND but not in VaD. Serum 25(OH)D levels were also restored in AD but not in VaD. In addition, the nutritional status significantly improved in AD but not in VaD.
Conclusion:   The levels of BMD were maintained and the nutritional status was improved in AD but not in VaD for 2 years hospitalization with rehabilitation programs. These results suggest that different programs including nutritional support may be necessary for maintaining BMD levels in VaD as compared with AD during hospitalization.     

A model for estimating cirrhosis in patients with type 1 autoimmune hepatitis

Aim:  Longstanding cirrhosis has been recognized as a risk factor for the development of hepatocellular carcinoma in patients with autoimmune hepatitis (AIH). Thus, the accurate determination of cirrhosis is important for prognostication, decisions regarding treatment and monitoring of disease progression. The aim of this study was to identify independent predictors of cirrhosis and to develop a model for estimating cirrhosis in patients with type 1 AIH.
Methods:  Using the training sample, consisting of 121 patients with type 1 AIH, we retrospectively examined independent predictors of cirrhosis and constructed a model for estimating cirrhosis. Validation was prospectively performed in the validation sample, consisting of 35 patients.
Results:  Using a stepwise multiple linear regression analysis, three predictors of serum immunoglobulin A level, ratio of aspartate aminotransferase to alanine aminotransferase, and platelet count were elicited, and a model for estimating cirrhosis was determined as follows: risk score = −0.113 + 0.0006056 × immunoglobulin A (mg/dL) + 0.155 × ratio of aspartate aminotransferase to alanine aminotransferase − 0.007079 × platelet (×10⁴/mm³). In the training sample, the sensitivity and specificity were 90% and 83%, respectively, when patients presenting a risk score ≥0.20 were estimated to be cirrhotic. When this model was applied to the validation sample, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 83%, 97%, 83%, 97% and 94%, respectively.
Conclusion:  It is suggested that this model could be useful for the estimation of cirrhosis in patients with type 1 autoimmune hepatitis.     

Outcome from surgical management of secretory pituitary adenomas in Christchurch,New Zealand

Abstract
Background:  Recent evidence has highlighted the importance of the neurosurgeon in the management of secretory pituitary tumours, but most reports are from major centres.
Aims:  To audit the surgical outcome of patients with acromegaly and Cushing's disease treated in a small centre (Christchurch, New Zealand) by a dedicated neurosurgeon with an interest in pituitary disease, and follow-up through an outpatient Department of Endocrinology.
Methods: All cases of acromegaly and Cushing's disease admitted for surgery in Christchurch Hospital between 1984 and 2000 were audited. Data concerning preoperative findings, surgical remission rate, complications and follow-up were obtained from 44 patients (28 acromegaly, 16 Cushing's disease).
Results: Of the 28 acromegalic patients, 14 patients (50%) had a mean growth hormone level <2.5 µg/L within the first postoperative week. Of the 15 Cushing's disease patients in whom the pituitary fossa was explored, 13 patients (87%) entered a postoperative remission, defined as an 08.00 h cortisol <200 nmol/L (normal range 250−800 nmol/L). No perioperative deaths occurred. Two of the 43 patients (4.7%) developed permanent diabetes insipidus, while eight of the 28 patients who were operated on for acromegaly (29%) eventually required some replacement treatment for hypopituitarism during follow-up (one presented with apoplexy and seven were treated with postoperative radiotherapy).
Conclusion: In a small centre with a dedicated pituitary surgeon, operative remission rates approach those obtained in larger, more specialized centres. However, given New Zealand's small, but geographically spread population, consideration should be given to establishing one or two units for the surgical management of secretory pituitary adenomas. (Intern Med J 2003; 33: 168−173)     

Volumetric and visual assessment of the mesial temporal structures in Alzheimer's disease

Background: Alzheimer's disease is the commonest cause of dementia. Clinical diagnosis of Alzheimer's disease may be difficult. Magnetic resonance imaging has a role to play in diagnosis.
Aim: To assess whether volumetric and/or visual assessment of the mesial temporal structures is useful in separating patients with Alzheimer's disease from age matched controls.
Methods: Twenty-four patients with Alzheimer's disease diagnosed by NINCDS/ADRDA criteria and 15 age matched controls were studied with magnetic resonance imaging (MRI) and volumetric techniques. Segmented volumes of the mesial temporal structures were assessed visually and volumetrically.
Results: Volumetric analysis demonstrated significant (p<.001) differences between the two groups, but showed overlap in individual cases. Discriminant function analysis predicted correct group membership (patient or control) in 85% of cases. Visual assessment alone demonstrated a sensitivity of 92% and a specificity of 93% in distinguishing the Alzheimer patients from controls.
Conclusion: Volumetric and visual assessment of the mesial temporal structures is useful in separating Alzheimer patients from controls. Overlap is present in individual cases. Visual assessment was as useful in separating the two groups as the volumetric analysis. (Aust NZ J Med 1994; 24: 547–553.)     

Long-term cognitive benefits of donepezil in Alzheimer's disease: A retrospective comparison between 1994–1999 and 2000–2004

Objective:   In order to address an issue of how long Alzheimer's disease (AD) patients should receive donepezil, we estimated long-term effect of donepezil on cognition as well as its influential factors. We also evaluated the additional effect of cerebrospinal fluid (CSF)-tau protein levels on diagnosis.
Methods:   We compared cognitive changes between current (2000–2004) AD patients (donepezil users) and previous AD patients, seen by us 1994–1999, without receiving donepezil (non-donepezil users) by a mixed effect model. Cognition was assessed by Mini-Mental State Examination (MMSE) at 6-month intervals up to 24 months. Sensitivity analysis was performed exclusively on patients with high CSF-tau protein levels (CSF-tau >330 pg/mL) to minimize inaccuracies of the diagnosis
Results:   From 495 AD patients reviewed, 192 patients (120 donepezil users and 72 controls) were eligible. Estimated annual decline of MMSE was 1.2 points (95% confidence interval (95%CI), 0.9–1.5) in the donepezil users, whereas it was 2.8 points (95%CI, 2.1–3.6) in the control group. The difference was statistically significant ( P  < 0.001). The sensitivity analysis demonstrated that these declines were 1.2 (95%CI, 0.8–1.6) and 3.1 (95%CI, 2.3–3.9) points in the donepezil users and control groups, respectively.
Conclusions:   Long-term donepezil use for at least 2 years appeared to be beneficial in maintaining cognition in AD patients. As the cholinergic central nervous system consistently degenerates over time, long-term use of donepezil may be an appropriate therapy. Discontinuation of donepezil may not be recommended as far as patients are in a stable condition.     

Music therapy-induced changes in behavioral evaluations, and saliva chromogranin A and immunoglobulin A concentrations in elderly patients with senile dementia

Objective:   To clarify music therapy-induced changes in behavioral evaluations, and saliva chromogranin A and immunoglobulin A concentrations in elderly patients with senile dementia.
Methods:   A music therapy group consisting of 8 elderly patients with dementia and a control group including eight similarly matched patients received a total of 25 1-h sessions of music therapy that were conducted twice weekly for 3 months. The Gottfries–Brane–Steen Scale, and the Behavioral Pathology in Alzheimer's Disease Rating Scale were used to evaluate behavioral changes. Saliva chromogranin A and immunoglobulin A were used to assess changes in stress and immunological status, respectively.
Results:   On the Gottfries–Brane–Steen Scale, the mean score for "different symptoms common in dementia" improved significantly after music therapy. The mean Behavioral Pathology in Alzheimer's Disease Rating Scale score for "paranoid and delusional ideation" also significantly improved ( P  < 0.05) after the intervention. While immunoglobulin A was slightly increased prior to intervention, at the 25th session, mean chromogranin A was significantly decreased ( P  < 0.05).
Conclusion:   In this study, the Gottfries–Brane–Steen Scale, the Behavior Pathology in Alzheimer's Disease Rating Scale, and immunoglobulin A concentrations were shown to have been affected by music therapy. However, as the number of subjects was small, further research is required in order to fully clarify the effects of music therapy.