The effectiveness of spaced retrieval combined with Montessori-based activities in improving the eating ability of residents with dementia.

AIMS: To explore the long-term effects of standardized and individualized spaced retrieval combined with Montessori-based activities on the eating ability of residents with dementia. BACKGROUND: Eating difficulty is common in residents with dementia, resulting in low food intake, followed by eating dependence, weight loss and malnutrition. DESIGN: A single-blinded and quasi-experimental design with repeated measures. METHODS: Ninety residents with dementia from four veterans' homes in Taiwan took part in this study. The intervention consisted of spaced retrieval combined with Montessori-based activities. Twenty-five participants in the standardized group received 24 intervention sessions over 8 weeks. Thirty-eight participants in the individualized group received tailored intervention sessions. The number of intervention sessions was adjusted according to the participant's recall responses in spaced retrieval. Twenty-seven participants in the control group received no treatment. The Chinese version of the Edinburgh Feeding Evaluation in Dementia was used, and eating amounts and body weight were measured pre-test, posttest and at 1-, 3- and 6-month follow-ups. Data were collected between July 2008-February 2010. Repeated measures of all dependent variables for the three groups were analysed by the linear mixed model. RESULTS: The standardized and individualized interventions could significantly decrease the scores for the Chinese version of the Edinburgh Feeding Evaluation in Dementia and increase the eating amount and body weight over time. CONCLUSION: Trained nurses in institutions can schedule the standardized or individualized intervention in usual activity time to ameliorate eating difficulty and its sequels.

Amyloid-beta (Aß) D7H mutation increases oligomeric Aß42 and alters properties of Aß-zinc/copper assemblies.

Amyloid precursor protein (APP) mutations associated with familial Alzheimer's disease (AD) usually lead to increases in amyloid ß-protein (Aß) levels or aggregation. Here, we identified a novel APP mutation, located within the Aß sequence (Aß(D7H)), in a Taiwanese family with early onset AD and explored the pathogenicity of this mutation. Cellular and biochemical analysis reveal that this mutation increased Aß production, Aß42/40 ratio and prolonged Aß42 oligomer state with higher neurotoxicity. Because the D7H mutant Aß has an additional metal ion-coordinating residue, histidine, we speculate that this mutation may promote susceptibility of Aß to ion. When co-incubated with Zn(2+) or Cu(2+), Aß(D7H) aggregated into low molecular weight oligomers. Together, the D7H mutation could contribute to AD pathology through a "double punch" effect on elevating both Aß production and oligomerization. Although the pathogenic nature of this mutation needs further confirmation, our findings suggest that the Aß N-terminal region potentially modulates APP processing and Aß aggregation, and further provides a genetic indication of the importance of Zn(2+) and Cu(2+) in the etiology of AD.

[Cognitive Abilities Screening Instrument, Chinese Version 2.0 (CASI C-2.0): administration and clinical application].

Abstract- The Cognitive Abilities Screening Instrument (CASI) has been commonly used in dementia research and clinical practice to evaluate a subject's cognitive abilities and to follow-up possible progression of dementia. It has a detailed manual for test administration and scoring in order to minimize testing errors. The Chinese version of CASI (CASI C-2.0) has been used in many clinical and epidemiological studies in Taiwan. Since cognitive abilities are influenced by education, and there are high rates of illiterate or low education individuals among the elderly in Taiwan, the normative data of CASI, including its total score and its cognitive domain scores, should be divided into different education ranges. In clinical practice, the cut-off scores in differentiating between dementia and normal are suggested to be: 49/50 for Education year = 0; 67/68 for Education years = 1-5; and 79/80 for Education years more than 6.

APOE ε4 increases the risk of progression from amnestic mild cognitive impairment to Alzheimer's disease among ethnic Chinese in Taiwan.

OBJECTIVE: To evaluate the effect of the apolipoprotein E (APOE) ε4 in the progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD) in ethnic Chinese people in Taiwan. METHODS: Subjects older than 60 years with normal cognition, MCI or AD were enrolled from the memory clinic from 2000 to 2008. Normal ageing and MCI subjects were evaluated with clinical and neuropsychological examinations annually, and their APOE genotypes were determined. RESULTS: A total of 326 normal ageing subjects, 304 amnestic MCI and 537 AD patients were recruited at baseline. The frequencies of APOE ε4 were 22.1% in normal ageing, 26.6% in MCI and 40.8% in AD patients. During the follow-up period (42.5±18.5 months), there were 227 MCI patients, and 248 normal ageing subjects received one or more annual follow-up evaluation. The ε4+carriers had a higher annual conversion rate than did the ε4-negative subjects either in the MCI (15.9% vs 9.0%) or in the normal ageing subjects (2.2% vs 0.7%). The mean survival time before progression to AD was 57.0 months for the MCI ε4+carriers, 85.9 months for MCI ε4-negative patients, 86.2 months for normal ageing e4+carriers and 120.8 months for normal ageing ε4-negative subjects. The adjusted hazard ratio of APOE ε4 for developing AD was 2.0 (95% CI 1.2 to 3.2) in MCI and 5.3 (95% CI 1.2 to 24.1) in normal ageing. CONCLUSION: APOE ε4 increased the risk of developing AD both in amnestic MCI and in normal ageing in a clinic-recruited ethnic Chinese population.

Accelerated hippocampal atrophy rates in stable and progressive amnestic mild cognitive impairment.

Studies suggest that smaller hippocampal volume predicts Alzheimer's disease (AD) in mild cognitive impairment (MCI). However, few studies have demonstrated decline rates in cognition and hippocampal volume in MCI subjects with stable clinical presentation. Furthermore, the effects of apolipoprotein E (ApoE) on the change rates of medial temporal structures and cognition in MCI are rarely investigated. Fifty-eight subjects with amnestic MCI and 20 normal aging elderly controls received annual neuropsychological and magnetic resonance imaging (MRI) assessments. Annual decline rates in neuropsychological test scores, hippocampal and amygdalar volumes were calculated. ApoE genotypes were examined. Nineteen (32.7%) MCI subjects converted to AD during an average 22.5-month follow-up period. The annual hippocampal atrophy rate was correlated with a decline in memory test scores. The presence of the ApoE varepsilon4 allele did not affect the change rates in neuropsychological test scores and medial temporal structures volume. Compared to subjects with stable MCI (MCI-S) and normal aging, progressive MCI (MCI-P) had the highest annual decline rates in cognition and hippocampal volume. Logistic regression analysis showed that higher annual decline rates in hippocampal volume and global cognitive test scores were associated with conversion to AD. Furthermore, although MCI-S subjects had little cognitive decline, their hippocampal atrophy rates were higher than those of normal aging controls. Therefore, accelerated hippocampal atrophy rates may be an early and important presentation in MCI subjects.

Survival of ethnic Chinese with Alzheimer's disease: a 5-year longitudinal study in Taiwan.

Survival time and mortality risk factors in patients with Alzheimer's disease (AD) have been documented in Western countries, but comparable information on the ethnic Chinese is scarce. We consecutively recruited 159 AD patients and 145 control subjects from the Memory Clinic of Taipei Veterans General Hospital. After admission to the study, each subject received clinical, neuropsychological, and psychiatric evaluation and apolipoprotein E genotyping. Survival status was followed for 5 years. Forty-six AD patients (28.9%) and 3 control subjects (2.1%) died during the 5-year follow-up period. The mean survival time for AD patients was 4.48 years (SD = 0.1 years) after the time of enrollment. Among individuals with AD, those with severe disease, older patients, and those experiencing hallucinations were at greater risk for increased mortality. As expected, AD shortened life expectancy in these patients. The factors found to correlate with a shorter life span may suggest effective health care strategies for AD patients.

Midlife risk factors for subtypes of dementia: a nested case-control study in Taiwan.

OBJECTIVE: To identify the midlife risk factors for subtypes of dementia newly developed later in life. METHODS: A nested case-control study was conducted on 157 demented cases and 628 comparison cases selected from 40,636 men and women who were enrolled from 1982 to 1992. Four comparison cases were frequency-matched on age, time at enrollment (within 6 months), gender, and residential township. Midlife risk factors included vascular risk factors (body mass index [BMI], total cholesterol, total triglycerides, blood glucose, cerebrovascular accident [CVA] history, diabetes mellitus history, and hypertension history), cigarette smoking, and alcohol consumption. Dementia assessments were ascertained through the computerized data linkage from National Health Insurance Database from 2000 to 2002 and clinically confirmed by neurologists or psychiatrists. Conditional logistic regression analysis was used to estimate the matched odds ratio (OR) and its 95% confidence intervals (CI) for each risk factor. RESULTS: A J-shaped relationship was observed between BMI (kg/m(2)) and dementia. The multivariate-adjusted ORs (95% CI) of developing dementia were 1.84 (1.02-3.33), 1.87 (1.08-3.23) and 2.44 (1.39-4.28), respectively, for BMIs of <20.5, 23.0-25.4, >or=25.5 compared with a BMI of 20.5-22.9 as the referent group (OR = 1.0). Similar findings were observed for Alzheimer disease (AD) and vascular dementia (VaD). The association between obesity (BMI >or=25.5) and both AD and VaD was statistically significant among cigarette smokers but not among nonsmokers. Additionally, history of CVA was a significant risk factor for VaD, but not for AD. CONCLUSION: Being underweight, being overweight, and a cerebrovascular accident in midlife may increase the risk of dementia in late life.

Conversion to dementia from questionable dementia in an ethnic Chinese population.

We investigated the conversion rate and the risk factors for conversion to dementia from questionable dementia in 124 ethnic Chinese subjects with questionable dementia at a memory clinic of a university hospital. They were evaluated annually based on cognitive testing, the clinical dementia rating scale, and a psychiatrist's interview for depression and anxiety. Apolipoprotein E genotyping was performed on 111 of these questionable dementia subjects. All subjects were evaluated at least twice during the follow-up period of 20.4 +/- 12.4 months. During that period, 42 questionable dementia subjects were diagnosed as having Alzheimer's disease, with an annual conversion rate to dementia of 19.9%. Compared with the 82 nonconverters, the 42 converters were significantly older, had lower cognitive, depression, and anxiety scores, and a higher frequency of the apolipoprotein E epsilon4 allele. Cox regression analysis revealed that the Alzheimer's disease converters had lower scores for orientation, short-term memory, and anxiety, and a higher frequency of the apolipoprotein E epsilon4 allele than the nonconverters.

Evaluating the uses of the total score and the domain scores in the Cognitive Abilities Screening Instrument, Chinese version (CASI C-2.0): results of confirmatory factor analysis.

BACKGROUND: The Cognitive Abilities Screening Instrument (CASI) consists of items which are designed to measure the nine domains of cognitive ability. Its total score is used clinically to represent the overall underlying cognitive ability of the patient. This study aimed to evaluate the justification of the uses of the all-domain-total-score as an overall cognitive measure and the domain scores as measures of designated individual cognitive ability. METHODS: To justify the use of total score of all the items as an overall measure of cognitive ability, a second-order confirmatory factor analysis was performed to examine whether the items in CASI contributed significantly to a common underlying construct. The uses of domain scores were also examined by inspecting the loadings of the items on their designated domains. The CASI data from 608 patients, 68 normal and 540 with Alzheimer's disease, were analyzed. RESULTS: The goodness-of-fit indices for the second-order factor model were as follows: CFI was 0.912 for WLSMV and 0.977 for WLSM; TLI and RMSEA values were 0.975 and 0.090 respectively. The loadings of the items on the common underlying construct are all salient (>0.3). The loadings of all but the long-term memory items on their respective subdomains were also salient. CONCLUSIONS: The items of the CASI C-2.0 were useful not only in profiling the correlated cognitive domain scores, but also in forming an overall measure of the underlying cognitive ability of the patients.

Behavioral and psychological symptoms in Taiwanese patients with Alzheimer's disease.

OBJECTIVE: To investigate the prevalence of and risk factors for behavioral and psychological symptoms in Taiwanese Alzheimer's disease (AD) patients. METHOD: Consecutive AD patients from the Memory Clinic of the Taipei Veterans General Hospital were studied. Cognitive function was evaluated using the Chinese version of the Cognitive Abilities Screening Instrument. Primary caregivers were interviewed for the Clinical Dementia Rating scale, the Barthel Index, and the Alzheimer's Deficit Scale. Behavioral and psychological symptoms were assessed using the Behavioral Pathology in Alzheimer's Disease Rating Scale. RESULTS: Of the 142 participants, 73 (50.7%) had at least one delusion. The most frequent delusion was delusion of theft (N=43, 30.3%). Thirty-five patients (24.6%) experienced hallucination. Fifty-seven patients (40.1%) had activity disturbances and 39 (27.5%) had aggression. Patients were divided into two subgroups according to the presence or absence of each cluster of symptoms, namely, delusions, hallucinations, activity disturbance, aggression, diurnal rhythm change, affective symptoms, and anxiety. There was no significant correlation between age, age at onset of dementia, number of years of education, and duration of illness and each cluster of symptoms. Correlation between severity of behavioral and psychological symptoms of dementia and cognitive decline was noted. CONCLUSIONS: This study revealed a high prevalence of behavioral and psychological symptoms of dementia in Taiwanese patients with AD and suggests that these symptoms are associated with cognitive deficit.

Correlation between platelet amyloid precursor protein isoform ratio and cognition in Alzheimer's disease.

This study analyzed whether platelet amyloid beta-protein precursor (AbetaPP) isoform ratio correlates with cognition or cognitive decline in patients with Alzheimer's disease (AD). Platelet AbetaPP isoform ratio was measured, and cognitive assessment was performed using the Mini-Mental State Examination (MMSE) in 66 AD patients at baseline (T0) and in 29 of these patients in a one-year follow-up (T1). There was a significant correlation between the AbetaPP isoform ratios and MMSE scores in the 66 AD patients at T0. The T1 subjects were divided into two groups: 12 "no decliners" (MMSE score, T1-T0 > or = 0) and 17 "decliners" (MMSE score, T1-T0 < 0). The decliners group showed a significantly greater reduction of AbetaPP isoform ratio from T0 to T1 than the no decliners group. However, the decline of the ratio did not correlate with the decline of MMSE score. These findings indicate that AbetaPP isoform ratio correlates with cognition, and reduction in this ratio may be a marker for cognitive decline in AD patients.

Magnetic resonance imaging segmentation techniques using batch-type learning vector quantization algorithms.

In this article, we propose batch-type learning vector quantization (LVQ) segmentation techniques for the magnetic resonance (MR) images. Magnetic resonance imaging (MRI) segmentation is an important technique to differentiate abnormal and normal tissues in MR image data. The proposed LVQ segmentation techniques are compared with the generalized Kohonen's competitive learning (GKCL) methods, which were proposed by Lin et al. [Magn Reson Imaging 21 (2003) 863-870]. Three MRI data sets of real cases are used in this article. The first case is from a 2-year-old girl who was diagnosed with retinoblastoma in her left eye. The second case is from a 55-year-old woman who developed complete left side oculomotor palsy immediately after a motor vehicle accident. The third case is from an 84-year-old man who was diagnosed with Alzheimer disease (AD). Our comparisons are based on sensitivity of algorithm parameters, the quality of MRI segmentation with the contrast-to-noise ratio and the accuracy of the region of interest tissue. Overall, the segmentation results from batch-type LVQ algorithms present good accuracy and quality of the segmentation images, and also flexibility of algorithm parameters in all the comparison consequences. The results support that the proposed batch-type LVQ algorithms are better than the previous GKCL algorithms. Specifically, the proposed fuzzy-soft LVQ algorithm works well in segmenting AD MRI data set to accurately measure the hippocampus volume in AD MR images.

The MCI study in Taiwan.

Veterans General Hospital started study for mild cognitive impairment (MCI) since 1996. We used clinical dementia rating (CDR) of 0.5 to define our questionable dementia (QD) subjects. These QD subjects received annual neuropsychological assessment in 5-year follow-up period. Annual conversion rate, apolipoprotein E (ApoE) genotype and neuropsychological risk factors for QD were investigated. We found a 19.9% person-year conversion rate for these QD subjects. Both of the poor cognitive performance and ApoE epsilon4 allele were risk factors for progressing to dementia. Based on the results of this study and the progress in the concept of MCI, we added more complex verbal and visual memory tests as well as MRI-based volumetry measurement in our subsequent research. Peterson's amnestic MCI criteria were used to diagnose our MCI subjects. In the 3-year follow-up period, the conversional rate was 18.2% person-year for MCI subjects, similar to our previous finding in QD. We found hippocampal volume was positively associated with cognitive performance. ApoE genotype had effect on hippocampal volume. Subjects with lower cognitive performance and smaller hippocampi had higher risk converting to AD. With rapidly expanding research on dementia and MCI worldwide, we are looking forward to seeing the integration in neurobiology, neuroimaging, and neurobehavior fields to establish a multidisciplinary approach to MCI and dementia.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy: two novel mutations in the NOTCH3 gene in Chinese.

BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary disorder caused by NOTCH3 mutations, usually localized to exons 3 and 4, and characterized by recurrent subcortical infarctions, dementia and leukoencephalopathy. So far, there has been only limited information about CADASIL in Chinese population. OBJECTIVES: To analyze the NOTCH3 mutations in ethnic Chinese in Taiwan with clinically suspected CADASIL and to characterize their clinical and molecular features. METHODS: Mutation analysis of NOTCH3 by direct nucleotide sequencing was performed in eight unrelated Chinese patients with clinically suspected CADASIL. Skin biopsy with ultrastructural studies by electronic microscopy was performed in four patients. RESULTS: Five NOTCH3 mutations, S118C, R141C, R332C, R544C and C977S, respectively, were identified from five patients, of which S118C and C977S are novel. None of these nucleotide sequence variations could be found among 50 healthy controls. Among the five mutations, two were in exon 4, and the other three were in exons 6, 11 and 18, respectively. Skin biopsy showed the presence of characteristic granular osmiophilic material only in the patient with the NOTCH3 mutation of R332C. CONCLUSION: Our study demonstrated the clinical and molecular features of CADASIL in Chinese patients and broadened the spectrum of NOTCH3 mutations. Lack of evidence of a strong clustering of mutations in a particular exon tentatively suggests that a comprehensive screening of NOTCH3 mutation is still necessary for molecular diagnosis of CADASIL in Chinese population.

The brain-derived neurotrophic factor gene as a possible susceptibility candidate for Alzheimer's disease in a chinese population.

Brain-derived neurotrophic factor (BDNF), a member of the neurotrophic factor family, may represent a candidate gene conferring susceptibility to Alzheimer's disease (AD). This is because it has an important role in neuronal survival, and a decreased central level of BDNF is observed in AD. Some previous studies, though not all, have demonstrated that BDNF C270T polymorphisms might be associated with AD susceptibility. We examined the association of the C270T polymorphisms with sporadic AD in a Chinese cohort of 175 AD patients and 189 controls. We also tested BDNF Val66Met-C270T haplotypes for an interaction with the apolipoprotein E upsilon4 (APOE4) allele in AD. The results showed that the frequency of the 66Val allele was significantly lower in AD than controls (p = 0.031), but no significant difference in C270T allele or genotype frequencies was observed between AD cases and controls. Global case-control haplotype analysis showed that there is significant difference in haplotype distribution between both groups (p = 0.033). Stratification of the data according to the APOE status showed that in APOE4 allele bearers there was no significant difference in the frequency of haplotype 66Val-270C between AD and controls (p = 0.125), although there was a significant difference between the two groups in non-APOE4 carriers (p = 0.002). These results suggest that BDNF genetic variation may possibly affect the risk for AD, particularly in subjects who are negative for APOE4.

Family members favor disclosing the diagnosis of Alzheimer's disease.

BACKGROUND: Past negative attitudes towards patients with Alzheimer's disease (AD) have changed in recent years. However, the disclosure of AD diagnosis to patients and family remains an unresolved issue. In this study, we surveyed the family members of neurological patients in Taiwan for the purpose of assessing their attitudes towards the disclosure of AD diagnosis. METHODS: The study sample consisted of family members (150, age range 23-89 years, mean 55.0+/-14.3) who accompanied patients to a neurology outpatient clinic from September 15 to November 24, 2003. The subjects were given an Attitude Questionnaire on AD Disclosure. RESULTS: An overwhelming majority (93%) of subjects favored disclosure of the diagnosis if, hypothetically, they personally were affected by AD. However, a smaller majority of family members (76%) favored disclosure of the diagnosis to current AD patients. Reasons for favoring disclosure included a patient's or family member's right to know, the possibility of assistance in coping with and understanding dementia, and slowing down the progression of the disease by early treatment, as well as the increased probability of accepting treatment and life activity training. Reasons for favoring the withholding of disclosure included the risk of causing the patient emotional disturbance, worsening the disease, the irrelevance of disclosure to drug therapy, and the possibility of causing suicidal ideation. Subjects' attitudes towards disclosure of AD diagnosis were unaffected by their knowledge of dementia, the presence of a family member with AD, their role as the primary caregiver, the length of time that AD symptoms persisted, and the number of hours per day spent in caring for AD patients. CONCLUSIONS: In Taiwan, family members of neurological patients strongly favor being informed and the disclosure of AD diagnosis to the family.

Conceptualization and measurement of getting lost behavior in persons with early dementia.

BACKGROUND: The primary purpose of this preliminary research was to describe the psychometric properties of a newly-developed Everyday Spatial Questionnaire for Dementia-patient version (ESQD-P) in a Chinese population. A secondary goal was to assess the relationship between executive functions and wayfinding strategy application. The ESQD-P is a measure for the phenomenon of 'getting lost behavior' (GLB) reported by early Alzheimer's disease sufferers, based on the concept of spatial problem-solving. METHODS: With a cross-sectional descriptive design, the ESQD-P was validated by examining for internal consistency, construct validity, concurrent validity, and exploratory factor analyses among 116 outpatients in the memory disorder clinic of a veterans' general hospital in Taiwan. Other variables included were: global cognition, measured by the Cognitive Abilities Screening Instrument; stages of dementia, measured by the Clinical Dementia Rating Scale; and depressive symptoms, measured by the Geriatric Depression Scale-Short Form. RESULTS: Findings indicated that the Chinese ESQD-P is a reliable instrument for measuring GLB (internal consistency alpha = 0.73). A five-factor solution explained 55.45% of the score variance, while the correlations between the patient and proxy versions of this instrument yielded an acceptable concurrent validity. Executive functions can predict both global and analytic wayfinding strategies. CONCLUSIONS: GLB may be explained in part by declining executive functions. Deleting the coping strategies subscale may improve psychometric properties of the ESQD-P.

Cognitive reserve: a SPECT study of 132 Alzheimer's disease patients with an education range of 0-19 years.

This study examines the associations between education, cerebral perfusion, and cognitive test performance among 132 patients with Alzheimer's disease. The participants had had between 0 and 19 years of formal schooling, and had either mild or moderate dementia according to the Clinical Dementia Rating Scale. Cerebral perfusion was evaluated by the (99m)Tc-hexamethylpropylene amine oxime single photon emission computed tomography. The Mini-Mental State Examination and the Cognitive Abilities Screening Instrument were used to assess cognitive performance. For patients at each clinical dementia severity level, statistical parametric mapping was used to examine voxel by voxel the association between education and cerebral perfusion, and Pearson's correlation coefficients were calculated between education and cognitive test scores. Years of formal schooling had negative associations with cerebral perfusion and positive associations with cognitive test scores. The brain regions showing a significant education effect on perfusion involved bilateral posterior association areas in mild dementia, and bilateral parieto-temporo-frontal areas in moderate dementia. The present findings indicate that the cognitive reserve effect starts at the low end of the education range. They also suggest that the main effect of more education is a more facile use of alternative brain circuits instead of locally increased synaptic connections.