Determinants of long-term care service use by persons with dementia: A national dementia registry study conducted in Taiwan.

BACKGROUND: This study investigated the determinants and use of Taiwan's long-term care (LTC) Plan Version 2.0 (LTC 2.0) services by persons with dementia (PWDs) and their caregivers. METHODS: In total, 1268 PWD-caregiver dyads were enrolled for analysis from a national dementia registry. Andersen's Behavioral Model of Health Services Use was used to investigate the association of LTC service use with several factors, namely the demographic data of PWDs and their caregivers, migrant caregiver employment, monthly household income, caregiver burden as determined by the Zarit Burden Interview (ZBI), Mini-Mental State Examination score, Clinical Dementia Rating scores, neuropsychiatric inventory scores for the behavioral and psychological symptoms of dementia, and PWDs' activities of daily living (ADLs). RESULTS: Among the studied family caregivers, 81.4% did not use LTC resources. A multivariable logistic analysis revealed that aberrant motor behaviors (odd ratio [OR] = 1.31, 95% confidence interval [CI] = 1.10-1.56, p = 0.003), dysfunction in ADLs (OR = 1.06, 95% CI = 1.02-1.10, p = 0.002), higher ZBI scores (OR = 1.02, 95% CI = 1.01-1.03, p = 0.004), not residing with family members (OR = 1.88, 95% CI = 1.32-2.66, p < 0.001), and not employing a migrant caregiver (OR = 4.41, 95% CI = 2.59-7.51, p < 0.001) were the factors most significantly associated with LTC service use. CONCLUSION: Factors such as whether PWDs live alone, specific neuropsychiatric symptoms, and impaired function should be considered in future policy amendments to provide required activities and care resources for PWDs and their caregivers.

Predictors of caregiver burden in aged caregivers of demented older patients.

BACKGROUND: Dementia in the oldest-old is projected to increase exponentially as is the burden of their caregivers who may experience unique challenges and suffering. Thus, we aim to investigate which factors are associated with older caregivers' burden in caring demented outpatients in a multicenter cohort. METHODS: Patients and their caregivers, both aged ≧65 years, in the National Dementia Registry Study in Taiwan (T-NDRS) were included in this study. Caregiver burden was measured with the short version of the Zarit Burden Interview (ZBI). The correlations between the ZBI scores and characteristics of caregivers and patients, including severity of dementia, physical comorbidities, instrumental activities of daily living (IADL), neuropsychiatric symptoms assessed by the Neuropsychiatric Inventory (NPI), and family monthly income, were analyzed. RESULTS: We recruited 328 aged informal caregiver-patient dyads. The mean age of caregivers was 73.7 ± 7.0 years, with female predominance (66.8%), and the mean age of patients was 78.8 ± 6.9 years, with male predominance (61.0%). Multivariable linear regression showed that IADLs (ß = 0.83, p < 0.001) and NPI subscores of apathy (ß = 3.83, p < 0.001)and irritability (ß = 4.25, p < 0.001) were positively associated with ZBI scores. The highest family monthly income (ß = - 10.92, p = 0.001) and caregiver age (ß = - 0.41, p = 0.001) were negatively correlated with ZBI scores. CONCLUSIONS: Older caregivers of older demented patients experience a higher care burden when patients had greater impaired functional autonomy and the presence of NPI symptoms of apathy and irritability. Our findings provide the direction to identify risky older caregivers, and we should pay more attention to and provide support for these exhausted caregivers.

The Clinical Features and Therapeutic Outcomes of Young Adults with Cryptococcal Meningitis.

OBJECTIVE: No previous study has reported on the clinical characteristics of cryptococcal meningitis (CM) focusing solely on young adults. PATIENTS AND METHODS: Ninety-nine adult patients with CM (64 men and 35 women) were enrolled, of whom 26 were classified into the young adult group (≤ 40 years) and 73 into the non-young adult group (> 40 years). The modified Rankin scale (mRS) was used to evaluate the outcomes of the survivors at the time of discharge and at 1 year of follow-up. The clinical characteristics and laboratory data between 1) the young adult CM patients with and without acquired immunecompromised syndrome and 2) the male and female young adult CM patients were compared. The prognostic factors of the young adult CM patients were also analyzed. RESULTS: The young adult group had a higher incidence of headache as the clinical presentation which may have been due to the higher intracranial pressure in this group. The overall mortality rate of the young adults with CM was high (38.5%, 10/26), but no significant prognostic factors were found. In followup studies of the neurologic deficits, the young adult survivors had better outcomes (mRS scores = 0-2) than the non-young adult group at discharge and 1 year after discharge. CONCLUSION: The young adult CM patients had a higher incidence of headache as the clinical presentation. Although the mortality rate in the young adult CM patients was high, the survivors had better neurologic outcomes.

The Clinical Characteristics and Therapeutic Outcomes of Escherichia Coli Meningitis in Adults.

BACKGROUND: To examine the clinical characteristics and therapeutic outcome of Escherichia (E.) coli adult bacterial meningitis (ABM). METHODS: The demographic data, clinical and laboratory features and therapeutic outcome of 25 E. coli ABM patients were examined retrospectively. The clinical features of the reported E. coli ABM cases were also included for analysis. RESULTS: The 25 E. coli ABM patients included 12 women and 13 men, aged 33-78 years (mean= 59.9). Of these 25 patients, 13 had a postneurosurgical state as the underlying condition. As to the underlying medical conditions, diabetes mellitus was the most common, found in 9 of the 25 cases. Of the clinical manifestation, severe neurologic manifestations including altered consciousness (19), hydrocephalus (10), seizure (7) acute/subacute cerebral infarct (5), brain abscess (2), subdural empyema (1) and spinal abscess (1) were found, and the other clinical features included fever (21), septic shock (8), bacteremia (6) and hyponatremia (3). With treatment, the mortality rate was more than 44.0% and the presence of septic shock was a significant prognostic factor. With literature review, 29 community-acquired and 12 postneurosurgical E. coli ABM cases were enrolled, and severe neurologic manifestation and high mortality rate were also found. CONCLUSIONS: This preliminary overview of E. coli ABM revealed the underlying conditions, severe neurologic manifestation and high mortality rate. Further large-scale, prospective study is needed for a better delineation of this specific infectious syndrome of adult E. coli meningitis.

The clinical characteristics and therapeutic outcomes of cryptococcal meningitis in elderly patients: a hospital-based study.

BACKGROUND: The elderly, and especially those with an immuno-compromised status, are vulnerable to infectious diseases. The purpose of this study was to examine the clinical characteristics and therapeutic outcomes of cryptococcal meningitis (CM) in elderly patients in Taiwan. METHODS: Ninety-nine adult patients with CM were identified during a 15-year study period (2002-2016), of whom 38 elderly (≥ 65 years) patients (16 men and 22 women, median age 72.9 years; range 65-86 years) were included for analysis. The clinical characteristics and therapeutic outcomes of these patients were analyzed and compared to non-elderly adult patients (< 65 years) with CM. RESULTS: Among the 38 patients, diabetes mellitus was the most common underlying condition (15), followed by adrenal insufficiency (7), malignancy (6), hematologic disorders (5), chronic obstructive pulmonary disease (5), autoimmune diseases (3), liver cirrhosis (3) and acquired immunodeficiency syndrome (1). Altered consciousness (29), fever (21) and headache (17) were the leading clinical manifestations. Positive cerebrospinal fluid and blood cultures for Cryptococcus (C.) neoformans were found in 26 and 9 patients, respectively. There were significant differences in gender, altered consciousness and recent cerebral infarction between the elderly and non-elderly groups. The elderly group had a high mortality rate (36.8%, 14/38), and the presence of cryptococcemia was the most significant prognostic factor. CONCLUSIONS: This study offers a preliminary view of the clinical characteristics of CM in the elderly. The results suggest that elderly patients (≥ 65 years) are more vulnerable to CM than adults aged < 65 years. Compared to the non-elderly group, the elderly group had female predominance, higher rates of altered consciousness and recent cerebral infarction as the clinical presentation. The presence of cryptococcemia was a significant prognostic factor in the elderly group. This study is limited by the small number of patients, and further large-scale studies are needed to better delineate this specific infectious syndrome.

Clinical Characteristics and Therapeutic Outcomes of Postneurosurgical Bacterial Meningitis in Elderly Patients over 65: A Hospital-based Study.

PURPOSE: To investigate the clinical characteristics, laboratory features and prognostic factors of elderly patients with postneurosurgical bacterial meningitis. METHODS: Five hundred and forty patients with adult bacterial meningitis (ABM) were collected from 1986-2015, of whom 167 were ≥ 65 years. Of these 167 elderly patients, 82 had postneurosurgical infections and 85 had spontaneous infections. Clinical, laboratory and therapeutic data of these two groups were compared. RESULTS: The 82 elderly ABM patients with postneurosurgical infections included 48 men and 34 women with a median age of 71 years (range: 65-84 years). In addition to the postneurosurgical condition, the other most common underlying conditions included diabetes mellitus (29.3%) and hydrocephalus (29.3%). The major clinical presentations were fever (80.5%), altered consciousness (50.0%), hydrocephalus (43.9%), seizure (24.4%) and septic shock (15.9%). Of the implicated pathogens, staphylococcal species (spp.) were the most common (31.7%), followed by Acinetobacter spp. (12.2%), Enterobacter spp. (7.3%), Pseudomonas spp. (7.3%), Enterococcus faecalis (7.3%) and Escherichia coli (6.1%). The implicated staphylococcal spp. had a high rate of non-susceptibility to methicillin (84.6%), and the implicated Acinetobacter spp. and Enterobacter spp. had non-susceptible rates to ceftazidime of 60% and 50%, respectively. The mortality rate was 28.1%, and septic shock was the most significant prognostic factor. Compared with the clinical characteristics of the other 85 elderly patients with spontaneous ABM, there were significant differences in underlying condition, clinical and laboratory features and therapeutic outcomes. CONCLUSIONS: Elderly patients accounted for 30.9% of all cases of ABM, of whom 49.1% had postneurosurgical ABM. The clinical characteristics of the elderly patients with postneurosurgical ABM were non-specific, and cerebrospinal fluid studies were needed to confirm the diagnosis. The mortality rate of this group of patients was high, and septic shock was an important prognostic factor. The clinical and laboratory features and therapeutic outcomes were different between the elderly patients with postneurosurgical and spontaneous ABM.

Predictors of live-in migrant caregiver employment for people with dementia in Taiwan.

BACKGROUND: With the increasing number of individuals with dementia, families have hired an increasing number of live-in migrant caregivers (LIMCs). Currently, limited evidence is available regarding the influence of long-term care resource utilization on the hiring of LIMCs for caring for individuals with dementia in Taiwan. METHODS: We recruited individuals with dementia who did not hire LIMCs and their primary family caregivers from nine hospitals in Taiwan as baseline. Multivariable logistic regression was used to evaluate the utilization of long-term care resources for individuals with dementia and other factors that may affect the decision to hire LIMCs. RESULTS: The users of non-long-term care resources had the highest likelihood of hiring LIMCs (odds ratio [OR] = 4.24, 95% CI, 2.30-7.84). Compared with spouses, nonimmediate family caregivers (OR = 3.40, 95% CI, 1.16-9.90) were significantly more likely to hire LIMCs. A higher likelihood of hiring LIMCs was observed for those with Lewy body dementia compared with other individuals (OR = 2.31, 95% CI, 1.03-5.14). Compared with individuals who did not hire LIMCs, those who hired LIMCs exhibited higher scores on the Neuropsychiatric Inventory (NPI) and higher severity of individual NPI items. CONCLUSION: Hiring LIMCs is strongly correlated with the utilization of non-long-term care resources and is influenced by the dynamics between individuals with dementia and their primary family caregivers. A higher likelihood of hiring LIMCs was observed for individuals with Lewy body dementia and individuals with elevated NPI scores compared with their counterparts. Given these observations, various support strategies and interventions should be tailored to the specific requirements of individuals with dementia and their families.

Using fiber tractography and diffusion kurtosis imaging to evaluate neuroimaging changes in patients with cerebrotendinous xanthomatosis after stopping chenodeoxycholic acid treatment for three years.

BACKGROUND: The aim of this study was to use tractography and diffusion kurtosis imaging (DKI) to evaluate cerebral white matter (WM) changes in patients with cerebrotendinous xanthomatosis (CTX) after stopping chenodeoxycholic acid (CDCA) treatment. METHODS: Two siblings with CTX aged 40 and 38 years, respectively, who had been diagnosed with CTX for 16 years were enrolled. They had received CDCA treatment from 2005 until 2015, after which CDCA was no longer available in Taiwan. Serial brain magnetic resonance imaging (MRI) studies were used to record brain changes, and a seres of neuropsychiatric tests were used to evaluate cognitive changes 3 years after stopping CDCA treatment. RESULTS: The conventional MRI studies revealed progressive changes in dentate nuclei and surrounding cerebellar hemispheres, but no obvious changes in cerebral white matter (WM). Tractography captured in 2018 showed a general reduction in fiber density, especially involving frontal lobe fibers, compared to 2015. In addition, the DKI studies performed in 2018 showed a decreased axonal water fraction in diffuse WM structures and increased RadEAD in frontal WM. Comparisons of the neuropsychiatric test results between 2015 and 2018 showed a marked decline in executive function including design fluency, digit backward span and digit forward span, and this cognitive impairment highly suggested frontal lobe dysfunction. CONCLUSIONS: This study may suggest that cerebral tractography and DKI study results can identify changes in cerebral WM in CTX patients shortly after stopping CDCA treatment, and that they may have a better correlation with the results of neuropsychiatric tests.

Factors associated with burden among male caregivers for people with dementia.

BACKGROUND: There is a dearth of information on male dementia caregivers in Asia and, in particular, on the factors relating to caregiver burden. We aimed to identify factors that may be associated with burden among male caregivers of people with dementia (PWD). METHODS: Data were collected from a national dementia registration survey. The caregiver burden was measured with the short version of the Zarit Burden Interview (ZBI). We analyzed the correlation between ZBI scores and variables, such as demographic data of PWD and their male caregivers, caregivers' monthly income, the relationship between PWD and caregivers, the severity of dementia, physical comorbidities and activities of daily living (ADL) of PWD, and neuropsychiatric symptoms assessed by the Neuropsychiatric Inventory (NPI). RESULTS: A total of 509 PWD and their male caregivers were included. The majority of caregivers were sons (72.1%) and husbands (22.0%). Sons had higher ZBI scores than husbands (28.5 ± 15.2 vs 22.0 ± 17.0; p < 0.001). Multivariable linear regression showed that sons as caregivers (ß = 7.44, p = 0.034), ADL (ß = 0.52, p = 0.002), and NPI_severity subscore of apathy (ß = 2.74, p = 0.001) were positively associated with ZBI scores. CONCLUSION: Poor ADL and apathy in PWD and being a patient's son were associated with higher levels of burden among male dementia caregivers. Effective interventions are needed to assist male caregivers in accomplishing their caregiving role and at the same time to alleviate their caregiver burden.

A CD33 frameshift variant is associated with neuromyelitis optica spectrum disorders.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is a rare neuroimmunology disorder predominantly affecting the East Asia population, the reason for this preference remains unknown. Genetic factors such as polymorphisms in human leukocyte antigen (HLA) and interleukins (IL) genes have been reported. Although the familial occurrence of NMOSD is rare, it supports that genetic factors may play a role. METHODS: Whole exome sequencing (WES) study was performed on the affected mother and daughter, as well as the unaffected father in a Taiwanese family with NMOSD. A cohort of 19 sporadic patients with aquaporin 4 antibody (AQP4-Ab) positive NMOSD was also recruited; all fulfilled the 2015 International NMOSD Diagnosis Criteria. Sanger sequencing was performed on exon 4 of the CD33 gene on the sporadic NMOSD cohort. RESULTS: WES study revealed a 19 base pair deletion in exon 4 of the CD33 gene, resulting in frameshift premature truncating protein, which segregated with the affected status. CD33 was the most likely candidate gene due to its known function in immune regulation. A total of 19 sporadic NMOSD patients were tested using Sanger sequencing, including 3 patients with other concomitant autoimmune disorders. Two additional NMOSD patients were found to have the same CD33 frameshift variant, which accounts for 19.04% of all NMOSD patients, and 15% following correction for the familial cases; compared to 2% in Taiwanese population controls. CONCLUSION: In this study, we identified a 19 base pair deletion in the CD33 gene may be a potential risk locus for NMOSD, which is predicted to cause loss of function of CD33. The loss of CD33 inhibitory function may affect the regulation of the immune system in NMOSD patients. This finding requires further larger cohorts of NMOSD patients and functional study to corroborate.

High incidence of severe neurological manifestations and high mortality rate for adult Listeria monocytogenes meningitis in Taiwan.

The clinical characteristics and therapeutic outcomes of adult Listeria monocytogenes meningitis are not commonly examined in isolation in the literature. During a study period of 19 years (2000-2018), 366 patients with culture-proven adult bacterial meningitis (ABM) were identified in the author's hospital (264 patients in 2000-2010 and 102 patients in 2011-2018). Of the 366 ABM patients, 330 had monomicrobial infections while the other 36 had mixed infections. L. monocytogenes infection was identified in 11 of the 330 patients with monomicrobial ABM (3 in 2000-2010 and 8 in 2011-2018). These 11 patients included 5 males and 6 females, aged 47 to 76 years (median age = 61.7). None of the 11 patients had a postneurosurgical state as the underlying cause, but 3 of them contracted the infection nosocomially. Common underlying conditions included liver cirrhosis (4), systemic malignancy (3), diabetes mellitus (3), and renal disease (2). The most common clinical manifestations were fever (11), altered consciousness (8), seizure (8), bacteremia (7) and hydrocephalus (5). The therapeutic result revealed a mortality rate of 72.7% (8/11), but no significant prognostic factors were identified. The clinical features of 8 additional Taiwanese L. monocytogenes ABM patients reported in the literature, were also included for analysis. The present study revealed an increase in L. monocytogenes ABM in recent years and most patients presented with severe neurological manifestations. The current study is a preliminary overview of L. monocytogenes meningitis in adults and a further large-scale study is needed for improved delineation of this specific infectious syndrome.

The clinical characteristics, implicated pathogens and therapeutic outcomes of culture-proven septic cavernous sinus thrombosis.

In this magnetic resonance imaging-based study, we investigated the clinical features, neuroimaging features and therapeutic outcomes of 14 adults (eight men and six women; mean age 60.4 years; range 37-77 years) with septic cavernous sinus thrombosis (CST). Of the underlying conditions, 10 had diabetes mellitus and 13 had concomitant sphenoid sinusitis. Headache (n = 13) and ophthalmoplegia (n = 13) were the most common clinical presentations, followed by fever (n = 9) and other neuro-vascular signs and symptoms. The duration from the onset of symptoms to diagnosis ranged from 1 to 61 days, and more than 64% (9/14) of the septic CST patients were diagnosed >7 days after symptom onset. Expansion of the cavernous sinus was the most common neuroimaging feature, followed by convexity of the lateral wall of the cavernous sinus (5) and filling defect of the cavernous sinus (4). Staphylococcal species (spp.) was the most commonly implicated pathogen, followed by Aspergillus spp. Despite treatment, 7% (1/14) of the patients died in the hospital and 67% (8/12) of the survivors had neurological deficits. The duration of onset-to-diagnosis and the presence of hemiparesis were significant prognostic factors. These results provide a preliminary view of this uncommon infectious syndrome. Further large-scale studies are needed to better delineate septic CST in adults.

Intra-family phenotype variations in familial neuromyelitis optica spectrum disorders.

BACKGROUND: The aim of the current study was to examine intra-family phenotype variations in familial neuromyelitis optica (NMO) spectrum disorder. METHODS: The clinical presentation and neuroimaging features of two family members (mother and daughter) from a NMO spectrum disorder family (index family) were analyzed. Multiplex polymerase chain reaction was performed based on targeted re-sequencing on the AQP4 gene and the human leukocyte antigen (HLA) loci. The clinical and neuroimaging features of the members of six other previously reported NMO spectrum disorder families were also included for analysis. RESULTS: In the core family, the mother was aged 39 at disease onset and the initial presentation was spinal cord involvement, whereas the daughter was 22 years old at disease onset and the initial presentation was brainstem involvement. No coding pathogenic variants or single nucleotide polymorphisms of the AQP4 gene were identified in the mother, daughter or father. As for HLA genotyping, the HLA-DRB1*03 and HLA-DPB1*04 alleles were shared by the mother and daughter. The HLA-DPB1*05 was present in the affected daughter and was inherited from the unaffected father. As for the other six reported families with familial NMO spectrum disorder, four mother-daughter pairs had a different age at disease onset and/or a different initial presentation. The other two affected family groups were sister-sister pairs; they had a similar age of onset and similar initial presentations. CONCLUSION: The present study offers a preliminary view of the clinical and neuroimaging features of patients with familial NMO spectrum disorder. Clinical heterogeneities were found among the family members, especially the mother and daughter pairs. The presence of risk allele HLA-DR*03:01 may be an important genetic finding for familial NMO spectrum disorder patients. To the best of our knowledge, this clinical heterogeneity has not been previously examined or reported in the literature. For better delineation of the intra-familial phenotype variations in familial NMO spectrum disorder, further large-scale studies are needed.

The clinical characteristics of spontaneous Gram-negative bacterial meningitis in adults: A hospital-based study.

The epidemiologic trend of acute bacterial meningitis can change more dramatically than any other bacterial disease, and a decrease in spontaneous adult bacterial meningitis (ABM) has been noted in serial studies of the epidemiologic trend of ABM in Taiwan. The purpose of this study was to analyze the clinical characteristics, laboratory data and therapeutic outcomes of 149 patients with spontaneous Gram-negative (G(-)) ABM collected during a study period of 31 years (1986-2016). The 149 patients included 107 men and 42 women, aged 18-86 years. The common underlying conditions were diabetes mellitus, liver cirrhosis and alcoholism, and the leading clinical presentations were fever, altered consciousness and septic shock. Compared the clinical characteristics of the patients identified in the study period of 2001-2106 to the patients identified in the study period of 1986-2000, the former group of patients had a significantly higher incidence of systemic malignance. In the recent 16 years (2001-2016), Klebsiella pneumoniae, Pseudomonas spp. and Escherichia coli were the leading three implicated bacterial pathogens of spontaneous G(-) ABM, accounting for 61.3% (38/62), 11.3% (7/62) and 11.3% (7/62%) of all cases, respectively. The overall mortality rate from spontaneous G(-) ABM was high (47.0%, 70/149) and the presence of septic shock and lower cerebrospinal fluid glucose level were significant prognostic factors. Because of the decreasing incidence of spontaneous ABM in Taiwan, close examination of this specific infectious syndrome is important in order to monitor the epidemiologic trend and improve the therapeutic strategy.

APOE-MS4A genetic interactions are associated with executive dysfunction and network abnormality in clinically mild Alzheimer's disease.

PURPOSE OF THE RESEARCH: Although single nucleotide polymorphisms of membrane-spanning 4A (MS4A) (rs670139) and several other susceptibility genes have shown interaction effects on the risk of Alzheimer's disease (AD), little is known about the interaction effects of apolipoprotein E (APOE) with MS4A (rs670139) on cognitive performances, and the underlying pathogenesis is unclear. The study aimed to investigate the APOE-MS4A (rs670139) interaction effects on cognitive performances, cortical volumes, and functional connectivity (FC) in brain networks. PRINCIPAL RESULTS: Cognitive performances were characterized in each genotypic group, and were compared between normal controls and patients in each genotypic group. APOE-MS4A interaction effects on memory and executive function scores, cortical volumes, and FC in brain networks were demonstrated. Significant effects of APOE-MS4A interactions on FC were observed in executive control network (ECN) (T maxima = 4.99, false discovery rate-corrected p < .001), the calculation score (F3, 87 = 6.218; p = .015), and the volume in prefrontal (F3, 87 = 4.374; p = .039) and orbitofrontal cortices (F3, 87 = 6.022; p = .016). The calculation score was correlated with each frontal volume (cc) (ρ = 0.304; p = .004) and genetic interaction-associated FC in ECN (ρ = 0.282; p = .008). Variations in genotypes affected the relationship between the calculation score and each frontal volume (cc). MAJOR CONCLUSIONS: These findings indicate that the genetic interaction effects on FC in ECN might contribute to pathogenic mechanisms underlying the interaction effects of APOE-MS4A on calculation ability in AD.

Adequacy of nutrition and body weight in patients with early stage dementia: The cognition and aging study.

BACKGROUND & AIMS: Recent evidence highlights the effects of obesity, diabetes and hypertension in the development of Alzheimer's disease. Involuntary body weight changes in patients with different stages of dementia can be related to clinical factors of the patient per se or support from their caregivers. Understanding the interactions among factors is important to establish a monitoring paradigm to guide treatment strategies. METHODS: A total of 345 patients with very mild (n = 224) and mild stage (n = 121) dementia were enrolled from a multi-disciplinary dementia clinic. Clinical data (comorbidities, Mini-Mental State Examination [MMSE] scores, neuropsychiatric inventory [NPI] scores, eating behavior questionnaire), nutritional state (Mini-Nutritional Assessment [MNA] or MNA short form [MNA-SF]) and body mass index (BMI) were recorded. Nutritional state and BMI served as the two major outcome measures, and factors for analysis included diagnosis, dementia severity and clinical data. RESULTS: There was a significant correlation between MNA-SF and MNA (r = .898, p < 0.01), but a 24% mismatch in case dislocation was found using the at-risk or malnutrition criteria. Factors related to obesity included male sex, higher MNA-SF and MNA scores, diabetes mellitus and hypertension, while acceptable discrimination for obesity (BMI≧23 kg/m2) was obtained with a MNA-SF score of 12/13 or MNA score of 21/22. NPI was the only independent factor related to both MNA-SF (ß = -.06, P < 0.001) and MNA (ß = -.1, P < 0.001). A BMI of 22-23 kg/m2 was adequate in this group of patients with early stage dementia from nutritional and comorbidity perspectives. After controlling for BMI, the patients with advanced dementia had higher swallowing problem and appetite change scores. CONCLUSIONS: In these patients with early stage dementia, a higher BMI indicated adequate nutritional status and higher MMSE, but also higher rates of comorbidities, diabetes mellitus and hypertension.

The clinical characteristics of adult cryptococcal meningitis patients who died within one year of treatment with a focus on those with early mortality.

Cryptococcal meningitis (CM) is a serious infectious disease of the central nervous system, and associated brain injuries can be found in the very early stage of disease. In this study, 92 adult CM patients (59 men, 33 women; median age 54.66 years, range 20-86 years) were enrolled, and their clinical, laboratory, neuroimaging features and therapeutic outcomes were analyzed. Two main clinical comparative analyses of the clinical characteristics and laboratory and neuroimaging features were made in this study. The first compared clinical differences between the survivors and non-survivors of all enrolled patients, and the second compared differences between the following three groups: Group I, the patients who died within 14 days of initiating treatment; Group II, the patients who died within 15 days to 1 year of initiating treatment, and Group III, the patients who survived for more than 1 year after initiating treatment. Prognostic factors including initial altered consciousness, increased cerebrospinal fluid (CSF) lactate level and the presence of cryptococcemia were significantly different between the different groups. The patients with early mortality had a higher CSF lactate level and higher rate of cryptococcemia. The presence of cryptococcemia was an important prognostic factor, and the patients with cryptococcemia had a higher incidence of positive CSF India ink stain. Further large-scale studies are needed to delineate the clinical and laboratory features of CM patients with early mortality.

ABCA7 polymorphisms correlate with memory impairment and default mode network in patients with APOEε4-associated Alzheimer's disease.

BACKGROUND: Since both APOE and ABCA7 protein expression may independently reduce neuritic plaque burden and reorganize fibrillar amyloid burden-mediated disruption of functional connectivity in the default mode network, we aimed to investigate the effect of the APOE-ABCA7 interaction on default mode network in Alzheimer's disease. METHODS: Two hundred and eighty-seven individuals with a diagnosis of typical Alzheimer's disease were included in this study. Memory was characterized and compared between APOE-ε4+ carriers and APOE-ε4 non-carriers within ABCA7 rs3764650T allele homozygous carriers and ABCA7 rs3764650G allele carriers, respectively. Two-way analysis of variance was used to identify a significant interaction effect between APOE (APOE-ε4+ carriers versus APOE-ε4 non-carriers) and ABCA7 (ABCA7 rs3764650T allele homozygous versus ABCA7 rs3764650G allele carriers) on memory scores and functional connectivity in each default mode network subsystem. RESULTS: In ABCA7 rs3764650G allele carriers, APOE-ε4+ carriers had lower memory scores (t (159) = - 4.879; P < 0.001) compared to APOE-ε4 non-carriers, but APOE-ε4+ carriers and APOE-ε4 non-carriers did not have differences in memory (P > 0.05) within ABCA7 rs3764650T allele homozygous carriers. There was a significant APOE-ABCA7 interaction effect on the memory (F3, 283 = 4.755, P = 0.030). In the default mode network anchored by the entorhinal seed, the peak neural activity of the cluster that was significantly associated with APOE-ABCA7 interaction effects (P = 0.00002) was correlated with the memory (ρ = 0.129, P = 0.030). CONCLUSIONS: Genetic-biological systems may impact disease presentation and therapy. Clarifying the effect of APOE-ABCA7 interactions on the default mode network and memory is critical to exploring the complex pathogenesis of Alzheimer's disease and refining a potential therapy.

Clinical and molecular genetic features of cerebrotendinous xanthomatosis in Taiwan: Report of a novel CYP27A1 mutation and literature review.

BACKGROUND: Cerebrotendinous xanthomatosis (CTX) is an autosomal recessive lipid storage disorder associated with mutations in the CYP27A1 gene, and the genetic features of CTX in Taiwanese have not been examined before. OBJECTIVES: We report a new CTX family with a novel mutation in the CYP27A1 gene and analyze the clinical and molecular genetic features of CTX in Taiwan. METHODS: The clinical and molecular genetic features of the two siblings from the new CTX family and the other 7 reported Taiwanese CTX patients were included for analysis. The clinical features of the enrolled CTX patients were recorded using the indicators that make up the suspicion index (SI). RESULTS: The age at CTX diagnosis of the two siblings in the new CTX family were in late 30s, and predominantly psychiatric features. Both siblings had compound heterozygous splicing mutations in the CYP27A1 gene, including one mutation in exon 2 (c.435G>T, cryptic splice site) and one mutation in intron 7 (c.1264A>G, canonical splice site). None of the CTX patients in Taiwan were diagnosed during childhood or adolescence, and the most common clinical features of the 9 Taiwanese CTX patients were tendinous xanthomas, followed by ataxia and/or spastic paraparesis, dentate nuclei signal alternation at magnetic resonance imaging, intellectual disability and/or psychiatric disturbance, and polyneuropathy. Mutations in the CYP27A1 gene in the Taiwanese population were most commonly observed in exon 2, followed by exon 8 and intron 7. Except for one CTX patient who had an SI score of 100, the SI scores ranged from 300 to 400 before the study of the CYP27A1 gene and diagnosis. CONCLUSIONS: We reported two Taiwanese CTX siblings who had compound heterozygous mutations in CYP27A1. Exons 2 and 8 and intron 7 are the hotspots for Taiwanese CTX mutations. The diagnosis of CTX in Taiwan is usually delayed and is probably under-recognized based on statistical estimations. Early identification and genetic diagnosis may be helpful to CTX patients because early treatment can reduce the accumulation of cholestanol and slow disease progression.

Altered Functional Network Affects Amyloid and Structural Covariance in Alzheimer's Disease.

BACKGROUND: We aimed to investigate how altered intrinsic connectivity networks (ICNs) affect pathologic changes of Alzheimer's disease (AD) at a network-based level. METHODS: Thirty normal controls (NCs), 23 patients with AD-mild cognitive impairment (MCI), and 20 patients with AD-dementia were enrolled. We compared the organization of grey matter structural covariance and functional connectivity in ICNs between NCs and all AD patients who were amyloid ß (Aß)-positive. We further used seed-based interregional covariance analysis to compare structural and Aß plaque covariance in default mode network (DMN) between AD-MCI and AD-dementia groups. RESULTS: The patients with AD had increased functional interregional covariance among the regions of the ICN anchored to dorsal caudate (DC) seeds compared to the NCs. The increased connectivity was associated with extended patterns of reduced Aß plaque covariance in the AD-dementia group compared to the AD-MCI group within the striatal network anchored to DC seeds. Patterns of lower Aß plaque covariance in the AD-dementia group compared to the AD-MCI group were more extended within the network anchored to DC seeds than within the DMN, which was undergoing functional failure in the patients with AD. Significant decreased structural covariance in the AD-dementia group compared to the AD-MCI group was more extended in the DMN during functional failure. CONCLUSIONS: Functional connectivity in ICNs affects the topographic spread of molecular pathologies. The temporal trajectory of pathologic alterations can be well demonstrated by pathologic covariance comparisons between different clinical stages. Pathologic covariance can provide critical support to pathologic interactions at network and molecular levels.