Jen-Hau Chen

Risk Factors for Dementia

Dementia is a complex human disease. The incidence of dementia among the elderly population is rising rapidly worldwide. In the United States, Alzheimers disease (AD) is the leading type of dementia and was the fifth and eighth leading cause of death in women and men aged > or = 65 years, respectively, in 2003. In Taiwan and many other counties, dementia is a hidden health issue because of its underestimation in the elderly population. In Western countries, the prevalence of AD increases from 1-3% among people aged 60-64 years to 35% among those aged > 85 years. In Taiwan, the prevalence of dementia for people aged > or = 65 years was 2-4% by 2000. Therefore, it is important to identify protective and risk factors for dementia to prevent this disease at an early stage. Several factors are related to dementia, e.g. age, ethnicity, sex, genetic factors, physical activity, smoking, drug use, education level, alcohol consumption, body mass index, comorbidity, and environmental factors. In this review, we focus on studies that have evaluated the association between these factors and the risk of dementia, especially AD and vascular dementia. We also suggest future research directions for researchers in dementia-related fields.

Occurrence and Treatment of Suspected Pneumonia in Long-Term Care Residents Dying with Advanced Dementia

Objectives: To describe the occurrence and management of suspected pneumonia in end‐stage dementia and to identify factors associated with aggressiveness of antibiotic treatment.

Lung adenocarcinoma and human papillomavirus infection

Over the past three decades, the incidence of lung adenocarcinoma has increased worldwide. Most individuals with lung adenocarcinoma (especially women) are nonsmokers. Reported risk factors for the development of lung adenocarcinoma include cigarette smoking; exposure to cooking fumes, air pollution, second‐hand smoke, asbestos, and radon; nutritional status; genetic susceptibility; immunologic dysfunction; tuberculosis infection; and asthma. Human papillomavirus (HPV) infection is a known risk factor for the development of squamous cell carcinoma (SCC), but it has not been thoroughly assessed as a potential risk factor for the development of pulmonary adenocarcinoma. More than 50% of people are infected with HPV during their lifetimes, either via intrauterine or postnatal infection. Recent studies involving Taiwanese patients have demonstrated a possible association between HPV infection and the risk of developing pulmonary adenocarcinoma. HPV transmission pathways have not yet been conclusively identified. The observation of certain types of HPV in association with cervical and oral SCC raises the possibility of sexual transmission of HPV from the cervix to the oral cavity, with subsequent transmission to the larynx and then to the lung. HPV infection and metaplasia in lung tissue may increase an individuals susceptibility to the tumorigenesis of pulmonary adenocarcinoma. Further epidemiologic and pathologic investigations will be necessary to establish a causal relation. Cancer 2004.

Potentially inappropriate medications in geriatric outpatients with polypharmacy: application of six sets of published explicit criteria

AIM Our aim was to compare the practicability of six different potentially inappropriate medication (PIM) criteria in geriatric outpatients with polypharmacy. METHODS We analysed baseline data from the Medication Safety Review Clinic in Taiwanese Elders (MSRC-Taiwan) study. The prevalence and correlates of PIMs were determined on the basis of criteria developed in the USA, Canada, France, Norway, Ireland and Thailand. The percentage of PIMs considered as drug-related problems and the problem-solving rate are reported. RESULTS In the 193 participants, the prevalence of PIM varied from 24 to 73%. Application of the criteria revealed that a high number of chronic medications was a common risk factor for having at least one PIM. Of the 1713 medications reviewed, 5.6-14.8% were considered PIMs. Only 30-40% of the identified PIMs were reported as drug-related problems by the MSRC team experts. Criteria with a higher number of statements and a higher percentage of local market/institution drug availability tended to detect more PIMs. CONCLUSIONS The prevalence of PIM varied significantly when different criteria were applied. Caution should be exercised in applying PIM criteria developed in other regions when medication availability in the local market is limited.

Association between air pollutants and dementia risk in the elderly

The aging rate in Taiwan is the second highest in the world. As the population ages quickly, the prevalence of dementia increases rapidly. There are some studies that have explored the association between air pollution and cognitive decline, but the association between air pollution and dementia has not been directly evaluated.

Sequence variants of interleukin 6 (IL-6) are significantly associated with a decreased risk of late-onset Alzheimer's disease.

BACKGROUND In addition to cytotoxic mechanisms directly impacting neurons, β-amyloid (Aβ)-induced glial activation also promotes release of proinflammatory molecules that may self-perpetuate reactive gliosis and damage neighbouring neurons, thus amplifying neuropathological lesions occurring in Alzheimers disease (AD). Palmitoylethanolamide (PEA) has been studied extensively for its anti-inflammatory, analgesic, antiepileptic and neuroprotective effects. PEA is a lipid messenger isolated from mammalian and vegetable tissues that mimics several endocannabinoid-driven actions, even though it does not bind to cannabinoid receptors. Some of its pharmacological properties are considered to be dependent on the expression of peroxisome proliferator-activated receptors-α (PPARα). FINDINGS In the present study, we evaluated the effect of PEA on astrocyte activation and neuronal loss in models of Aβ neurotoxicity. To this purpose, primary rat mixed neuroglial co-cultures and organotypic hippocampal slices were challenged with Aβ1-42 and treated with PEA in the presence or absence of MK886 or GW9662, which are selective PPARα and PPARγ antagonists, respectively. The results indicate that PEA is able to blunt Aβ-induced astrocyte activation and, subsequently, to improve neuronal survival through selective PPARα activation. The data from organotypic cultures confirm that PEA anti-inflammatory properties implicate PPARα mediation and reveal that the reduction of reactive gliosis subsequently induces a marked rebound neuroprotective effect on neurons. CONCLUSIONS In line with our previous observations, the results of this study show that PEA treatment results in decreased numbers of infiltrating astrocytes during Aβ challenge, resulting in significant neuroprotection. PEA could thus represent a promising pharmacological tool because it is able to reduce Aβ-evoked neuroinflammation and attenuate its neurodegenerative consequences.

Medication adherence among geriatric outpatients prescribed multiple medications.

BACKGROUND Poor medication adherence (PMA) is associated with higher risks of morbidity, hospitalization, and mortality. Polypharmacy is not only a determinant of PMA but is also associated with many adverse health outcomes. OBJECTIVE We aimed to determine the prevalence and correlates of PMA in an older population with polypharmacy. METHODS Baseline data from 193 older adults from the Medication Safety Review Clinic Taiwan Study were analyzed. Patients were either prescribed ≥8 long-term medications or visited ≥3 different physicians between August and October 2007. PMA was defined as taking either <80% or >120% of prescribed amounts of a medication. Patients were classified as no (0%), low level (>0 but <25%), and high level (≥25%) PMA depending on what percentage of entire medication regimen taken reached PMA. RESULTS Mean (SD) age was 76 (6) years, and mean number of medications was 9 (3), with a mean medication class number of 4 (1). Of the 1713 medications reviewed, 19% had PMA. However, at patient level, 34%, 32%, and 34% of patients were classified as no, low level, and high level PMA, respectively. Correlates varied by levels of PMA. Compared with patients without PMA, higher medication class number and use of alimentary tract, psychotropic, and hematologic agents were associated with both low and high level PMA. History of dizziness was associated with low level PMA, and higher Mini Mental Status Examination score was associated with high level PMA. CONCLUSIONS To enhance medication adherence in older adults prescribed multiple medications, medication class numbers and certain high-risk medication classes should be taken into account. Physicians should also routinely assess systemic (eg, cognition) or drug-specific characteristics (eg, side effects).

Association Between the Metabolome and Low Bone Mineral Density in Taiwanese Women Determined by 1 H NMR Spectroscopy

Osteoporosis is related to the alteration of specific circulating metabolites. However, previous studies on only a few metabolites inadequately explain the pathogenesis of this complex syndrome. To date, no study has related the metabolome to bone mineral density (BMD), which would provide an overview of metabolism status and may be useful in clinical practice. This cross‐sectional study involved 601 healthy Taiwanese women aged 40 to 55 years recruited from MJ Health Management Institution between 2009 and 2010. Participants were classified according to high (2nd tertile plus 3rd tertile) and low (1st tertile) BMD groups. The plasma metabolome was evaluated by proton nuclear magnetic resonance spectroscopy (1H NMR). Principal components analysis (PCA), partial least‐squares discriminant analysis (PLS‐DA), and logistic regression analysis were used to assess the association between the metabolome and BMD. The high and low BMD groups could be differentiated by PLS‐DA but not PCA in postmenopausal women (Q2 = 0.05, ppermutation = 0.04). Among postmenopausal women, elevated glutamine was significantly associated with low BMD (adjusted odds ratio [AOR] = 5.10); meanwhile, elevated lactate (AOR = 0.55), acetone (AOR = 0.51), lipids (AOR = 0.04), and very low‐density lipoprotein (AOR = 0.49) protected against low BMD. To the best of our knowledge, this study is the first to identify a group of metabolites for characterizing low BMD in postmenopausal women using a 1H NMR–based metabolomic approach. The metabolic profile may be useful for predicting the risk of osteoporosis in postmenopausal women at an early age.

Body mass index (BMI) at an early age and the risk of dementia.

BMI change and BMI at an early age have not been investigated as risks for dementia. This case-control study included 286 dementia patients and 268 controls from two medical centers between 2007 and 2009. BMI information was collected from medical records and questionnaires. Men and women with low BMIs at the time of the study, in their 20s, and in their 40s had significantly increased risks of Alzheimers disease (AD) (odds ratio = OR = 2.62-3.97) and increased vascular dementia (VaD) risk (20s and 40s: OR = 6.23-11.11) compared with those with normal BMIs. High BMI in the 20s and 40s was associated with increased VaD risk (OR = 15.29 and 10.32) among women. For BMI changes from the 20s or 40s, the second and third tertiles were significantly associated with decreased AD risk among women (OR = 0.15-0.35) compared to the first tertile. The third tertile of BMI change from the 20s or 40s was associated with decreased VaD risk among women (OR = 0.06 and 0.14). Low BMIs in the 20s and 40s were stronger predictors of AD and VaD. There was a U-shaped association between BMI at different ages and dementia among participants with VaD.

Genetic polymorphisms of clusterin gene are associated with a decreased risk of Alzheimer’s disease

Clusterin (CLU) is located on chromosome 8p21–p12. The binding of CLU to Ab facilitates Ab clearance and transporting of CLUAb complex. Recent Caucasian genomewide association studies (GWASs) found that CLU rs11136000 is the only SNP consistently associated with a reduced risk of Alzheimer’s disease (AD) [odds ratio (OR) = 0.85–0.86] [1–3], similar findings were observed in two Caucasian candidate-gene studies [4, 5], while the other two Caucasian studies did not observe this association [6, 7]. In contrast, a Chinese study observed an opposite association (OR = 1.39) [8]. This study was aimed to explore the association between CLU polymorphisms and the risk of AD using a set of haplotype-tagging SNPs (htSNPs) in a Taiwanese population. Furthermore, stratified analyses were performed to evaluate how ApoE e4 status and vascular risk factors modified this association. This is a case-control study with a total of 268 AD cases recruited from the Department of Neurology at three teaching hospitals in northern Taiwan from 2007 to 2010. Controls (n = 389) were recruited from the elderly health checkup and volunteers in the hospital during the same period of time. All study participants were Taiwanese aged 60 and older. A well-trained personnel administered questionnaires to obtain detailed information on demography, lifestyle, and comorbidity. Neurologists used MiniMental State Examination and Clinical Dementia Rating to assess the cognitive function of AD patients. Diagnosis of AD was made by using Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) and the criteria of