Cholinesterase Inhibitor Donepezil Increases Mitochondrial Biogenesis through AMP-Activated Protein Kinase in the Hippocampus.

OBJECTIVE: Donepezil, a widely prescribed drug for Alzheimer's disease (AD), is now considered to have multimodal actions beyond cholinesterase inhibition. We aimed to see whether donepezil enhances mitochondrial biogenesis and relevant signaling pathways since mitochondrial dysfunction is a key feature of the hypometabolic AD brain. METHODS: As a metabolic gauge, AMP-activated protein kinase (AMPK) was investigated as a tentative mediator of neurometabolic action of donepezil. Changes in phospho-AMPK levels, mitochondrial biogenesis, and ATP levels were measured upon donepezil treatment using neuroblastoma cells, primary cultured neurons and ex vivo hippocampal tissue of adult mice. RESULTS: Donepezil dose-dependently increased mitochondrial biogenesis and ATP levels as well as expression of PGC-1α and NRF-1 in neuroblastoma cells. Donepezil dose-dependently activated AMPK; however, inhibition of AMPK abolished the observed effects of donepezil, indicating that AMPK is a key mediator of donepezil's action. Notably, mitochondrial biogenesis upon donepezil treatment was mainly observed within dendritic regions of primary cultured hippocampal neurons. Levels of synaptic markers were also increased by donepezil. Finally, AMPK- dependent mitochondrial biogenesis by donepezil was confirmed in organotypic hippocampal tissue. CONCLUSIONS: Our findings indicate that AMPK/PGC-1α signaling is involved in beneficial actions of donepezil on neurometabolism. Pharmacological activation of AMPK might be a promising approach to counteract AD pathogenesis associated with brain hypometabolism.

Frontal Lobe Function and Risk of Hip Fracture in Patient With Alzheimer Disease: An Analysis of Linked Data.

To determine the association between frontal lobe function and risk of hip fracture in patients with Alzheimer disease (AD).Retrospective cohort study using multicenter hospital-based dementia registry and national health insurance claim data was done. Participants who had available data of neuropsychological test, national health insurance claim, and other covariates were included. A total of 1660 patients with AD were included based on Stroop Test results. A total of 1563 patients with AD were included based on the Controlled Oral Word Association Test (COWAT) results. Hip fracture was measured by validated identification criteria using national health insurance claim data. Frontal lobe function was measured by Stroop Test and COWAT at baseline.After adjusting for potential covariates, including cognitive function in other domains (language, verbal and nonverbal memory, and attention), the Cox proportional hazard regression analysis revealed that risk of a hip fracture was decreased with a hazard ratio (HR) of 0.98 per one point of increase in the Stroop Test (adjusted HR = 0.98, 95% confidence interval [CI]: 0.97-1.00) and 0.93 per one point increase in COWAT (adjusted HR = 0.93, 95% CI: 0.88-0.99).The risk of hip fracture in AD patients was associated with baseline frontal lobe function. The result of this research presents evidence of association between frontal lobe function and risk of hip fracture in patients with AD.

Participation in Physical, Social, and Religious Activity and Risk of Depression in the Elderly: A Community-Based Three-Year Longitudinal Study in Korea.

BACKGROUND: We examined the longitudinal association between participation in individual or combinations of physical, social, and religious activity and risk of depression in the elderly. METHODS: Elderly subjects aged ≥ 60 years who completed the Living Profiles of Older People Survey in Korea (n = 6,647) were included. The baseline assessment, Wave 1, was conducted in 2008, and a follow-up assessment, Wave 2, was conducted in 2011. We defined participation in frequent physical activity as ≥ 3 times weekly (at least 30 minutes per activity). Frequent participation in social and religious activity was defined as ≥ 1 activity weekly. The primary outcome was depression at 3-year follow up. RESULTS: Multivariable logistic regression analysis showed that subjects who participated in frequent physical, social, and religious activity had an adjusted odds ratio of 0.81 (95% confidence interval [CI], 0.69-0.96), 0.87 (95% CI, 0.75-1.00), and 0.78 (95% CI, 0.67-0.90), respectively, compared with participants who did not participate in each activity. Participants who participated in only one type of activity frequently and participants who participated in two or three types of activities frequently had an adjusted odds ratio of 0.86 (95% CI, 0.75-0.98) and 0.64 (95% CI, 0.52-0.79), respectively, compared with participants who did not participate in any type of physical, social, and religious activity frequently. CONCLUSION: Participation in physical, social, and religious activity was associated with decreased risk of depression in the elderly. In addition, risk of depression was much lower in the elderly people who participated in two or three of the above-mentioned types of activity than that in the elderly who did not.

Increased plasma levels of heat shock protein 70 associated with subsequent clinical conversion to mild cognitive impairment in cognitively healthy elderly.

BACKGROUND AND AIMS: Heat shock proteins (HSPs) have been regarded as cytoprotectants that protect brain cells during the progression of neurodegenerative diseases and from damage resulting from cerebral ischemia. In this study, we assessed the association between plasma HSP 70/27 levels and cognitive decline. METHODS: Among participants in the community-based cohort study of dementia called the Gwangju Dementia and Mild Cognitive Impairment Study, subjects without cognitive impairment at baseline, who then either remained without impairment (non-conversion group), or suffered mild cognitive impairment (MCI) (conversion group) (non-conversion group, N = 36; conversion group, N = 30) were analyzed. RESULTS: After a five to six year follow-up period, comparison of the plasma HSP 70 and HSP 27 levels of the two groups revealed that only the plasma HSP 70 level was associated with a conversion to MCI after adjustments for age, gender, years of education, follow-up duration, APOE e4, hypertension, and diabetes (repeated measure analysis of variance: F = 7.59, p = 0.008). Furthermore, an increase in plasma HSP 70 level was associated with cognitive decline in language and executive function (linear mixed model: Korean Boston Naming Test, -0.426 [-0.781, -0.071], p = 0.019; Controlled Oral Word Association Test, -0.176 [-0.328, -0.023], p = 0.024; Stroop Test, -0.304 [-0.458, -0.150], p<0.001). CONCLUSIONS: These findings suggest that the plasma HSP 70 level may be related to cognitive decline in the elderly.

Effect of hypertension on the resting-state functional connectivity in patients with Alzheimer's disease (AD).

BACKGROUND/OBJECTIVES: Although hypertension is known to be a risk factor for AD, the effects of hypertension on brain function in AD patients are not well understood. We investigated alterations in resting-state functional connectivity according to the presence of hypertension in AD patients by using a method of correlation analysis based on a seed region in the posterior cingulate cortex (PCC). We also determined whether differences in resting-state connectivity were associated with gray matter atrophy. METHODS: Thirty-seven AD patients (18 patients with hypertension and 19 patients without hypertension) underwent the resting-state functional magnetic resonance imaging. We obtained the PCC maps by a temporal correlation method, to identify alterations in the functional connectivity of the PCC in hypertensive group relative to non-hypertensive group. Voxel-based morphometry analysis was also applied to adjust the confounding effect of gray matter atrophy. RESULTS: We detected a decreased connectivity to the PCC in the regions of subgenual anterior cingulated cortex (ACC) in hypertensive group relative to non-hypertensive group. However, we observed a pattern of increased connectivity between the PCC and the left inferior parietal cortex in hypertensive group. After correction for gray matter atrophy, all detected regions still remained significant. CONCLUSIONS: Altered connectivity in AD patients with hypertension suggests the possibility that hypertension impairs resting-state functional connectivity of the AD brain, inducing a compensational process outside the impaired networks or disequilibrium in brain connectivity. This finding may account for an additional contribution of hypertension to the pathophysiology of AD.

Effects of a multidomain lifestyle modification on cognitive function in older adults: an eighteen-month community-based cluster randomized controlled trial.

BACKGROUND: A healthy lifestyle may protect against cognitive decline. We examined outcomes in elderly individuals after 18 months of a five-group intervention program consisting of various modalities to prevent cognitive decline. METHODS: We conducted a cluster randomized controlled trial assessing 460 community-dwelling individuals aged 60 years and older in a geriatric community mental health center in Suwon, Republic of Korea, between 2008 and 2010. We developed an intervention program based on the principles of contingency management, which could be delivered by ordinary primary health workers. Group A (n = 81) received standard care services. Group B (n = 80) received bimonthly (once every 2 months) telephonic care management. Group C (n = 111) received monthly telephonic care management and educational materials similar to those in group B. Group D (n = 93) received bimonthly health worker-initiated visits and counseling. Group E (n = 94) received bimonthly health worker-initiated visits, counseling, and rewards for adherence to the program. RESULTS: The primary outcome was the change in Mini-Mental State Examination (MMSE) scores from baseline to the final follow-up visit at 18 months. Group E showed superior cognitive function to group A (adjusted coefficient ß = 0.99, p = 0.044), with participation in cognitive activities being the most important determining factor among several health behaviors (adjusted coefficient ß = 1.04, p < 0.01). CONCLUSIONS: Engaging in cognitive activities, in combination with positive health behaviors, may be most beneficial in preserving cognitive abilities in community-dwelling older adults.

A normative study of lexical verbal fluency in an educationally-diverse elderly population.

OBJECTIVE: Lexical fluency tests are frequently used to assess language and executive function in clinical practice. We investigated the influences of age, gender, and education on lexical verbal fluency in an educationally-diverse, elderly Korean population and provided its' normative information. METHODS: We administered the lexical verbal fluency test (LVFT) to 1676 community-dwelling, cognitively normal subjects aged 60 years or over. RESULTS: In a stepwise linear regression analysis, education (B=0.40, SE=0.02, standardized B=0.506) and age (B=-0.10, SE=0.01, standardized B=-0.15) had significant effects on LVFT scores (p<0.001), but gender did not (B=0.40, SE=0.02, standardized B=0.506, p>0.05). Education explained 28.5% of the total variance in LVFT scores, which was much larger than the variance explained by age (5.42%). Accordingly, we presented normative data of the LVFT stratified by age (60-69, 70-74, 75-79, and ≥80 years) and education (0-3, 4-6, 7-9, 10-12, and ≥13 years). CONCLUSION: The LVFT norms should provide clinically useful data for evaluating elderly people and help improve the interpretation of verbal fluency tasks and allow for greater diagnostic accuracy.

Association between white matter hyperintensity severity and cognitive impairment according to the presence of the apolipoprotein E (APOE) ε4 allele in the elderly: retrospective analysis of data from the CREDOS study.

OBJECTIVE: To investigate the effect of white matter hyperintensity (WMH) severity on cognitive function according to presence of the apolipoprotein E (APOE) ε4 allele. METHOD: From participants in a nationwide, multicenter, hospital-based cohort study of dementia by the Clinical Research Center for Dementia of South Korea (November 2005 to December 2011), data for 5,077 elderly subjects (mean [SD] age = 71.37 [8.40] years) who had available data for APOE genotype and WMH severity were studied retrospectively. We used the diagnostic criteria for mild cognitive impairment proposed by Petersen et al; the diagnostic criteria for vascular dementia included in DSM-IV; and, for probable Alzheimer's disease, the criteria issued by the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association. WMH severity was evaluated using modified criteria of Fazekas et al and Scheltens et al using T2 axial or fluid-attenuated inversion recovery magnetic resonance images, yielding 3 groups for WMH severity level. APOE genotype was determined by analysis of venous blood, and all participants were classified into 2 groups depending on presence or absence of the APOE ε4 allele. The Seoul Neuropsychological Screening Battery-Dementia Version was used for all subjects. Cognitive impairment, classified by 6 cognitive test scores, was the primary outcome measure. Using multiple logistic regression, we investigated which cognitive domains were associated with WMH severity and the APOE ε4 allele, and, using analysis of covariance, we examined the interaction effects of these 2 factors on cognitive test scores. RESULTS: After multivariable adjustments, logistic regression analyses showed that WMH severity was associated with higher odds of cognitive impairment on frontal/executive function tests in both APOE ε4 carriers (odds ratio [OR] = 2.49; 95% CI, 1.65-3.76) and noncarriers (OR = 2.36; 95% CI, 1.83-3.03). WMH severity was not significantly associated with memory function in APOE ε4 carriers: for verbal memory, ε4 noncarriers had an OR of 1.44 (95% CI, 1.13-1.84), and ε4 carriers had an OR of 1.36 (95% CI, 0.87-2.04); for visuospatial memory, ε4 noncarriers had an OR of 1.86 (95% CI, 1.45-2.37), and ε4 carriers had an OR of 1.35 (95% CI, 0.89-2.04). Moreover, a significant interaction effect between APOE ε4 and WMH severity was confirmed on memory tests by analysis of covariance (verbal memory: F = 3.40, P = .033; visuospatial memory: F = 8.49, P < .001). CONCLUSIONS: Severe WMHs appear to be predominantly associated with frontal/executive dysfunction, irrespective of APOE ε4 allele presence. WMH severity and APOE ε4 had an interactive effect on memory function, with WMH severity affecting memory impairment only in APOE ε4 noncarriers.

The effects of head circumference (HC) and lifetime alcohol consumption (AC) on cognitive function in the elderly.

Smaller premorbid brain volume is known to be related to cognitive deterioration in older adults, supporting a reserve hypothesis of brain aging. Heavy lifetime alcohol consumption (AC) may also increase the risk of cognitive impairment. The aim of this study was to examine the effects of head circumference (HC) and lifetime AC on cognitive function in the elderly. This study is part of a large, longitudinal study of men aged 60 years or older in the Korean community. We studied 1569 subjects with complete demographic, anthropometric and AC data. Cognitive function was assessed by the Korean version of Mini Mental State Examination (K-MMSE). Participants reported at the time of interview their lifetime alcohol drinking patterns. HC was also measured. We did a cross-sectional analysis the relation between two factors to cognitive function. After a multivariable adjustment, the interactive effect between HC and lifetime AC was shown to be significantly associated with cognitive function (F=2.55, p=0.038). Simple main effect analysis showed that smaller HC and a high level of lifetime AC were related with decreased cognitive function. All these findings suggest the possibility that lifetime AC and HC have synergistic effects on cognitive impairment.

The effect of anemia and white matter hyperintensities (WMH) on cognitive impairment in patients with amnestic mild cognitive impairment (MCI).

Anemia and subcortical ischemic change might be associated with increased risks for cognitive impairment among the elderly. This study examined the associations among anemia, WMH and cognitive function in patients with amnestic MCI. We recruited 278 subjects with amnestic MCI from the Clinical Research Center for Dementia of South Korea (CREDOS), a hospital-based cohort study. A standardized neuropsychological battery, containing tests of language, visuospatial function, verbal memory and executive function, was used for all patients. Anemia was defined as a hemoglobin concentration below 12 g/dl for women and below 13 g/dl for men. The severity of WMH was also examined using brain magnetic resonance imaging (MRI). After multivariable adjustments, anemia and WMH were associated with poorer performance on cognitive function tests (anemia: Stroop test, F=4.17, p=0.042; WMH: Stroop test, F=6.45, p=0.002; Rey-complex figure test-copy, F=4.08, p=0.018). Moreover, a significant interaction between anemia and the severity of WMH was observed in performance on the Go/no go test (F=4.50, p=0.012) and the Stroop test (F=3.36, p=0.037). In post hoc analysis, anemic patients with severe WMH had significantly worse scores on measure of executive function (Go/no go test, p=0.011; Stroop test, p=0.001). Anemia and WMH had interactive effects on executive function impairment among the elderly with amnestic MCI.

AMPK γ2 subunit gene PRKAG2 polymorphism associated with cognitive impairment as well as diabetes in old age.

Metabolic and cognitive disorders are closely related. However, the molecular mechanism underlying this association is still elusive. Given the importance of energy metabolism in neuronal cells, AMP-activated protein kinase (AMPK), a master switch of energy metabolism, could be an independent factor affecting cognitive as well as metabolic functions. Therefore, we examined the relationship between the AMPK γ2 gene, the PRKAG2 -26C/T polymorphism and cognitive impairment or diabetes in 1609 subjects aged from 60 to 80. We performed multivariate logistic regression analyses with adjustment for age, gender, education, smoking, alcohol, depression, waist circumference, APOE e4, and stroke history. We found a significant association between the -26C/T polymorphism (CC vs. CT/TT) and cognitive impairment (OR, 1.6; 95% CI, 1.1-2.3). Moreover, this polymorphism (CC/CT vs. TT) was also related to the presence of diabetes (OR, 1.8; 95% CI, 1.2-2.8). Importantly, the relationship with cognitive impairment was still significant in non-diabetic individuals (OR, 1.6; 95% CI, 1.1-2.4). Further analyses with a subpopulation (n=611) revealed that CC homozygotes relative to T-allele carriers had significantly better performances in verbal memory and attentional tasks. These findings collectively support a hypothesis that AMPK has a role not only in metabolic functioning but also in cognitive functioning in humans. Extended longitudinal study with a larger number of samples is warranted.

Anemia associated with depressive symptoms in mild cognitive impairment with severe white matter hyperintensities.

Depression with mild cognitive impairment (MCI) may be associated with a high risk of dementia. Likewise, anemia and subcortical ischemic changes might be associated with depression in the elderly individuals. We examined the relationship between anemia, subcortical ischemic changes, and depressive symptoms in 388 elderly patients with MCI (74.0% women, mean age = 71.8) who were evaluated at the Clinical Research Center for Dementia of South Korea. Blood samples were drawn from all consenting participants and depressive symptoms were assessed using the 15-item Geriatric Depression Scale (GDS-15). We also evaluated the severity of white matter hyperintensities (WMH) on brain using magnetic resonance imaging (MRI). After a multivariable adjustment, we found no significant differences in GDS-15 score between anemic and nonanemic groups (F = 3.0, P = .085) and among WMH level groups (F = 0.6, P = .574) independently. However, the interaction between anemia and the severity of WMH was significantly associated with depressive symptoms (analysis of covariance, F = 7.8, P < .001). In post hoc tests, a higher depressive symptom score was observed in anemic participants with severe WMH. Anemia with severe subcortical ischemic changes appears to be related to depressive symptoms in patients with MCI.

Application of health concern and activity model on cognition in the elderly.

The aim of this study was to examine the effects of physical, mental, social activity, and health concern on cognition in the elderly by means of the health concern and activity (HCA) model. Data were obtained from 3157 subjects aged 60 years and above. The subjects were divided into four groups according to the HCA model. Cognitive function was assessed by the Korean version of the mini-mental state examination (K-MMSE). A cross-sectional, factorial design was used in which the K-MMSE score was the dependent variable, with physical, mental, and social activity as one factor and health concern as the other. Analysis of covariance revealed significant differences in the K-MMSE score between all four groups after adjusting for age, sex, education, current smoking, and alcohol consumption for all subjects. The results suggest that having health concerns as well as physical, mental, or social activity is associated with cognitive function in the elderly.

Effects of head circumference and metabolic syndrome on cognitive decline.

BACKGROUND: Brain volume progressively decreases with an increase in atrophy, and the brain becomes more susceptible to degenerative brain diseases such as Alzheimer's disease. Metabolic syndrome has also been associated with an increased risk of cognitive decline in the elderly. AIMS: In this study, we aimed to examine the effects of head circumference and metabolic syndrome on cognitive decline. METHODS: This study was part of a longitudinal study conducted on Koreans aged 60 years or older. We analyzed a final sample of 596 Korean participants with complete baseline and 2-year follow-up data. The cognitive function of the subjects was assessed using the Korean version of the Mini Mental State Examination (MMSE). Head circumference was measured from the glabella to the occipital protuberance using a measuring tape. Metabolic syndrome was defined according to the NCEP-ATP III standards. Central obesity was assessed on the basis of waist-circumference values, in accordance with the World Health Organization Western Pacific Region report on Asians. We used a longitudinal factorial design in which the MMSE score was the dependent variable, and head circumference and metabolic syndrome were considered as factors. RESULTS: After adjusting the results for age, gender, education, height, weight, baseline MMSE, and number of follow-up years, we observed that smaller head circumference and the presence of metabolic syndrome were independently associated with rapid cognitive decline. CONCLUSION: All these findings suggest that smaller head circumference and the presence of metabolic syndrome have additive effects on cognitive decline.

Determinants of length of stay for psychiatric inpatients: analysis of a national database covering the entire Korean elderly population.

OBJECTIVE: In a rapidly aging society, inappropriately long geropsychiatric inpatient hospitalization is a challenging concern for mental health policy-makers and researchers. This study aimed to investigate patient and institutional factors affecting geropsychiatric inpatient length of stay (LOS), providing an overview of current geropsychiatric health care system in South Korea. METHODS: This retrospective, population-based, cross-sectional study analysed nationwide reimbursement claim databases covering the entire elderly population of Korea between January 2005 and June 2006. Given the nested structure of the data, a multivariate multilevel regression analysis was performed. RESULTS: The average LOS was 128 days. Males, patients with schizophrenia, and those enrolled in a National Medical Care Aid program tended to have longer hospital stays. Patient age was negatively related to LOS. Institutional variables related to longer hospitalizations included a psychiatric hospital, a higher number of beds, fewer human resource employees, a higher proportion of male, oldest old, and patients with dementia. CONCLUSIONS: Our results suggest that policies targeting geropsychiatric patients diagnosed with schizophrenia, enrolled in National Medical Care Aid programs, and admitted to psychiatric hospitals could reduce LOS. Additionally, the impact of the patient composition of a medical institution on LOS needs to be closely investigated.

Cognitive decline is associated with nutritional risk in subjects with small head circumference (HC).

Nutrition has been found to be associated with cognitive impairment, but it has not been established whether these associations are present solely in later life or whether they are present in younger age as well. HC is a good indicator of brain development and the most sensitive anthropometric indicator of prolonged malnutrition during early life. This study examined the interaction between early HC and later (nutrition screening initiative) nutritional factors on the risk of cognitive decline in the elderly. The longitudinal factorial design had the mini-mental state examination (MMSE) score as the dependent variable, with HC as one factor and nutritional risk as another. We studied a sample of 495 not cognitively impaired Korean participants with 2 years follow-up data. After multivariable adjustment, interactive effect between HC and nutritional risk was significantly associated with cognitive decline (F=2.449, p=0.045). Simple main effect analysis showed that compared with highest HC, lowest HC was associated with a cognitive decline. Nutritional risk was associated with cognitive function decline only in individuals with small HC. Therefore, the prevention for cognitive impairment and dementia should involve nutritional strategies throughout life.

Relationship between the diagnostic components of metabolic syndrome (MS) and cognition by ApoE genotype in the elderly.

The purpose of this study was to find out the effect of the ApoE genotype on the relationship between metabolic syndrome (MS) and its diagnostic components and cognitive impairment in the elderly. A total of 2944 subjects aged over 60 years were analyzed from the data of Gwangju Dementia and Mild Cognitive Impairment Study. We examined demographic characteristics, current and past illness history, drug history, Korean version-mini-mental state examination (K-MMSE). We also examined ApoE genotype and analyzed associated factors with MS. The MS was present in 53.8% of the subjects (36.8% of men and 61.1% of women). On multiple logistic regression analysis, MS was not associated with the cognitive impairment (K-MMSE score <18) adjusted for age, sex, and educational level. The interactive effect between systolic and diastolic blood pressure (SBP, and DBP, respectively) and ApoE on cognition was not significant (all p>0.3), but the interactive effect between triglyceride (TG), high-density-lipoprotein-cholesterol (HDLc) and ApoE on cognition was significant after adjustment for age, sex, and education (B=-0.285, Wald=4.194, p=0.041; B=0.372, Wald=4.134, p=0.042). These results suggest that blood TG and HDLc may affect cognitive function in the elderly in the presence of ApoE varepsilon4 allele.

Peripheral cytokines and chemokines in Alzheimer's disease.

A chronic inflammatory process has been implicated in the neuropathology of Alzheimer's disease (AD). The present review focuses on the current knowledge of circulating serum and plasma biomarkers of AD that are linked to inflammatory reactions. There is abundant evidence that inflammatory mechanisms within the central nervous system contribute to cognitive impairment via cytokine-mediated interactions between neurons and glial cells. Interleukins 1, 4, 6, 10, 12, 16, and 18, tumour necrosis factor, and several chemokines have been suggested as biomarkers of AD. Nonetheless, data on circulating cytokine levels are somewhat inconsistent with regard to peripheral cytokine dysregulation in AD. In summary, definite statements concerning differences in inflammatory biomarkers between controls and AD patients will require the use of sensitive multiplex assays in large patient groups in conjunction with measures of disease severity.

Simultaneous measurement of 23 plasma cytokines in late-life depression.

According to the cytokine hypothesis of depression, cytokines play key roles in the behavioral, neuroendocrinal, and neurochemical features of depression. In this study, we used a bioplex assay to simultaneously measure the levels of 23 plasma cytokines in 18 patients with late-life depression and 38 normal controls, and these levels were compared between the two groups. The plasma interleukin-1alpha (IL-1alpha) levels were found to be significantly different between the two groups. After adjusting for age, gender, low-density lipoprotein cholesterol, and triglyceride, the plasma IL-1alpha levels were significantly higher in the patients with late-life depression than in the normal control subjects. Thus, this study provides preliminary evidence that plasma IL-1alpha may play important roles in the pathogenesis of late-life depression.