Group Music Intervention Using Percussion Instruments to Reduce Anxiety Among Elderly Male Veterans with Alzheimer Disease.

BACKGROUND This study aimed to assess the impact of a group music intervention on anxiety and depression of elderly male veterans with dementia. MATERIAL AND METHODS In total, 50 elderly men with Alzheimer disease were randomly divided into intervention and control groups. Patients in the intervention group attended a 60-minute group music session that used percussion instruments with familiar music in the morning once a week for 12 weeks, whereas those in the control group received a rest and reading session at the same intervals and under the same conditions. The Hamilton Anxiety Rating Scale and Geriatric Depression Scale were used to assess anxiety and depression at baseline, week 6, and week 12. The Primary Measures of Music Audiation (PMMA) was used to assess musical aptitude at the baseline. RESULTS A significant reduction in the anxiety level following the 12-week music sessions was observed in the intervention group (P<.001), but there was no significant change in the control group. However, the change in depressive symptoms between the 2 groups was nonsignificant. In the intervention group, when stratifying patients based on music aptitude determined through PMMA assessment, patients with high PMMA scores had significantly reduced anxiety symptoms over time compared with those with low scores. CONCLUSIONS For elderly male veterans with dementia, participating in a group music intervention reduced anxiety symptoms. In patients with high musical aptitude, the treatment effects on anxiety reduction were satisfactory. Measures of music aptitude may provide valuable information regarding patients' response to music intervention.

High-Frequency External Muscle Stimulation Reduces Depressive Symptoms in Older Male Veterans: A Pilot Study.

OBJECTIVE: Late-life depression (LLD) is a severe public health problem. Given that pharmacological treatments for LLD are limited by their side effects, development of efficient and tolerable nonpharmacological treatment for LLD is urgently required. This study investigated whether high-frequency external muscle stimulation could reduce depressive symptoms in LLD. METHODS: Twenty-two older male veterans with major depression were recruited and randomized into a treatment (n = 9) or sham control group (n = 13). The groups received high-frequency external muscle stimulation or sham intervention 3 times per week for 12 weeks. Clinical symptoms and muscle strength were evaluated at baseline and every 2 weeks. RESULTS: The 2 groups were homogeneous in age, baseline clinical symptoms, and muscle strength. The treatment group showed significant improvement in depression and anxiety scores and muscle strength (all P < .01), whereas the control group showed no significant change after the 12-week follow-up. Compared to the control group, the treatment group showed significant improvements in depression (Geriatric Depression Scale, P = .009; Hamilton Depression Rating Scale, P = .007) and anxiety scores (HAMA, P = .008) and muscle strength (all P < .001). Changes in depression and anxiety levels were significantly correlated with changes in muscle strength after the study. In the treatment group, we observed a trend of correlation between the reduction in depression and muscle strength gains. CONCLUSION: High-frequency external muscle stimulation appears to be an effective treatment for older patients with LLD. Large studies with more tests and/or conducted in different populations are warranted to validate these preliminary findings.

MCP-2/CCL8 Level Associated With Suicidal Ideation in Elderly Men With Major Depression.

OBJECTIVES: We compared serum levels of chemokines between male elders with major depressive disorder (MDD) and healthy controls, verifying whether any difference exists in the levels of these mediators between those with and without current suicidal ideation (SI). METHODS: We enrolled 145 male elders aged 65 or older and analyzed 40 chemokines in patients with MDD with SI (n = 24) and without SI (n = 23), as well as healthy controls (n = 98). RESULTS: The patients with MDD with SI presented higher levels of MCP-2/CCL8 (p < 0.001) compared with the patients with MDD without SI and the healthy controls. CONCLUSIONS: Current findings suggest a potential role of MCP-2/CCL8 in suicidality among elderly males with depression.

Association of depression and loneliness with specific cognitive performance in non-demented elderly males.

BACKGROUND: Loneliness and depression are very common in the aged population. Both have negative impacts on cognition in the elderly. The present study aimed to investigate the effect of loneliness and depression on total as well as specific cognitive domains in cognitively normal male subjects. MATERIAL/METHODS: A total of 189 cognitively normal male subjects were recruited and underwent Cognitive Abilities Screening Instrument (CASI) and Wechsler Digit Span Task tests. Depression was assessed by the Geriatric Depression Scale-Short Form (GDS-SF) and loneliness by UCLA loneliness scales. Partial correlation test was used to explore the correlation between loneliness/depression and total as well as specific cognition function, with the controlled factors of age and education. RESULTS: Both depression and loneliness are negatively correlated with global cognitive function as evaluated with CASI (r=-0.227, p=0.002; r=-0.214, p=0.003, respectively). The domains of Attention, Orientation, Abstraction and judgment, and List-generating fluency of cognitive function were specifically associated with loneliness, and the domain of orientation was associated with depression after controlling the factors age and years of education. CONCLUSIONS: Our findings suggest that loneliness and depression may have negative impacts on global and specific domains of cognitive function in non-demented elderly males. Both loneliness and depression should be actively recognized earlier and appropriately treated because they are significant sources of cognitive impairment in the elderly.

Functional Connectivity Density Mapping of Depressive Symptoms and Loneliness in Non-Demented Elderly Male.

BACKGROUND: Depression and loneliness are prevalent and highly correlated phenomena among the elderly and influence both physical and mental health. Brain functional connectivity changes associated with depressive symptoms and loneliness are not fully understood. METHODS: A cross-sectional functional MRI study was conducted among 85 non-demented male elders. Geriatric depression scale-short form (GDS) and loneliness scale were used to evaluate the severity of depressive symptoms and loneliness, respectively. Whole brain voxel-wise resting-state functional connectivity density (FCD) mapping was performed to delineate short-range FCD (SFCD) and long-range FCD (LFCD). Regional correlations between depressive symptoms or loneliness and SFCD or LFCD were examined using general linear model (GLM), with age incorporated as a covariate and depressive symptoms and loneliness as predictors. RESULTS: Positive correlations between depressive symptoms and LFCD were observed in left rectal gyrus, left superior frontal gyrus, right supraorbital gyrus, and left inferior temporal gyrus. Positive correlations between depressive symptoms and SFCD were observed in left middle frontal gyrus, left superior frontal gyrus, bilateral superior medial frontal gyrus, left inferior temporal gyrus, and left middle occipital region. Positive correlations between SFCD and loneliness were centered over bilateral lingual gyrus. CONCLUSION: Depressive symptoms are associated with FCD changes over frontal and temporal regions, which may involve the cognitive control, affective regulation, and default mode networks. Loneliness is associated with FCD changes in bilateral lingual gyri that are known to be important in social cognition. Depressive symptoms and loneliness may be associated with different brain regions in non-demented elderly male.

APOE ɛ4 polymorphism and cognitive deficit among the very old Chinese veteran men without dementia.

Apolipoprotein E (APOE) gene polymorphism has been reported to be associated with cognitive dysfunction in healthy individuals, however the results were controversial in the very old elderly. The aim of this study is to assess the possible association of the APOE polymorphism with cognitive dysfunction in people aged 75 years and over. Four hundred and twenty-five aged Chinese veteran men without dementia were enrolled for APOE genotyping and neuropsychological tests including Mini-Mental Status Examination (MMSE), Digit Span Forward and Backward, and Cognitive Ability Screening Instrument Chinese language version (CASI C-2.0) were evaluated in these subjects. Among the elderly veterans, people who carry APOE ɛ4 were found to have worse performance on the total CASI scores, the abstraction/judgment subscores and the list-generating fluency subscores. This study suggests that the APOE ɛ4 alleles contributed detrimental effects on cognitive function in the very old veterans who do not have dementia.

Catechol-O-methyltransferase Val158Met polymorphism on the relationship between white matter hyperintensity and cognition in healthy people.

BACKGROUND: White matter lesions can be easily observed on T2-weighted MR images, and are termed white matter hyperintensities (WMH). Their presence may be correlated with cognitive impairment; however, the relationship between regional WMH volume and catechol-O-methyltransferase (COMT) Val158Met polymorphism in healthy populations remains unclear. METHODS: We recruited 315 ethnic Chinese adults with a mean age of 54.9 ± 21.8 years (range: 21-89 y) to examine the genetic effect of COMT on regional WMH and the manner in which they interact to affect cognitive function in a healthy adult population. Cognitive tests, structural MRI scans, and genotyping of COMT were conducted for each participant. RESULTS: Negative correlations between the Digit Span Forward (DSF) score and frontal WMH volumes (r = -.123, P = .032, uncorrected) were noted. For the genetic effect of COMT, no significant difference in cognitive performance was observed among 3 genotypic groups. However, differences in WMH volumes over the subcortical region (P = .016, uncorrected), whole brain (P = .047, uncorrected), and a trend over the frontal region (P = .050, uncorrected) were observed among 3 COMT genotypic groups. Met homozygotes and Met/Val heterozygotes exhibited larger WMH volumes in these brain regions than the Val homozygotes. Furthermore, a correlation between the DSF and regional WMH volume was observed only in Met homozygotes. The effect size (cohen's f) revealed a small effect. CONCLUSIONS: The results indicate that COMT might modulate WMH volumes and the effects of WMH on cognition.

Interleukin-1 beta C-511T polymorphism modulates functional connectivity of anterior midcingulate cortex in non-demented elderly Han males.

Recent resting fMRI studies have suggested that the functional connectivity of the brain's large-scale networks is associated with the cognitive decline of aging and is modulated by genetic factors. Our previous study found a significant association between interleukin-1 (IL-1 beta) C-511T polymorphism and working memory performance among elderly people. This study investigates the effects of IL-1 beta C-511T polymorphism on the functional connectivity of the cognitive division of the cingulate cortex [i.e., the anterior midcingulate (aMCC)] in non-demented Han elderly people and tests the hypothesis that T/T carriers are associated with lowered FC. Non-demented elderly males (n = 95) received resting MRI scanning, genotyping, and cognitive evaluation using the cognitive abilities screening instrument (CASI) and the Wechsler digit span task test. The functional connectivity map in each subject was derived based on positive correlations of low-frequency fMRI fluctuations with a seed in the aMCC according to structural definition. Between-group difference was compared by random effect analysis. Compared to the C/C or C/T carriers, the T/T carriers had a significantly worse CASI performance, especially in the abstraction scores. For the functional connectivity analysis, the T/T carriers exhibited significantly lower functional connectivity with several prefrontal areas and the left putamen. The cortico-striatal connection between the aMCC and left putamen was correlated with the CASI abstraction and attention scores. The results were consistent with our hypothesis and supported that the brains' functional connectivity in elderly people may be modulated by genetic polymorphism associated with local inflammation processes.

Effect of the BDNF Val66Met polymorphism on regional gray matter volumes and cognitive function in the Chinese population.

The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism is common and influences the activity-dependent secretion of BDNF, which is critical for neuronal plasticity and survival. This study investigated the genetic effect of the BDNF Val66Met polymorphism on cognitive function and regional gray matter (GM) volume in a healthy Chinese population (n = 330). Voxel-based morphometry (VBM)-optimized analysis was used. There was no significant difference in the neuropsychological performances among the three BDNF genotypic groups. VBM analyses demonstrated that Met homozygotes had greater GM volumes than Val homozygotes in the left medial frontal gyrus, the left middle temporal gyrus, the left cerebellum, and the right middle temporal gyrus, and had larger GM volumes than Val/Met heterozygotes in the left middle temporal gyrus, the left inferior temporal gyrus, and the right superior frontal gyrus. Our findings suggest that the presence of two Met alleles has a protective effect on regional GM volumes in the Chinese population.

Interleukin-1 alpha (rs1800587) genetic polymorphism is associated with specific cognitive functions but not depression or loneliness in elderly males without dementia.

Inflammatory process is considered to be a pathway that results in neurodegeneration, and numerous plasma cytokines have been examined for their association with cognitive function and depression. Interleukin-1 alpha (IL-1A) genetic polymorphism (rs1800587) has been found to be associated with Alzheimer's disease susceptibility. The aim of this study was to investigate the effect of IL-1A rs1800587 genetic effects on cognitive functions, loneliness and depression severity in elderly males without dementia or major depression. 192 non-demented Chinese elderly male were recruited and underwent Cognitive Abilities Screening Instrument (CASI), Wechsler Digit Span Task, Geriatric Depression Scale-short form, and UCLA Loneliness Scale assessment. IL-1A rs1800587 is a C to T transition at position -889. Compared to the C/C carriers, the T allele carriers had significantly overall higher CASI score (p=0.017) after using age and total education years as co-variates. This was especially true in the four distinct domains of long-term memory (p<0.001), orientation (p=0.017), visual construction (p=0.003), and list-generating fluency (p=0.020). This polymorphism is not associated with Geriatric Depression Scale-short form or UCLA Loneliness Scale. Our data supports that the T allele of IL-1A rs1800587 genetic polymorphism is associated with better cognitive function in the elderly. Further research will be needed to better understand the molecular mechanism for IL-1A genetic effects on cognitive function in the elderly.

Effect of Bcl-2 rs956572 polymorphism on age-related gray matter volume changes.

The anti-apoptotic protein B-cell CLL/lymphoma 2 (Bcl-2) gene is a major regulator of neural plasticity and cellular resilience. Recently, the Bcl-2 rs956572 single nucleotide polymorphism was proposed to be a functional allelic variant that modulates cellular vulnerability to apoptosis. Our cross-sectional study investigated the genetic effect of this Bcl-2 polymorphism on age-related decreases in gray matter (GM) volume across the adult lifespan. Our sample comprised 330 healthy volunteers (191 male, 139 female) with a mean age of 56.2±22.0 years (range: 21-92). Magnetic resonance imaging and genotyping of the Bcl-2 rs956572 were performed for each participant. The differences in regional GM volumes between G homozygotes and A-allele carriers were tested using optimized voxel-based morphometry. The association between the Bcl-2 rs956572 polymorphism and age was a predictor of regional GM volumes in the right cerebellum, bilateral lingual gyrus, right middle temporal gyrus, and right parahippocampal gyrus. We found that the volume of these five regions decreased with increasing age (all P<.001). Moreover, the downward slope was steeper among the Bcl-2 rs956572 A-allele carriers than in the G-homozygous participants. Our data provide convergent evidence for the genetic effect of the Bcl-2 functional allelic variant in brain aging. The rs956572 G-allele, which is associated with significantly higher Bcl-2 protein expression and diminished cellular sensitivity to stress-induced apoptosis, conferred a protective effect against age-related changes in brain GM volume, particularly in the cerebellum.

Complexity of spontaneous BOLD activity in default mode network is correlated with cognitive function in normal male elderly: a multiscale entropy analysis.

The nonlinear properties of spontaneous fluctuations in blood oxygen level-dependent (BOLD) signals remain unexplored. We test the hypothesis that complexity of BOLD activity is reduced with aging and is correlated with cognitive performance in the elderly. A total of 99 normal older and 56 younger male subjects were included. Cognitive function was assessed using Cognitive Abilities Screening Instrument and Wechsler Digit Span Task. We employed a complexity measure, multiscale entropy (MSE) analysis, and investigated appropriate parameters for MSE calculation from relatively short BOLD signals. We then compared the complexity of BOLD signals between the younger and older groups, and examined the correlation between cognitive test scores and complexity of BOLD signals in various brain regions. Compared with the younger group, older subjects had the most significant reductions in MSE of BOLD signals in posterior cingulate gyrus and hippocampal cortex. For older subjects, MSE of BOLD signals from default mode network areas, including hippocampal cortex, cingulate cortex, superior and middle frontal gyrus, and middle temporal gyrus, were found to be positively correlated with major cognitive functions, such as attention, orientation, short-term memory, mental manipulation, and language. MSE from subcortical regions, such as amygdala and putamen, were found to be positively correlated with abstract thinking and list-generating fluency, respectively. Our findings confirmed the hypothesis that complexity of BOLD activity was correlated with aging and cognitive performance based on MSE analysis, and may provide insights on how dynamics of spontaneous brain activity relates to aging and cognitive function in specific brain regions.

Effect of Bcl-2 rs956572 SNP on regional gray matter volumes and cognitive function in elderly males without dementia.

The Bcl-2 gene is a major regulator of neural plasticity and cellular resilience. A single-nucleotide polymorphism (SNP) in the Bcl-2 gene, Bcl-2 rs956572, significantly modulates the expression of Bcl-2 protein and cellular vulnerability to apoptosis. This study investigated the association between the Bcl-2 rs956572 SNP and brain structural abnormalities in non-demented elders, and to test the relationship between neuropsychological performance and regional gray matter (GM) volumes. Our sample comprised 97 non-demented elderly men with a mean age of 80.6 ± 5.6 years (range, 65 to 92 years). Cognitive test results, magnetic resonance imaging, and genotyping of Bcl-2 rs956572 were examined for each subject. The differences in regional GM volumes between G homozygotes and A-allele carriers were tested using optimized voxel-based morphometry. Subjects with G homozygotes exhibited significantly worse performance in the language domain of the Cognitive Abilities Screening Instrument (CASI; p = 0.009). They also showed significantly smaller GM volumes in the right middle temporal gyrus (MTG) (BA 21), but larger GM volumes in the left precuneus (BA 31), right lingual gyrus (BA 18), and left superior occipital gyrus (BA 19) relative to A-allele carriers (p < 0.001). A trend toward a positive correlation between right MTG GM volumes and the language domain of CASI was also evident (r = 0.181; p = 0.081). The findings suggest that Bcl-2 rs956572 SNP may modulate cognitive function and regional GM volume in non-demented elderly men, and that this polymorphism may affect language performance through its effect on the right MTG.

Association of MTHFR C677T polymorphism with loneliness but not depression in cognitively normal elderly males.

Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism is involved in folate and homocysteine metabolism, and has been associated with geriatric disorders, including dementia and late-life depression. The present work aimed to investigate the effect of MTHFR C677T polymorphism on the presence of depression and loneliness in cognitively normal male subjects. A total of 323 cognitively normal male subjects were included in this study (mean age=80.6; SD=5.3). Depression was assessed by the Geriatric Depression Scale-Short Form (GDS-SF) and loneliness by UCLA loneliness scales. Analysis of variance (ANOVA) was used to test the between MTHFR genotype difference in depression and loneliness. Multiple regression was used to test the effect of MTHFR polymorphism on the loneliness, controlling for age, education, cognitive function, and depression. ANOVA showed a significant between-genotype difference in loneliness scores (P=0.015), and post hoc comparisons showed that subjects with C/C genotype had significantly higher loneliness ratings, compared to those with C/T or T/T genotype. Regression analysis indicated that the effect of MTHFR polymorphism on loneliness was independent of age, education, cognitive function, and depression. Our findings suggest that MTHFR C677T polymorphism may be linked more to loneliness than depression in the cognitively normal elderly males, and may be implicated in the pathophysiology of late-life depression in relation to MTHFR genes.

Association of lower hemoglobin levels with depression, though not with cognitive performance, in healthy elderly men.

Lower hemoglobin (Hb) levels are a common feature in the elderly. The present study recruited 180 healthy elderly men. Participants were assessed using the Geriatric Depression Scale, the Cognitive Abilities Screening Instrument Chinese version, and the Wechsler Digit Span Task test. The mean age of the participants was 85.8 years (SD = 10.5). Pearson's correlation tests demonstrated that Hb concentrations negatively correlated with Geriatric Depression Scale (r = -0.245, P = 0.001), but did not correlate with Cognitive Abilities Screening Instrument, Forward or Backward Digit Span tests. Lower Hb levels, therefore, were associated with depression in the elderly men.

Heterozygote advantage of the MTHFR C677T polymorphism on specific cognitive performance in elderly Chinese males without dementia.

AIMS: Aging is associated with cognitive deterioration, and genetic factors are implicated in individual cognitive differences in the aged. The C677T mutation in the 5,10-methylenetetrahydrofolate reductase gene (MTHFR) yields a common thermolabile variant (T) with reduced enzyme activity and consequent elevation of serum homocysteine concentrations. We designed the present study to investigate whether this functional polymorphism may affect global and specific cognitive functions in older Chinese males without dementia. METHODS: The subjects included 356 elderly males without major psychiatric disorders or dementia, who were assessed by the Cognitive Abilities Screening Instruments (CASI) and the Wechsler Digit Span Task tests. RESULTS: A significant association was found between the MTHFR C677T polymorphism and total CASI scores (p = 0.012), particularly in short-term memory (p = 0.002) and concentration/mental manipulation (p = 0.007). Post hoc tests indicated that the C/T heterozygotes achieved better cognitive function test results than C/C or T/T carriers. No association was found between the MTHFR genotype and the Wechsler Digit Span Task tests. CONCLUSION: These results suggest that a heterozygote advantage exists for the MTHFR C677T polymorphism in specific cognitive functions in elderly Chinese males without dementia.

Polymorphisms in LMNA and near a SERPINA13 gene are not associated with cognitive performance in Chinese elderly males without dementia.

Aging is associated with cognitive deterioration. A recent study showed two polymorphisms (rs505058 in LMNA and rs11622883 near a SERPINA13 gene), identified in a genome-wide association study of late-onset Alzheimer's disease, to be associated with cognitive function (Mini Mental State Examination) in a UK elderly population. This study replicated these findings in Chinese elderly males without dementia. A total of 358 elderly subjects were assessed by the Cognitive Abilities Screening Instruments (CASI) and the Wechsler Digit Span Task tests. Analysis of covariance was used to compare cognitive scores among genotypic groups, with age and total education years as covariates. The two polymorphisms were not associated with the global cognitive function or specific cognitive domains in the elderly without dementia. Our data argue against that these two polymorphisms may affect cognitive function in the elderly.

No association of angiotensin I converting enzyme I/D polymorphism with domain-specific cognitive function in aged men without dementia.

Previous research studies have related the insertion/deletion (I/D) polymorphism of the angiotensin I converting enzyme (ACE) gene to cognitive function in various neuropsychiatric or neurodegenerative disorders, but not yet investigated its genetic association with specific cognitive domains. Thus, the aim of this study was to assess the possible association of the ACE I/D polymorphism with domain-specific cognitive function in normal cognitive aging. Four hundred and sixty-nine-aged ethnic Chinese men without dementia were enrolled for genotyping and evaluated using several neuropsychological tests [Mini-Mental Status Examination (MMSE), Digit Span Forward and Backward, and Cognitive Ability Screening Instrument Chinese language version (CASI C-2.0)]. No direct association was found between ACE genotypes and the MMSE, Digit Span tests, or CASI total scores. Although subjects with I/I genotype had the lowest cognitive performance in the CASI visual construction domain (P = 0.031), this statistical difference disappeared after correction for multiple comparisons. This study suggests that the ACE I/D polymorphism does not have any genetic association with global or specific cognitive domain in aged men without dementia.

Lithium may be useful in the prevention of Alzheimer's disease in individuals at risk of presenile familial Alzheimer's disease.

Alzheimer's disease (AD) is the most common form of dementia among older people. Presenile familial AD (FAD) and sporadic Alzheimer's disease (SAD) have identical brain lesions, containing senile plaques with beta-amyloid (Abeta) peptide and neurofibrillary tangles formed by hyperphosphorylation of a microtubule-associated protein known as tau. However, FAD and SAD differ in onset and genetic transmission. Unlike SAD, presenile FAD is transmitted as a pure autosomal dominant trait. The authors suggest that lithium could be used for AD prevention, particularly in individuals at risk of presenile FAD, which has early onset. Evidence supporting this hypothesis suggests that lithium decreases Abeta peptide production and inhibits the activity of glycogen synthase kinase-3 which induces aggregation of tau protein into tangles, and tau hyperphosphorylation. Prevalence of AD is lower in patients with chronic lithium treatment, which also increases brain-derived neurotrophic factor activity, so might prevent onset in patients at risk for AD. Several considerations are suggested for prevention trials: the effect of lithium could be evaluated in young animal models that express presenile FAD mutant genes; the time, dose, duration and monitoring of lithium therapy are considered; early phenotypes could be monitored for treatment effect; and some other agents, like valproic acid, could also be candidates for prevention.