The Effect of Daily Low Dose Tadalafil on Cerebral Perfusion and Cognition in Patients with Erectile Dysfunction and Mild Cognitive Impairment

OBJECTIVE: The aims of this study were to investigate the effects of daily low-dose tadalafil on cognitive function and to examine whether there was a change in cerebral blood flow (CBF) in patients with erectile dysfunction (ED) and mild cognitive impairment. METHODS: Male patients aged 50 to 75 years with at least three months of ED (International Index of Erectile Function [IIEF]-5 score ≤ 21) and mild cognitive impairment (Montreal Cognitive Assessment [MoCA] score ≤ 22) were included in the study. The subjects were prescribed a low-dose PDE5 inhibitor (tadalafil 5 mg) to be taken once daily for eight weeks. Changes in MoCA score and single-photon emission computed tomography (SPECT) study between the two time-points were assessed by paired t tests. RESULTS: Overall, 30 male patients were assigned to the treatment group in this study and 25 patients completed the eight-week treatment course. Five patients were withdrawn due to adverse events such as myalgia and dizziness. Mean baseline IIEF and MoCA scores were 7.52 ± 4.84 and 18.92 ± 1.78. After the eight-week treatment, mean IIEF and MoCA scores were increased to 12.92 ± 7.27 (p < 0.05) and 21.8 ± 1.71 (p < 0.05), respectively. Patients showed increased relative regional CBF in the postcentral gyrus, precuneus, and brainstem after tadalafil administration versus at baseline (p < 0.001). CONCLUSION: The results of this prospective clinical study suggest that daily use of tadalafil 5 mg increases some regional CBF and improves cognitive function in patients with ED and mild cognitive impairment.

Animal Models of Demyelination and ¹H-Magnetic Resonance Spectroscopy

The proton magnetic resonance spectroscopy (¹H-MRS) is a tool used to detect concentrations of brain metabolites such as N-acetyl aspartate, choline, creatine, glutamate, and gamma-amino butyric acid (GABA). It has been widely used because it does not require additional devices other than the conventional magnetic resonance scanner and coils. Demyelination, or the neuronal damage due to loss of myelin sheath, is one of the common pathologic processes in many diseases including multiple sclerosis, leukodystrophy, encephalomyelitis, and other forms of autoimmune diseases. Rodent models mimicking human demyelinating diseases have been induced by using virus (e.g., Theiler's murine encephalomyelitis virus) or toxins (e.g., cuprizon or lysophosphatidyl choline). This review is an overview of the MRS findings on brain metabolites in demyelination with a specific focus on rodent models.

Associations between Brain Perfusion and Sleep Disturbance in Patients with Alzheimer's Disease

BACKGROUND AND PURPOSE: Although sleep disturbances are common and considered a major burden for patients with Alzheimer's disease (AD), the fundamental mechanisms underlying the development and maintenance of sleep disturbance in AD patients have yet to be elucidated. The aim of this study was to examine the correlation between regional cerebral blood flow (rCBF) and sleep disturbance in AD patients using technetium-99m hexamethylpropylene amine oxime single-photon emission computed tomography (SPECT). METHODS: A total of 140 AD patients were included in this cross-sectional study. Seventy patients were assigned to the AD with sleep loss (SL) group and the rest were assigned to the AD without SL group. SL was measured using the sleep subscale of the Neuropsychiatric Inventory. A whole-brain voxel-wise analysis of brain SPECT data was conducted to compare the rCBF between the two groups. RESULTS: The two groups did not differ in demographic characteristics, severity of dementia, general cognitive function, and neuropsychiatric symptoms, with the exception of sleep disturbances. The SPECT imaging analysis displayed decreased perfusion in the bilateral inferior frontal gyrus, bilateral temporal pole, and right precentral gyrus in the AD patients with SL group compared with the AD patients without SL group. It also revealed increased perfusion in the right precuneus, right occipital pole, and left middle occipital gyrus in the AD with SL group compared with the AD without SL group. CONCLUSIONS: The AD patients who experienced sleep disturbance had notably decreased perfusion in the frontal and temporal lobes and increased rCBF in the parietal and occipital regions. The findings of this study suggest that functional alterations in these brain areas may be the underlying neural correlates of sleep disturbance in AD patients.

Changes in Regional Cerebral Perfusion after Nicergoline Treatment in Early Alzheimer's Disease: A Pilot Study

BACKGROUND AND PURPOSE: Nicergoline is an ergoline derivative that is used to treat cognitive deficits in cerebrovascular disease and various forms of dementia. Although therapeutic effects of nicergoline have been established, little is known about its effects on cerebral perfusion in Alzheimer's disease (AD). The aim of this study was to examine the role of nicergoline in regional cerebral blood flow (rCBF) of AD patients using technetium-99m hexa-methyl-propylene-amine-oxime single photon emission computed tomography (SPECT). METHODS: Sixteen patients with early AD underwent a comprehensive clinical assessment including cognitive testing and SPECT scans before and after nicergoline treatment. Nicergoline (30 mg twice daily) was administered for an average duration of 1.5 years. Clinical and cognitive functioning was assessed using the Mini-Mental State Examination, Clinical Dementia Rating (CDR), CDR-Sum of Boxes, Global Deterioration Scale, Barthel Activities of Daily Living Index, Instrumental Activities of Daily Living, and Geriatric Depression Scale. RESULTS: Nicergoline treatment induced changes in the severity of dementia, cognitive function, activities of daily living, and depressive symptoms, which were not statistically significant. During the follow-up, the patients showed significant increases in their relative rCBF in the superior frontal gyrus, precentral gyrus, and postcentral gyrus. CONCLUSIONS: Nicergoline treatment improves perfusion of the frontal and parietal regions in early AD patients. It is possible that the increased perfusion in the superior frontal gyrus may be related to the mechanisms that delay or prevent progressive deterioration of cognitive functions in AD.

Cerebral Perfusion Changes after Acetyl-L-Carnitine Treatment in Early Alzheimer's Disease Using Single Photon Emission Computed Tomography

BACKGROUND AND PURPOSE: Although acetyl-L-carnitine (ALC) treatment may have beneficial effects on Alzheimer's disease (AD), its underlying neural correlates remain unclear. The purpose of this study was to investigate cerebral perfusion changes after ALC treatment in AD patients using technetium-99m hexamethylpropylene amine oxime single photon emission computed tomography (SPECT). METHODS: A total of 18 patients with early AD were prospectively recruited and treated with ALC at 1.5 g/day for 1.4±0.3 years. At baseline and follow-up, brain SPECT, Mini-Mental State Examination (MMSE), Clinical Dementia Rating (CDR), Global Deterioration Scale (GDS), and Neuropsychiatric Inventory (NPI) were used to assess participants. After ALC administration, changes in brain perfusion, severity of dementia, cognitive performance, and neuropsychiatric disturbances were examined. RESULTS: After ALC administration, changes in scores of MMSE, CDR, GDS, and NPI were not statistically significant (p>0.05). Voxel-wise whole-brain image analysis revealed that perfusion was significantly (p<0.001) increased in the right precuneus whereas perfusion was reduced in the left inferior temporal gyrus (p<0.001), the right middle frontal gyrus (p<0.001), and the right insular cortex (p=0.001) at follow-up. CONCLUSIONS: Although previous studies have suggested that AD patients generally demonstrate progressive deterioration in brain perfusion and clinical symptoms, this study reveals that the perfusion of the precuneus is increased in AD patients after ALC administration and their cognitive and neuropsychiatric symptoms are not aggravated. Further studies are warranted to determine the potential association between perfusion increase in the precuneus and clinical symptoms after ALC treatment in AD patients.

Reliability and Validity of the Korean Version of the Post-Traumatic Stress Disorder Checklist in Public Firefighters and Rescue Workers

OBJECTIVES: Firefighters and rescue workers are likely to be exposed to a variety of traumatic events; as such, they are vulnerable to the risk of post-traumatic stress disorder (PTSD). The psychometric properties of the Korean version of the PTSD Checklist (PCL), a widely used self-report screening tool for PTSD, were assessed in South Korean firefighters and rescue workers. METHODS: Data were collected via self-report questionnaires and semi-structured clinical interviews administered to 221 firefighters. Internal consistency, item-total correlation, one-week test-retest reliability, convergent validity, and divergent validity were examined. Content validity of the PCL was evaluated using factor analysis and receiver operating characteristic (ROC) analyses were used to estimate the optimal cutoff point and area under the curve. RESULTS: The PCL demonstrated excellent internal consistency (alpha = 0.97), item-total correlation (r = 0.72-0.88), test-retest reliability (r = 0.95), and convergent and divergent validity. The total score of PCL was positively correlated with the number of traumatic events experienced (p < 0.001). Factor analysis revealed two theoretically congruent factors: re-experience/avoidance and numbing/hyperarousal. The optimal cutoff was 45 and the area under the ROC curve was 0.97. CONCLUSIONS: The Korean version of the PCL may be a useful PTSD screening instrument for firefighters and rescue workers, further maximizing opportunities for accurate PTSD diagnosis and treatment.

Neurocriminology : A Review on Aggression and Criminal Behaviors Using Brain Imaging

Criminology has been understood within a sociological framework until the emergence of neurocriminology, which describes, understands and predicts criminal behaviors from a neurobiological point of view. Not only using biological factors including genes and hormones to understand criminal behaviors, but also using neuroimaging techniques, the field of neurocriminology aims to delve into both structural and functional differences in the brain of individuals with aggression, antisocial personalities, and even the criminals. Various studies have been conducted based on this idea, however, there still are limitations for the knowledge from these studies to be used in the court. In this review article, we provide an overview of the various research in neurocriminology, and provide insight into the future direction and implication of the field.

Aggression and Neurotransmitters

Aggression and aggressive behaviors, often explained as harmful social interaction with the intention of hurting or inflicting damage upon another, have been considered as an adaptive mechanism from the evolutionary psychological point of view. However, various studies on aggression and aggressive behaviors have been done with psychopathological approach as the extreme aggressive behaviors may harm themselves and others at the same time. Recently, researchers have attempted to explain aggression in terms of neurobiological substrates rather than based on traditional psychopathological and/or behavioral concept. In this regard, there have been findings of differences in neurotransmitters and their receptors, and genetic polymorphisms. In this review article, we provide a brief overview of the literature about seven most frequently reported neurotransmitters including neurohormones (serotonin, norepinephrine, dopamine, gamma-aminobutyric acid, nitric oxide, oxytocin and vasopressin) and an associated enzyme (monoamine oxidase A), which are known to be related with aggression and aggressive behaviors.

Long-Term Efficacy of Memantine in Parkinson' Disease Dementia: An 18-Month Prospective Perfusion Single Photon Emission Computed Tomography Preliminary Study

BACKGROUND AND PURPOSE: Although the treatment efficacy of memantine in Parkinson's disease dementia (PDD) has been reported after several weeks of administration, the long-term effects on brain perfusion and clinical symptoms remain unclear. The current study aimed to follow-up PDD patients after 18 months of memantine treatment using (99m)Tc hexamethylpropylene amine oxime single photon emission computed tomography (SPECT). METHODS: A total of 15 patients with PDD and 11 healthy participants were recruited into this study and they were assessed with brain SPECT, Mini-Mental State Examination (MMSE), Clinical Dementia Rating (CDR), Global Deterioration Scale (GDS), and Neuropsychiatric Inventory (NPI). Differences in regional cerebral blood flow (rCBF) between the two groups were evaluated at baseline. After 18 months of memantine administration, changes in brain perfusion, severity of dementia, cognition, and neuropsychiatric disturbances were examined in the patients with PDD. RESULTS: The PDD group showed hypoperfusion in most of the cortical, subcortical, and cerebellar areas compared to healthy controls at baseline. At the follow-up, changes in rCBF, CDR (p=0.32), sum of box of CDR (p=0.49), MMSE (p=0.61), GDS (p=0.79), and NPI (p=0.23) were not significant in the PDD patients. CONCLUSIONS: Our findings implicate that memantine may delay the progression of brain perfusion deficits and clinical symptoms of PDD in the long term.

Longitudinal Cerebral Perfusion Changes in Parkinson's Disease with Subjective Cognitive Impairment

BACKGROUND AND PURPOSE: Although subjective cognitive impairment (SCI) is often accompanied by Parkinson's disease (PD) and may predict the development of mild cognitive impairment or dementia, longitudinal brain perfusion changes in PD patients with SCI remain to be elucidated. The current prospective study examined cerebral perfusion changes in PD patients with SCI using technetium-99m hexamethylpropylene amine oxime single photon emission computed tomography (SPECT). METHODS: Among 53 PD patients at baseline, 30 patients were classified into the PD with SCI group and 23 patients were assigned to the PD without SCI group. The mean follow-up interval was 2.3±0.9 years. The Mini-Mental State Examination, Clinical Dementia Rating, and Global Deterioration Scale were used to assess impairments in cognitive function. Brain SPECT images were acquired at baseline and follow-up. RESULTS: Significant differences between the two groups were not found for demographic variables, PD severity, or cognitive function at either baseline or follow-up. At baseline, the PD with SCI group showed decreased perfusion in the left angular gyrus compared to the PD without SCI group. Longitudinal analysis revealed widespread perfusion reductions primarily in the bilateral temporo-parieto-occipital areas and cerebellum in the PD with SCI group. Relative to the PD without SCI group, an excessive decrease of perfusion was found in the left middle frontal gyrus of the PD with SCI patients. CONCLUSIONS: Our findings suggest that perfusion deficits in the middle frontal area may play an important role in the pathophysiology of SCI in PD.

Effects of Korean Red Ginseng on White Matter Microstructure and Cognitive Functions: A Focus on Intrusion Errors

OBJECTIVES: Although ginseng has been reported to protect neuronal cells and improve various cognitive functions, relationship between ginseng supplementation and response inhibition, one of the important cognitive domains has not been explored. In addition, effects of ginseng on in vivo human brain have not been investigated using the diffusion tensor imaging (DTI). The purpose of the current study is to investigate changes in intrusion errors and white matter microstructure after Korean Red Ginseng supplementation using standardized neuropsychological tests and DTI. METHODS: Fifty-one healthy participants were randomly allocated to the Korean Red Ginseng (n = 26) or placebo (n = 25) groups for 8 weeks. The California Verbal Learning Test was used to assess the number of intrusion errors. Intelligence quotient (IQ) was measured with the Korean Wechsler Adult Intelligence Scale. Depressive and anxiety symptoms were evaluated using Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, and Hopkins Symptom Checklist-25. The fractional anisotropy (FA) was measured from the brain DTI data. RESULTS: After the 8-week intervention, Korean Red Ginseng supplementation significantly reduced intrusion errors after adjusting age, sex, IQ, and baseline score of the intrusion errors (p for interaction = 0.005). Change in FA values in the left anterior corona radiata was greater in the Korean Red Ginseng group compared to the placebo group (t = 4.29, p = 0.04). CONCLUSIONS: Korean Red Ginseng supplementation may be efficacious for improving response inhibition and white matter microstructure integrity in the prefrontal cortex.

Advances in Functional Connectomics in Neuroscience : A Focus on Post-Traumatic Stress Disorder

Recent breakthroughs in functional neuroimaging techniques have launched the quest of mapping the connections of the human brain, otherwise known as the human connectome. Imaging connectomics is an umbrella term that refers to the neuroimaging techniques used to generate these maps, which recently has enabled comprehensive brain mapping of network connectivity combined with graph theoretic methods. In this review, we present an overview of the key concepts in functional connectomics. Furthermore, we discuss articles that applied task-based and/or resting-state functional magnetic resonance imaging to examine network deficits in post-traumatic stress disorder (PTSD). These studies have provided important insights regarding the etiology of PTSD, as well as the overall organization of the brain network. Advances in functional connectomics are expected to provide insight into the pathophysiology and the development of biomarkers for diagnosis and treatment of PTSD.

Reliability and Validity of the Fatigue Severity Scale among University Student in South Korea

OBJECTIVES: There are only a limited number of studies on instruments assessing fatigue in university students, although fatigue exerts negative influences on their health and academic performances and fatigue-related complaints are more frequently reported in young adults than middle-aged adults. The aim of this study was to validate the 9-item Fatigue Severity Scale (FSS) among university students including both undergraduate and graduate students in South Korea. METHODS: A total of 176 university students completed a battery of self-report questionnaires, including the FSS, the Brief Fatigue Inventory (BFI), the Beck Depression Inventory-II (BDI-II), the Beck Anxiety Inventory (BAI), the Medical Outcomes Study Short Form 36 version 2 (MOS-SF36v2), and the Inclusion of Community in the Self Scale (ICS). The data were collected from February of 2012 to June of 2012. The reliability, convergent validity, divergent validity, and exploratory factor analyses were conducted to assess psychometric properties of the FSS. RESULTS: The mean FSS score was 3.20 (standard deviation = 1.43). The FSS demonstrated an excellent internal consistency (Cronbach's alpha = 0.93) and item-total correlations ranged from 0.56 to 0.90. Correlations of the FSS with the BFI (r = 0.71, p < 0.01), BDI-II (r = 0.54, p < 0.01), BAI (r = 0.46, p < 0.01), MOS-SF36v2 physical component summary (r = -0.28, p < 0.01), MOS-SF36v2 mental component summary (r = -0.55, p < 0.01), and ICS (Spearman's rho = -0.07, p = 0.33) showed acceptable convergent and divergent validity. Exploratory factor analysis defined one underlying factor (eigenvalue = 5.67) that explained 93.50% of the total variance. CONCLUSIONS: To the best of our knowledge, this is the first study to investigate reliability and validity of the FSS in university students. The FSS exhibits good psychometric properties for evaluation of fatigue among university students in South Korea. Since the FSS is easy to administer, score, and interpret, it could be a useful tool in research and practice for assessing fatigue among university students.

Reliability and Validity of the Korean Version of the Lifespan Sibling Relationship Scale

The sibling relationship and its potential impact on neurodevelopment and mental health are important areas of neuroscientific research. Validation of the tools assessing the quality of the sibling relationship would be the first essential step for conducting neurobiological and psychosocial studies related to the sibling relationship. However, to the best of our knowledge, no sibling relationship assessment tools have been empirically validated in Korean. We aimed to evaluate the psychometric properties of the Korean version of the Lifespan Sibling Relationship Scale (LSRS), which is one of the most commonly used self-report questionnaires to assess the quality of the sibling relationship. A total of 109 adults completed a series of self-report questionnaires including the LSRS, the mental health subscale of the Medical Outcomes Study-Short Form 36 version 2 (SF36v2), the Satisfaction with Life Scale (SLS), and the Marlowe-Crowne Social Desirability Scale (MC-SDS). The internal consistency, subscale intercorrelations, one-week test-retest reliability, convergent validity, divergent validity, and the construct validity were assessed. All six subscale scores and the total score of the LSRS demonstrated good internal consistency (Cronbach's alpha=0.85-0.94) and good test-retest reliability (intraclass correlation coefficient=0.77-0.92). Correlations of the LSRS with the SF36v2 mental health score (r=0.32, p=0.01) and with the SLS (r=0.27, p=0.04) supported the good convergent validity. The divergent validity was shown by the non-significant correlation of the LSRS with the MC-SDS (r=0.15, p=0.26). Two factors were extracted through factor analysis, which explained 78.63% of the total variance. The three Adult subscales loaded on the first factor and the three Child subscales loaded on the second factor. Results suggest that the Korean version of the LSRS is a reliable and valid tool for examining the sibling relationship.