The Ankle-Brachial Index Is Associated with Cerebral ß-Amyloid Deposition in Cognitively Normal Older Adults.

BACKGROUND: Although ankle-brachial index (ABI), an indicator of atherosclerosis or arterial stiffness, has been associated with dementia and Alzheimer's disease (AD), no information is yet available for its contribution to AD pathologies. We investigated the relationship between the ABI and in vivo ß-amyloid (Aß) deposition and AD-specific neurodegeneration in cognitively normal (CN) elderly individuals. METHODS: A total of 256 CN elderly subjects who participated in the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's Disease (KBASE), an ongoing prospective cohort study, were included. All subjects underwent comprehensive clinical and neuropsychological assessments, ABI measurement, apolipoprotein E (APOE) genotyping, [11C]Pittsburgh Compound B (PiB)-positron emission tomography (PET), [18F]-fludeoxyglucose PET, and magnetic resonance imaging. RESULTS: A significant positive association was found between the ABI and global cerebral Aß retention measured by PiB-PET, even after controlling for age, sex, and APOE ε4. When three stratified ABI subgroups (ABI < 1.00, 1.00-1.29, and ≥ 1.30) were compared, the highest ABI subgroup (ie, ABI ≥ 1.30) showed significantly higher Aß deposition than that of the other subgroups. This relationship between Aß deposition and the ABI was significant only in APOE ε4 carriers, but not in noncarriers. No significant association was observed between the ABI and neurodegeneration in the AD-signature regions. CONCLUSION: Our findings suggest that a high ABI, possibly related to arterial stiffness, is associated with elevated brain Aß burden in cognitively healthy elderly individuals, particularly in APOE ε4 carriers.

Balance Deficit and Brain Connectivity in Children with Attention-Deficit/Hyperactivity Disorder.

OBJECTIVE: We aimed to assess disturbances in postural and gait balance and functional connectivity within the brain regions controlling balance in children with attention-deficit/hyperactivity disorder (ADHD). METHODS: Thirteen children with ADHD and 13 age- and sex-matched controls were recruited. Gait balance was assessed by the difference in the center of pressure (COP) between the left and right foot, as well as the difference in plantar pressure between the left and right foot during gait. Neuroimaging data were acquired using a 3.0 Tesla MRI scanner. Functional connectivity between the vermis of the cerebellum and all other brain regionswas assessed. RESULTS: The difference in plantar pressure between the left foot and right foot in the ADHD group was greater than that observed in the control group. The average COP jerk score of the right foot in the ADHD group was higher than that observed in the control group. A higher functional connectivity between the cerebellum and the right middle frontal gyrus (premotor cortex) and medial frontal gyrus (cingulate gyrus) was observed in the control group relative to the ADHD group. In the ADHD group, the difference in plantar pressure between the left and right foot was also negatively correlated with the beta-value within the middle frontal gyrus. CONCLUSION: Children with ADHD had disturbance of balance as assessed by plantar pressure. Decreased brain connectivity from the cerebellum to the premotor cortex and anterior cingulate was associated with disturbances of posture and balance in children with ADHD.

Incidence and Course of Depression in Patients with Alzheimer's Disease.

OBJECTIVE: Depressive symptoms are common in Alzheimer's disease (AD) and they might influence the course and prognosis of AD. Depression could appear anytime in the course of the disease, and could either last considerably long or disappear easily. This study is intended to investigate the occurrence of depression in the course of AD and the risk factors of incidence. METHODS: This study targeted 1,272 AD patients without depressive symptoms at the start of this study in Korea. A total of 775 subjects completed the study, and the occurrence of depression was assessed after 12 months. Demographic information of subjects was collected and cognitive functions, overall functions, and depression severity were assessed at the start of this study and after 12 months. RESULTS: Among the 775 subjects, 103 subjects (13.29%) developed depression 12 months later. The MMSE-KC scores showed significant changes in both groups that developed depression and did not. In the univariate analysis, significant differences in the incidence of depression were found in terms of gender, the administration of the antidepressant at the baseline, the SGDS-K score, and the GDS score. The multiple logistic regression analysis showed that the increase in the incidence of depression was associated with a female, in the increase in SGDS-K score and the GDS score. CONCLUSION: The incidence of depression in the subjects who completed the 12-month follow-up observation was 13.29%. Moreover, in the multivariate analysis, a female gender and the severity of dementia, including the overall functions, seemed associated with the occurrence of depression.

Comparison of QEEG Findings between Adolescents with Attention Deficit Hyperactivity Disorder (ADHD) without Comorbidity and ADHD Comorbid with Internet Gaming Disorder.

Internet gaming disorder (IGD) is often comorbid with attention deficit hyperactivity disorder (ADHD). In this study, we compared the neurobiological differences between ADHD comorbid with IGD (ADHD+IGD group) and ADHD without comorbidity (ADHD-only group) by analyzing quantitative electroencephalogram (QEEG) findings. We recruited 16 male ADHD+IGD, 15 male ADHD-only adolescent patients, and 15 male healthy controls (HC group). Participants were assessed using Young's Internet Addiction Scale and ADHD Rating Scale. Relative power and inter- and intra-hemispheric coherences of brain waves were measured using a digital electroencephalography (EEG) system. Compared to the ADHD-only group, the ADHD+IGD group showed lower relative delta power and greater relative beta power in temporal regions. The relative theta power in frontal regions were higher in ADHD-only group compared to HC group. Inter-hemispheric coherence values for the theta band between F3-F4 and C3-C4 electrodes were higher in ADHD-only group compared to HC group. Intra-hemispheric coherence values for the delta, theta, alpha, and beta bands between P4-O2 electrodes and intra-hemispheric coherence values for the theta band between Fz-Cz and T4-T6 electrodes were higher in ADHD+IGD group compared to ADHD-only group. Adolescents who show greater vulnerability to ADHD seem to continuously play Internet games to unconsciously enhance attentional ability. In turn, relative beta power in attention deficit in ADHD+IGD group may become similar to that in HC group. Repetitive activation of brain reward and working memory systems during continuous gaming may result in an increase in neuronal connectivity within the parieto-occipital and temporal regions for the ADHD+IGD group.

The comparison of temperament and character between patients with internet gaming disorder and those with alcohol dependence.

BACKGROUND: The differences in prevalence, natural history, and disease progression between Internet gaming disorder (IGD) and substance use disorder contribute to the controversy over IGD as a diagnosis under substance-related and addictive disorders. AIMS: The purpose of the current study was to assess the temperament and character of subjects with IGD in comparison with those with alcohol dependence (AD). METHODS: Temperament and character were assessed using Cloningernt temperament and character inventory (TCI). The severity of IGD or AD, depressed mood, anxiety, attention and impulsiveness were assessed using each of the six scales. RESULTS: Among patients with AD, after controlling for other variables, the severity of AD was positively correlated with harm avoidance (HA) score and depressed mood. Among patients with IGD, after controlling for other variables, the severity of IGD was positively correlated with novelty seeking (NS) score, impulsiveness and attention. CONCLUSIONS: There were significant differences in temperament and character between the IGD and AD groups as measured using the TCI. These results suggest that IGD and AD need to be categorized separately in a diagnostic classification system and benefit from different treatment approaches.

Opioid Analgesics and Depressive Symptoms in Burn Patients: What Is the Real Relationship?

OBJECTIVE: Major burn injuries are strongly associated with both psychological trauma and severe pain, and opioids are the mainstay analgesics for the treatment of severe burn pain. The objectives of this study are to find the complex relationship between opioid dose, depression, and post-traumatic stress disorder (PTSD) symptoms during the acute management of pain in burn patients. METHODS: The symptoms of depression and PTSD were assessed in 43 burn patients immediately following wound stabilization and 2 weeks after the initial evaluation. RESULTS: Total opioid doses and Hamilton Depression Scale (HAMD) scores obtained during the second evaluation were positively but weakly correlated after controlling for age and total burn surface area (R=0.33, p=0.03). Moreover, pain management with opioids was significantly more common in burn patients with low Clinician Administered PTSD Scale scores (evaluation 1) and high HAMD scores (evaluation 2) (F=6.66, p=0.001). CONCLUSION: High opioid dose following acute burn trauma might have correlation with depressive symptoms. Monitoring of depressive symptoms may be important following acute burn trauma and consequent opioids pain management, particularly when PTSD symptoms appear minimal during the early stabilization of patients.

Desynchronization of Theta-Phase Gamma-Amplitude Coupling during a Mental Arithmetic Task in Children with Attention Deficit/Hyperactivity Disorder.

INTRODUCTION: Theta-phase gamma-amplitude coupling (TGC) measurement has recently received attention as a feasible method of assessing brain functions such as neuronal interactions. The purpose of this electroencephalographic (EEG) study is to understand the mechanisms underlying the deficits in attentional control in children with attention deficit/hyperactivity disorder (ADHD) by comparing the power spectra and TGC at rest and during a mental arithmetic task. METHODS: Nineteen-channel EEGs were recorded from 97 volunteers (including 53 subjects with ADHD) from a camp for hyperactive children under two conditions (rest and task performance). The EEG power spectra and the TGC data were analyzed. Correlation analyses between the Intermediate Visual and Auditory (IVA) continuous performance test (CPT) scores and EEG parameters were performed. RESULTS: No significant difference in the power spectra was detected between the groups at rest and during task performance. However, TGC was reduced during the arithmetic task in the ADHD group compared with the normal group (F = 16.70, p < 0.001). The TGC values positively correlated with the IVA CPT scores but negatively correlated with theta power. CONCLUSIONS: Our findings suggest that desynchronization of TGC occurred during the arithmetic task in ADHD children. TGC in ADHD children is expected to serve as a promising neurophysiological marker of network deactivation during attention-demanding tasks.

Virtual Reality Therapy for the Treatment of Alcohol Dependence: A Preliminary Investigation With Positron Emission Tomography/Computerized Tomography.

OBJECTIVE: Virtual reality therapy (VRT) uses multimodal stimulation that includes visual, auditory, olfactory, and gustatory stimuli. The aim of this study was to assess the effectiveness of VRT in treating subjects with alcohol dependence (AD) by evaluating changes in brain metabolism. METHOD: The VRT protocol consisted of three steps: relaxation, presentation of a high-risk situation, and presentation of an aversive situation. Twelve alcohol-dependent subjects underwent 10 sessions of VRT. The alcohol-dependent subjects were assessed with 18F-fluorodeoxyglucose positron emission tomography images before and after VRT, whereas the control group underwent imaging according to the same protocol only at baseline. RESULTS: Compared with the healthy control group, AD subjects showed higher metabolism in the right lentiform nucleus and right temporal lobe (BA20) at baseline (P(FDR < .05) = .026). In addition, the metabolism in the left anterior cingulate was lower in subjects with AD (P(uncorr) = .001). After VRT, alcohol-dependent subjects showed decreased brain metabolism in the right lentiform nucleus (P(FDR < .05) = .026) and right temporal lobe (BA38, P(FDR < .05) = .032) relative to that at baseline. CONCLUSIONS: Our results suggest a neurobiological imbalance, notably, a high sensitivity to stimuli, in the limbic system in subjects with AD. Furthermore, we determined that metabolism decreased in the basal ganglia after VRT, which may explain the limbic-regulated responses of reward and regulation. Therefore, we tentatively recommend VRT to treat AD through its regulating effect on limbic circuits.

Correlation between gray matter volume in the temporal lobe and depressive symptoms in patients with Alzheimer's disease.

Recent studies have suggested that depression might be an aggravating factor in Alzheimer's disease (AD). The aim of the study was to compare depressive symptoms and gray matter volume between AD patients with comorbid depression and patients with dementia only. Forty-nine patients with AD, 57 with mild cognitive impairment (MCI), and 50 healthy control subjects were assessed using the Consortium to Establish a Registry for Alzheimer's disease (CERAD) and the Geriatric Depression Scale (GDS). All magnetic resonance imaging (MRI)s were analyzed using voxel-based morphometry (VBM). Seventeen AD patients with depression versus 32 patients with dementia only showed decreased immediate recall for a word list (8.7±1.1 vs. 10.1±1.5, z=3.6, p<0.01) and constructional praxis scores (3.7±0.9 vs. 5.3±2.1, z=2.5, p=0.01). Compared to 32 patients with dementia, seventeen AD patients with depression showed decreased gray matter volume in the left inferior temporal gyrus (-56, -19, -31; KE=578, t=3.80, Puncorr<0.001). The MCI group showed decreased gray matter volume in the right hippocampal gyrus compared to healthy control group. Our results suggest that depressive symptoms may be associated with the volume changes of frontal and temporal lobe in patients with AD.

Effects of antipsychotic drugs on the expression of synaptic proteins and dendritic outgrowth in hippocampal neuronal cultures.

Recent evidence has suggested that atypical antipsychotic drugs regulate synaptic plasticity. We investigated whether some atypical antipsychotic drugs (olanzapine, aripiprazole, quetiapine, and ziprasidone) altered the expression of synapse-associated proteins in rat hippocampal neuronal cultures under toxic conditions induced by B27 deprivation. A typical antipsychotic, haloperidol, was used for comparison. We measured changes in the expression of various synaptic proteins including postsynaptic density protein-95 (PSD-95), brain-derived neurotrophic factor (BDNF), and synaptophysin (SYP). Then we examined whether these drugs affected the dendritic morphology of hippocampal neurons. We found that olanzapine, aripiprazole, and quetiapine, but not haloperidol, significantly hindered the B27 deprivation-induced decrease in the levels of these synaptic proteins. Ziprasidone did not affect PSD-95 or BDNF levels, but significantly increased the levels of SYP under B27 deprivation conditions. Moreover, olanzapine and aripiprazole individually significantly increased the levels of PSD-95 and BDNF, respectively, even under normal conditions, whereas haloperidol decreased the levels of PSD-95. These drugs increased the total outgrowth of hippocampal dendrites via PI3K signaling, whereas haloperidol had no effect in this regard. Together, these results suggest that the up-regulation of synaptic proteins and dendritic outgrowth may represent key effects of some atypical antipsychotic drugs but that haloperidol may be associated with distinct actions.

A voxel-based morphometric study of cortical gray matter volume changes in Alzheimer's disease with white matter hyperintensities.

White matter hyperintensity (WMH) is commonly detected in patients with Alzheimer's disease (AD), but its role in cortical impairment is unclear. This study investigated the effects of WMH on gray matter (GM) volume in patients with AD. We consecutively enrolled 84 patients with AD and 35 normal controls, who underwent brain MRI and were then classified according to WMH grade, based on a combination of deep white matter hyperintensity (DWMH) and periventricular white matter hyperintensity (PVWMH). The volume changes in GM were observed using voxel-based morphometry. It was found that global GM volume decreased with increasing WMH. Regional atrophies were in the dorsolateral frontal lobes, orbitofrontal gyri and insula (false discovery rate [FDR], p<0.01). After controlling for PVWMH, DWMH affected cortical atrophy in the frontal lobe, insula and precuneus (FDR, p<0.05), but PVWMH did not. Thus, WMH in AD is associated with GM volume reduction, especially in the frontal lobe, and DWMH is independently related to cortical atrophy.

Performance enhancement with low stress and anxiety modulated by cognitive flexibility.

OBJECTIVE: The purpose of this study was to compare cognitive flexibility abilities, stress, and anxiety between starters and non-starter athletes. METHODS: A total of 30 male professional-soccer and 40 professional-baseball athletes were recruited. Wisconsin Card Sorting Test (WCST) and Trail Making Test A & B (TMT A & B) were administered to assess cognitive flexibility during competition. The Korean version of the STAI form Y (STAI-KY) and Visual analogue scale for anxiety and stress were used to assess the anxiety and stress. RESULTS: The starter group had better cognitive function (fewer perseverative errors and rapid TMTB times) (Z=3.32, p<0.01; Z=2.20, p=0.03, respectively) and lower stress and anxiety (F=4.34, p=0.01; F=6.61, p<0.01, respectively) during competition than the non-starter group. CONCLUSION: The better cognitive performances were negatively correlated with stress and anxiety. Current results suggested that cognitive flexibility would enhance human performance by modulation of the anxiety and stress during competition.

Voxel-based morphometric study of brain volume changes in patients with Alzheimer's disease assessed according to the Clinical Dementia Rating score.

We evaluated the volume reduction of gray matter (GM) and white matter (WM) in patients with an Alzheimer's disease (AD) assessment based on the Clinical Dementia Rating (CDR) score. Patients with AD (n=61), with no subcortical WM ischemia, and healthy control patients (n=33) underwent T1-weighted spoiled gradient echo sequences, which were analyzed using voxel-based morphometry. Global GM volume reduction was observed in patients with a CDR score of 1 or a CDR score of 2, and WM volume reduction was observed in patients with a CDR score of 2. Regional GM volume reduction was found in the right inferior frontal gyrus, bilateral dorso-lateral and medial temporal lobes; WM volume reduction was found in the bilateral temporal subcortex (family-wise error, p<0.01). A CDR score of 0.5 was associated with volume reduction in the left olfactory gyrus. The peak z-score and spatial extent of volume reduction increased with increasing CDR score and were higher on the left side. GM volume reduction increased with increasing CDR scores and suggests a possible pathomechanism of AD.

Cholinesterase inhibitors for Alzheimer disease: do they provide more than symptomatic benefits?

OBJECTIVE: This study aims to examine survival of patients with Alzheimer disease (AD) receiving clinical efficacy of cholinesterase inhibitors (ChEIs) and to compare their survival with those of patients with AD who never received ChEIs and cognitively intact old psychiatric outpatients. DESIGN, SETTING, AND PARTICIPANTS: The retrospective cohort study used national mortality data provided by the Korean National Statistics Office and electronic database of 15 general hospitals on older patients who began outpatient treatment with psychiatric medications including ChEIs (N = 3,813). The authors controlled for confounding by using multivariate models and propensity scoring methods. MEASUREMENTS: Mortality rate of patients with AD receiving ChEIs was compared with those of patients with AD who never received ChEIs and cognitively intact old psychiatric outpatients. RESULTS: Observed additional survival of patients with AD receiving ChEIs (mortality rate: 13.1%), when compared with patients with AD who never received ChEIs (15.4%) was not statistically significant (p = 0.74; hazard ratio [HR]: 1.03, 95% confidence interval [CI]: 0.67-1.59). Patients with AD receiving ChEIs showed higher mortality rate (13.1%) compared with that of cognitively intact old psychiatric outpatients (8.6%) (p <0.001; HR: 1.60, 95% CI: 0.96-2.68). CONCLUSION: This study does not support that ChEIs increase survival of patients with AD, compared with patients with AD who have never treated with ChEIs. Therefore, all ChEIs should be considered for symptomatic use only and not to be capable of modifying mortality of patients with AD.

A Case of Very-late-onset Schizophrenia-like Psychosis.

This paper presents the case of a 67-year-old woman who visited the Psychiatry Department complaining of persecutory ideas and auditory hallucinations after a buccal cancer operation. On neuropsychological testing, she demonstrated paranoid psychosis and bizarre thoughts. Hospital admission was recommended for supportive care and treatment with antipsychotics. She was initially treated with olanzapine, but this medication had little effect and was replaced with amisulpride, which reduced the residual symptoms. The aim of this report was to discuss the diagnostic process and treatment of very late-onset schizophrenia-like psychosis.

A preliminary study: novelty seeking, frontal executive function, and dopamine receptor (D2) TaqI A gene polymorphism in patients with methamphetamine dependence.

INTRODUCTION: Dopamine receptor polymorphisms have been associated with specific patterns of novelty seeking (NS) temperamental nature and frontal executive function. In addition, carriers of dopamine receptor type 2 (DRD2)-TaqI A1 have been hypothesized to be potentially vulnerable to addictive behaviors. In the present study, the association between dopamine D2 polymorphisms, NS, and frontal executive function was studied. METHODS: Thirty-seven methamphetamine (MA)-dependent subjects and 40 healthy comparison subjects participated in the current study. The severity of addiction, NS temperament, and frontal executive functions were measured using the Addiction Severity Index, the NS subscale in the Temperament and Character Inventory, and the Wisconsin Card Sorting Test, respectively. All subjects were genotyped with regard to DRD2-TaqI polymorphisms. RESULTS: The prevalence of DRD2-TaqI A1 allele polymorphisms was greater in the MA-abuser group than in the comparison group. Patients with MA dependence also had higher NS characteristics and high scores in total trials, errors, and perseverative errors of the Wisconsin Card Sorting Test than comparison subjects. Within patients with MA dependence, the subgroup of DRD2-TaqI A1 carrier had greater NS scores relative to those without, whereas there was only a trend level of lower frontal executive function in the first subgroup. CONCLUSION: In the present study, the MA-dependent patients with DRD2-TaqI A1 allele had significantly greater NS scores and lower frontal executive function with a trend level than those without. These preliminary results suggest that MA-dependent patients may have the possibility of genetic and biogenic vulnerability to MA.

Depression like characteristics of 5HTTLPR polymorphism and temperament in excessive internet users.

INTRODUCTION: Excessive internet use (EIU) has been reported to be comorbid with depression and the manifestation of its symptoms. This study examines the characteristics of excessive internet users that are similar to those of patients with depressive disorders in terms of serotonin transporter gene expression and harm avoidance. METHODS: 91 male adolescents with EIU and 75 healthy comparison subjects were recruited. Between group comparisons were made on genetic polymorphisms of the serotonin transport gene and with respect to novelty seeking and harm avoidance (HA) of Cloninger's Temperament Character Inventory. RESULTS: The homozygous short allelic variant of the serotonin transporter gene (SS-5HTTLPR) is more frequent in the EIU group (chi(2)=4.38, df=1, p<0.05). The HA and Beck Depression Inventory (BDI) scores were significantly higher in the EIU group than in the healthy comparison group (t=7.03, df=164, p<0.01; t=2.12, df=164, p=0.04). EIU subjects expressing SS-5HTTLPR also showed higher HA (HA1, HA2, HA4, and total HA) and Young's internet addiction scale scores than EIU subjects expressing the other serotonin transporter gene allele variants (t=2.47, df=89, p=0.01; t=2.33, df=89, p=0.02; t=2.17, df=89, p=0.03; t=2.25, df=89, p=0.03; t=2.93, df=89, p<0.01 respectively). CONCLUSIONS: The EIU group had higher SS-5HTTLPR frequencies, harm avoidance, and BDI scores. SS-5HTTLPR expression was closely related to harm avoidance in EIU. The results of this study suggest that EIU subjects may have genetic and personality traits similar to depressed patients.

Genetic polymorphisms of alcohol and aldehyde dehydrogenase, dopamine and serotonin transporters in familial and non-familial alcoholism.

One hundred and eleven male patients with alcohol dependence and 123 nonalcoholic healthy men were tested for the genetic polymorphisms of alcohol dehydrogenase 2 (ADH2), aldehyde dehydrogenase 2 (ALDH2), serotonin transporter (5-HTT) and dopamine transporter (DAT1). There were significant differences in genotype frequencies of ADH2 C992G and A13543G SNPs between alcoholic patients with family history of alcohol dependence (familial) and alcoholic patients without family history (non-familial). Genotype and allele frequencies of ALDH2 G1951A SNP in familial or non-familial alcoholic patients differ from normal controls. Neither 5-HTTLPR L/S nor DAT1 G2319A SNP genotypes nor alleles discriminated alcoholic patients from normal controls. These findings suggest that the genetic characteristics of alcohol metabolism in non-familial alcoholics fall between non-alcoholism and familial alcoholics.

Effects of catechol-O-methyltransferase Val158Met polymorphism on the cognitive stability and aggression in the first-onset schizophrenic patients.

We assessed catechol-O-methyltransferase (COMT) polymorphism in 132 first-onset schizophrenic patients and 80 healthy controls. The relationship between COMT polymorphism and cognitive function, aggression and psychiatric symptoms was tested in the schizophrenic group. COMTL carrier had higher digit span score and lower similarity score than COMTH homozygote. COMTL carrier had higher attention and delusion scores and lower inappropriate affect scores than COMTH homozygote. Attention and delusion scores of COMTL allele were higher than COMTH allele. COMTL group had higher aggression than COMTH homozygote. Our results support the theory that COMTL allele was related with increased tonic dopamine activity and cognitive 'stability', which may induce cognitive inflexibility in schizophrenia.

Effect of the apolipoprotein E epsilon4 allele on the efficacy and tolerability of galantamine in the treatment of Alzheimer's disease.

OBJECTIVE: To investigate the effect of the apolipoprotein E (ApoE) epsilon4 allele on the efficacy and tolerability of galantamine treatment. METHODS: A total of 202 patients with mild to moderate Alzheimer's disease participated in a 16-week, prospective, multi-center, randomized, double-blind galantamine trial in a Korean population. Patients were assessed at baseline and after 4, 8 and 16 weeks of randomized treatment using the 11-item cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog/11), the Clinician's Interview-Based Impression of Change plus Caregiver Input (CIBIC-plus), the Disability Assessment for Dementia Scale (DAD), the Behavioural Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD) and adverse events. ApoE genotypes were determined for all subjects. RESULTS: Of the 202 subjects, 115 carried at least one ApoE epsilon4 allele and 87 did not. In both ApoE epsilon4 carriers and ApoE epsilon4 noncarriers, significant improvements were detected relative to baseline on ADAS-cog/11, CIBIC-plus, DAD and BEHAVE-AD. ApoE epsilon4 noncarriers showed better improvement in mean total BEHAVE-AD score and mean psychosis (delusions and hallucinations) subscale score than ApoE epsilon4 carriers. The incidence of weight loss was significantly higher in ApoE epsilon4 carriers (n = 11; 9.6%) than in ApoE epsilon4 noncarriers (n = 1; 1.2%) during this 16-week study, even though 92% of patients who complained of weight loss completed this 16-week trial successfully. CONCLUSION: ApoE epsilon4 genotype does not affect galantamine-related improvements in cognition, global rating, function and behavior. Longer prospective studies with larger patient populations are required to confirm these new findings.