BACKGROUND: Estrogen deficiency is linked to cardiovascular disease (CVD) and osteoporosis in women. Ovarian hormones are also presumed to play a key role in Alzheimer's disease (AD). This study was designed to investigate the clinical evidences of estrogen deficiency and therapeutic efficacy of hormone replacement (HRT) in women with AD. METHODS: Clinical tests indicative of ovarian insufficiency were performed in 44 female patients with AD (age: 49-81: 68.0+1.2, Mean+SEM). Out of 40 patients treated with HRT, 16 completed one-year follow-ups. Modification of risk factors for CVD and changes in bone mineral density with HRT were assessed. Periodic MMSE was performed to evaluate changes in cognitive function under HRT. RESULTS: All the patients except two were postmenopausal, and years since menopause were 18.2+1.8. Six patients had early menopause. Hypertension was detected in 9 patients, and one had history of CVD. Prevalence of osteoporosis at lumbar vertebrae or femur neck and that of fragility fracture were 57% and 39%, respectively. Sixteen patiens who completed one-year HRT were analyzed separately: HRT reduced significantly blood levels of total cholesterol, Lp(a), and glucose and increased HDL-cholesterol. HRT also prevented bone loss at both lumbar spine and femur neck. MMSE scores at 3, 6, and 12 months of HRT revealed no significant decline compared with baseline score. CONCLUSIONS: Female AD is late problem after menopause, and frequently associated with osteoporosis. In addition to beneficial modification of risk factors for CVD and prevention of further bone loss, HRT might inhibit cognitive decline assessed by MMSE in AD.
Alzheimer Disease* ; Bone Density ; Cardiovascular Diseases ; Cholesterol ; Dementia ; Estrogens ; Female ; Femur Neck ; Follow-Up Studies ; Glucose ; Hormone Replacement Therapy* ; Humans ; Hypertension ; Lumbar Vertebrae ; Menopause ; Osteoporosis ; Prevalence ; Risk Factors ; Spine

OBJECTIVE: Caregivers for patients with Alzheimer's disease (AD) suffer from psychological and financial burdens. However, the results of the relationship between burden and cognitive function, performance of activities of daily living, and depressive symptoms have remained inconsistent. Therefore, the aim of this study was to examine which factors are more significant predictors of heightened burden, cognitive impairment or functional decline, besides neuropsychiatric symptoms. METHODS: A cross-sectional study was conducted in a sample comprised of 1,164 pairs of patients with AD and caregivers from the Clinical Research of Dementia of South Korea study cohorts. The cognitive function of each sub-domain, functional impairments, depressive symptoms, and caregiver burden were assessed using the dementia version of Seoul Neuropsychological Screening Battery (SNSB-D), Barthel Index for Daily Living Activities (ADL), Seoul-Instrumental Activities of Daily Living (S-IADL), the Clinical Dementia Rating Sum of Box (CDR-SB), the Global Deterioration Scale (GDS), the Korean version of the Neuropsychiatric Inventory (K-NPI), and the 15-item Geriatric Depression Scale. RESULTS: We found that higher severity (higher CDR-SB and GDS scores) and more functional impairment (lower ADL and higher S-IADL scores) were significantly associated with higher caregiver burden. In addition, depressive symptoms of patients (higher Geriatric Depression Scale scores) were associated with higher caregiver burden. CONCLUSION: Therefore, interventions to help maintain activities of daily living in patients with AD may alleviate caregiver burden and improve caregiver well-being.
Activities of Daily Living ; Alzheimer Disease* ; Caregivers* ; Cognition ; Cohort Studies ; Cross-Sectional Studies ; Dementia ; Depression ; Humans ; Korea ; Mass Screening ; Seoul

Purpose: Brain metastases from renal cell carcinoma (RCC) have been successfully treated with stereotactic radiosurgery (SRS). Metastases to extra-cranial sites may be treated with similar success using stereotactic body radiation therapy (SBRT), where image-guidance allows for the delivery of precise high-dose radiation in a few fractions. This paper reports the authors’ initial experience with image-guided SBRT in treating primary and metastatic RCC. Materials and methods: The image-guided Brainlab Novalis stereotactic system was used. Fourteen patients with 23 extra-cranial metastatic RCC lesions (orbits, head and neck, lung, mediastinum, sternum, clavicle, scapula, humerus, rib, spine and abdominal wall) and two patients with biopsy-proven primary RCC (not surgical candidates) were treated with SBRT (24-40 Gy in 3-6 fractions over 1-2 weeks). All patients were immobilised in body cast or head and neck mask. Image-guidance was used for all fractions. PET/CT images were fused with simulation CT images to assist in target delineation and dose determination. SMART (simultaneous modulated accelerated radiation therapy) boost approach was adopted. 4D-CT was utilised to assess tumour/organ motion and assist in determining planning target volume margins. Results: Median follow-up was nine months. Thirteen patients (93%) who received SBRT to extra-cranial metastases achieved symptomatic relief. Two patients had local progression, yielding a local control rate of 87%. In the two patients with primary RCC, tumour size remained unchanged but their pain improved, and their renal function was unchanged post SBRT. There were no significant treatment-related side effects. Conclusion: Image-guided SBRT provides excellent symptom palliation and local control without any significant toxicity. SBRT may represent a novel, non-invasive, nephron-sparing option for the treatment of primary RCC as well as extra-cranial metastatic RCC.

OBJECTIVES: This study investigated the association between extrapyramidal signs (EPS) and five cognitive sub-domains in a large number of patients with mild cognitive impairment (MCI). METHODS: Our analyses considered 1,943 patients with MCI drawn from the nationwide Clinical Research of Dementia of South Korea study. EPS were defined as presence in patients with at least 1 of 11 operationally specified features. We assessed five cognitive sub-domains : attention, language, visuospatial function, memory, and frontal/executive function using the Seoul Neuropsychological Screening Battery-Dementia version. The associations of EPS with each cognitive sub-domain were analyzed with a multiple linear regression model after controlling for confounding factors : sex, age, education years, diabetes, hypertension, severity of global function, depressive symptoms, and white matter hyperintensities (WMH). RESULTS: 138 MCI patients (7.1%%) had EPS. This group had more global cognitive deterioration and severe WMH. MCI patients with EPS showed lower performance compared to those without EPS in 3 cognitive sub-domains: attention (p=0.05), visuospatial function (p=0.02), and frontal/executive function (p<0.0001). The language sub-domain and the memory sub-domain did not differ between the EPS positive and the EPS negative groups. CONCLUSION: EPS in MCI are associated with greater cognitive impairment in specific functional sub-domains rather than with global greater cognitive deterioration.
Cognition ; Dementia* ; Depression ; Education ; Humans ; Hypertension ; Korea* ; Linear Models ; Mass Screening ; Memory ; Mild Cognitive Impairment* ; Seoul

OBJECTIVES: We aimed to investigate the prevalence of Extrapyramidal signs (EPS) and the associations between EPS and cognitive subdomains in patients with Alzheimer disease (AD). METHODS: We recruited 1,324 patients with AD from the Clinical Research of Dementia of South Korea (CREDOS), a hospital based cohort study with fifty-six participating hospitals. We estimated cognitive subdomain using the Seoul Neuropsychological Screening Battery-Dementia version (SNSB-D). Dementia severity was measured by Clinical Dementia Rating Sum of Boxes (CDR-SB) and Korean version of Mini-Mental Status Examination (K-MMSE). The EPS group was defined by the presence of at least one EPS based on a focused neurologic examination. RESULTS: The prevalence of patients with EPS was 11%. These had higher CDR-SB scores than non-EPS group. After controlling for demographic, radiological, and dementia severity (CDR-SB) factors, EPS group showed lower cognitive ability in the subdomains for visuospatial and frontal-executive function than non-EPS group. The patients with EPS were showed significantly higher scores in the subdomain for memory function. CONCLUSION: The presence of EPSs in patients with AD was associated with lower visuospatial, frontal-executive function and higher memory function.
Alzheimer Disease ; Cohort Studies ; Dementia ; Humans ; Mass Screening ; Memory ; Neurobehavioral Manifestations ; Prevalence ; Republic of Korea

OBJECTIVE: Extrapyramidal signs (EPS) are common in patients with mild cognitive impairment (MCI). However, few studies have assessed the effect of EPS on the clinical course of MCI. We aimed to evaluate whether patients with EPS show more frequent progression from MCI to Alzheimer's disease (AD) and to other types of dementia. METHODS: Participants (n=882) with MCI were recruited, and were followed for up to 5 years. The EPS positive group was defined by the presence of at least one EPS based on a focused neurologic examination at baseline. RESULTS: A total of 234 converted to dementia during the follow-up period. The risk of progression to AD was lower in the patients with EPS after adjusting for potential confounders [hazard ratio (HR)=0.70, 95% confidence interval (CI)=0.53–0.93, p=0.01]. In contrast, the patients with EPS had a six-fold elevated risk of progression to dementia other than AD (HR=6.33, 95%CI=2.30–17.39, p < 0.001). CONCLUSION: EPS in patients with MCI is a strong risk factor for progression of MCI to non-Alzheimer dementia. The careful neurologic examination for EPS in patients with MCI can yield important clinical information for prognosis.
Alzheimer Disease ; Dementia* ; Follow-Up Studies ; Humans ; Korea* ; Mild Cognitive Impairment* ; Neurologic Examination ; Prognosis ; Risk Factors

OBJECTIVE: This study aimed to find the sex differences of the way how educational attainment influence on cognitive function in the mild cognitive impairment patients. METHODS: A total of 1,704 patients were recruited from a large hospital-based multi-center cohort. Cognitive subdomains were evaluated using the Seoul Neuropsychological Screening Battery-Dementia version. We employed multiple linear regression analysis to compare the score of cognitive subdomains between the groups with high versus low educational attainment based on the high school graduate. Interaction between educational attainment and sex was also included in the analysis RESULTS: High and low educational attainment group had 41.2% and 58.8% of patients in the study population. In the multiple regression analysis, score of all cognitive subdomains were significantly higher in the high educational attainment group. The score of attention, language, and visuospatial function were also significantly affected by interaction between educational attainment and sex. CONCLUSION: In the female patients, educational attainment showed higher influence on the attention, language, and visuospatial function score.
Cognition ; Cognitive Reserve ; Cohort Studies ; Dementia* ; Education* ; Female ; Humans ; Korea* ; Linear Models ; Mass Screening ; Mild Cognitive Impairment* ; Seoul ; Sex Characteristics

OBJECTIVE: The aim of this study was to investigate the association between cognitive subdomains and insight into one's cognitive impairment in patients with Alzheimer disease (AD). METHODS: We recruited 1,722 patients with AD from the Clinical Research of Dementia of South Korea study and designed a cross-sectional study. Each patient's cognitive subdomain was assessed by using the Seoul Neuropsychological Screening Battery-Dementia version. Severity of dementia was evaluated by Korean version of Mini-Mental Status Examination (K-MMSE) and Clinical Dementia Rating Sum of Boxes (CDR-SB). Insight into one's cognitive impairment was categorized as 'with insight' and 'without insight' through interview with patient's caregivers. RESULTS: Among the 1,722 patients with AD, 1,475 patients were included in the 'with insight' group and the remaining 247 patients were included in the 'without insight' group. Subjects in the 'without insight' group had lower K-MMSE and CDR-SB scores than those in the 'with insight' group. After controlling for demographic data and dementia severity, higher scores on both attention function (odds ratio=1.12, 95% confidence interval : 1.03-1.21) and frontal-executive function (odds ratio=1.03, 95% confidence interval : 1.01-1.05) significantly predicted the membership to 'with insight' group. CONCLUSION: In patients with AD, attention and frontal-executive function were associated with insight into one's cognitive impairment.
Alzheimer Disease* ; Caregivers ; Cross-Sectional Studies ; Dementia* ; Humans ; Korea ; Mass Screening ; Seoul

OBJECTIVE: Patients with mild cognitive impairment (MCI) are at high risk for dementia. Excessive alcohol consumption is known to adversely affect cognitive function. This study aimed to investigate the relationship between alcohol consumption and the risk for dementia in a cohort of MCI patients. METHODS: Participants (n=416) with (MCI) who met Petersen's criteria were recruited from a nationwide, prospective cohort study of dementia and were followed for a median of 17.52 months (range 5.4-63.48). Alcohol consumption was evaluated at baseline. RESULTS: One hundred twenty seven individuals (30.5%) developed incident dementia (115 Alzheimer disease) during follow-up. Patients with current alcohol consumption at baseline had a higher rate of progression to Alzheimer's dementia than those without current alcohol consumption (hazard ratio 1.61 ; 95% confidence interval 1.03 to 2.53). CONCLUSION: Alcohol consumption may increase the risk of progression to Alzheimer's dementia in patients with MCI.
Alcohol Drinking* ; Alzheimer Disease ; Cohort Studies ; Dementia* ; Follow-Up Studies ; Humans ; Korea ; Mild Cognitive Impairment* ; Prospective Studies ; Risk Factors*

OBJECTIVE: We aimed to find the sex differences of the way how educational attainment influence on cognitive function in patients with Alzheimer's disease (AD). METHODS: We recruited 424 patients with AD from a large hospital-based multi-center cohort. We evaluated cognitive subdomains using the Seoul Neuropsychological Screening Battery-Dementia version. We employed multiple linear regression analysis to compare the score of cognitive subdomains between the groups with high versus low educational attainment based on the high school graduate. Interaction between educational attainment and sex was also included in the analysis. RESULTS: High and low educational attainment group had 33.0% and 67.0% of patients in the study population. In the multiple regression analysis, score of all cognitive subdomains were significantly higher in the high educational attainment group. The score of attention was also significantly affected by interaction between educational attainment and sex. This result may be helpful to develop cognitive intervention therapy. CONCLUSION: In the female patients with AD, educational attainment showed higher influence on the attention score.
Alzheimer Disease* ; Cognition ; Cohort Studies ; Dementia* ; Education* ; Female ; Humans ; Korea* ; Linear Models ; Mass Screening ; Seoul ; Sex Characteristics