The pathophysiologic process of Alzheimer's disease (AD) begins years before the diagnosis of clinical dementia. This concept of preclinical AD has arisen from the observation of AD pathologic findings such as senile plaques and neurofibrillary tangles in the brains of people who at the time of death had normal cognitive function. Recent advances in biomarker studies now provide the ability to detect the pathologic changes of AD, which are antecedent to symptoms of the illness, in cognitively normal individuals. Functional and structural brain alterations that begin with amyloid-beta accumulation already show the patterns of abnormality seen in individuals with dementia due to AD. The presence of preclinical AD provides a critical opportunity for potential interventions with disease-modifying therapy. This review focuses on the studies of antecedent biomarkers for preclinical AD.
Aging ; Alzheimer Disease ; Biomarkers ; Brain ; Dementia ; Neurofibrillary Tangles ; Plaque, Amyloid

BACKGROUND: The early stage of Alzheimer disease might show early memory impairment with normal general cognitive function. Our study aimed to investigate elderly with normal Korean version of mini-mental state examination (K-MMSE) score and recall score of 0 for 1 year. We predicted that the patients would show different characteristics and would progress more rapidly compared with normal controls. METHODS: This study was based on the data from complete enumeration survey of Mapo-gu Regional Center for Dementia in 2009. We divided all subjects into three groups: subjects with normal K-MMSE scores and recall score of 0 were group 1-1 (n=152), subjects with abnormal K-MMSE scores were group 1-2 (n=64) and subjects with normal K-MMSE scores and recall score of 1 to 3 were group 1-3 (n=941). We compared basic demographics and social characteristics among the three groups. After 1 year (2010), the subjects in group 1-1 (90 out of 152) underwent follow-up examinations for dementia diagnosis. They were also divided into three groups (2-1, 2-2, 2-3) according to K-MMSE and recall scores. RESULTS: Group 1-1 showed different baseline characteristics compared with normal controls. After 1 year, 25.5% (23 out of 90) of the group 2-1 were diagnosed as mild cognitive impairment (n=16) or dementia (n=7). CONCLUSION: Our study suggested that subjects with normal K-MMSE scores but recall score of 0 are not entirely "normal". Further detailed evaluation might be needed if memory impairment is suspicious although the K-MMSE scores are within normal range.
Aged* ; Alzheimer Disease ; Dementia* ; Demography ; Diagnosis* ; Follow-Up Studies* ; Humans ; Memory ; Mild Cognitive Impairment ; Pilot Projects* ; Reference Values ; Sociology

BACKGROUND: Cultural characteristics of taking care of patients with dementia in Korea are based on the influence of Confucianism on the lifestyle of Koreans. In addition, as the family size has been getting smaller, the number of old persons who live alone has been increasing. The purpose of this study is to examine the proportion of the elderly with dementia who live alone and demographics of caregivers when such patients live with their family. METHODS: From the multiple hospital-based cohort, 973 elderly patients with very mild dementia (Clinical Dementia Rating [CDR]=0.5), 1,056 patients with mild dementia (CDR=1) and 359 patients with moderate dementia (CDR=2) were recruited. We analyzed the proportion of the patients with dementia who live alone and the demographics of the caregivers if such patients live with and are taken care of by such caregivers depending upon the severity of dementia. RESULTS: The proportion of the patients with dementia who live alone accounts for about 40% of all elderly patients with dementia. Major age groups of caregivers are of 40s and 50s. Sons, daughters, and spouses were ranked in the said order in the proportion of caregivers according to their relationship to patients. CONCLUSIONS: Up to now, family members care for about 60% of elderly patients with dementia, which may suggest that from the objective viewpoint, direct burden borne by caregivers for old patients with dementia would be considerably high. On the other hand, about 40% of dementia patients live alone, implying that the social care system is needed for them.
Aged ; Caregivers ; Cohort Studies ; Confucianism ; Cultural Characteristics ; Dementia ; Demography ; Family Characteristics ; Hand ; Humans ; Korea ; Life Style ; Nuclear Family ; Spouses

BACKGROUND: Cultural characteristics of taking care of patients with dementia in Korea are based on the influence of Confucianism on the lifestyle of Koreans. In addition, as the family size has been getting smaller, the number of old persons who live alone has been increasing. The purpose of this study is to examine the proportion of the elderly with dementia who live alone and demographics of caregivers when such patients live with their family. METHODS: From the multiple hospital-based cohort, 973 elderly patients with very mild dementia (Clinical Dementia Rating [CDR]=0.5), 1,056 patients with mild dementia (CDR=1) and 359 patients with moderate dementia (CDR=2) were recruited. We analyzed the proportion of the patients with dementia who live alone and the demographics of the caregivers if such patients live with and are taken care of by such caregivers depending upon the severity of dementia. RESULTS: The proportion of the patients with dementia who live alone accounts for about 40% of all elderly patients with dementia. Major age groups of caregivers are of 40s and 50s. Sons, daughters, and spouses were ranked in the said order in the proportion of caregivers according to their relationship to patients. CONCLUSIONS: Up to now, family members care for about 60% of elderly patients with dementia, which may suggest that from the objective viewpoint, direct burden borne by caregivers for old patients with dementia would be considerably high. On the other hand, about 40% of dementia patients live alone, implying that the social care system is needed for them.
Aged ; Caregivers ; Cohort Studies ; Confucianism ; Cultural Characteristics ; Dementia ; Demography ; Family Characteristics ; Hand ; Humans ; Korea ; Life Style ; Nuclear Family ; Spouses

Subjective memory impairment (SMI) is now increasingly recognized as a risk factor of progression to dementia. This study investigated gray and white matter changes in the brains of SMI patients compared with normal controls and mild cognitive impairment (MCI) patients. We recruited 28 normal controls, 28 subjects with SMI, and 29 patients with MCI aged 60 or older. We analyzed gray and white matter changes using a voxel-based morphometry (VBM), hippocampal volumetry and regions of interest in diffusion tensor imaging (DTI). DTI parameters of corpus callosum and cingulum in SMI showed more white matter changes compared with those in normal controls, they were similar to those in MCI except in the hippocampus, which showed more degenerations in MCI. In VBM, SMI showed atrophy in the frontal, temporal, and parietal lobes compared with normal controls although it was not as extensive as that in MCI. Patients with SMI showed gray and white matter degenerations, the changes were distinct in white matter structures. SMI might be the first presenting symptom within the Alzheimer's disease continuum when combined with additional risk factors and neurodegenerative changes.
Aged ; Brain/*pathology ; Diagnosis, Differential ; Diffusion Tensor Imaging/methods ; Female ; Gray Matter/*pathology ; Humans ; Male ; Memory Disorders/*diagnosis/etiology ; Mild Cognitive Impairment/complications/*diagnosis ; Neurodegenerative Diseases/complications/*pathology ; Reference Values ; Reproducibility of Results ; Sensitivity and Specificity ; White Matter/*pathology

Purpose: We compared the feasibility of quantitative analysis methods using bone SPECT/CT with those using planar bone scans to assess active sacroiliitis. Methods: We retrospectively reviewed whole-body bone scans and pelvic bone SPECT/CTs of 8 patients who had clinically confirmed sacroiliitis and enrolled 24 patients without sacroiliitis as references. The volume of interest of each sacroiliac joint, including both the ilium and sacrum, was drawn. Active arthritis zone (AAZ) was defined as the zone of voxels with higher SUV than sacral mean SUV within the VOI of SI joint. Then, the following SPECT/CT quantitative parameters, SUVmax (maximum SUV), SUV50% (mean SUV in highest 50% of SUV), and SUV-AAZ, and the ratio of those values to sacral mean SUV (SUVmax/S, SUV50%/S, SUV-AAZ/S) were calculated. For the planar bone scan, the mean count ratio of SI joint/sacrum (SI/S) was conventionally measured. Results: Most of the SPECT/CT parameters of the sacroiliitis group were significantly higher than the normal group, whereas SI/S of the planar bone scan was not significantly different between the two groups. In receiver operating characteristic curve analysis, SUV-AAZ/S showed the highest AUC of 0.992, followed by SUV50%/S and SUVmax/S. All ratio parameters of the SPECT/CT showed higher AUC values than the SUV parameters of SI joint or SI/S of the planar scan. Conclusions The quantitative analyses of bone SPECT/CT showed better performance in assessing active sacroiliitis than the planar bone scan. SPECT/CT parameters using the ratio of the SI joint to sacrum showed more favorable results than SUV parameters such as SUVmax, SUV50%, and SUV-AAZ.

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.
Brain Stem ; Cerebrovascular Circulation ; Clinical Study ; Cognition ; Dizziness ; Erectile Dysfunction ; Humans ; Male ; Methylenebis(chloroaniline) ; Mild Cognitive Impairment ; Myalgia ; Parietal Lobe ; Perfusion ; Phosphodiesterase Inhibitors ; Prospective Studies ; Somatosensory Cortex ; Tadalafil ; Tomography, Emission-Computed

BACKGROUND: The verbal fluency test consists of two separate tests of semantic fluency and phonemic fluency. The performance patterns of these tests differ with the type of dementia. We studied the patterns of verbal fluency between Alzheimer's disease (AD) and subcortical vascular dementia (SVaD), and assessed the clinical utility of these tests. METHODS: The 1,475 selected participants comprised 73 normal control subjects, 673 patients with amnestic mild cognitive impairment (aMCI), 535 AD patients, 42 patients with subcortical vascular mild cognitive impairment (svMCI), and 152 SVaD patients. We analyzed the z-score for the total number of animal items as a semantic fluency index and the z-score of the phonemic total score as a phonemic fluency index. RESULTS: The performance of semantic fluency was lower than that of phonemic fluency in all groups. The SVaD group showed the worst scores and abnormal performances on both tests, while the AD group presented abnormal performance only for semantic fluency. Dividing the patients with dementia according to severity revealed a different pattern between AD and SVaD for the clinical dementia rating (CDR) stage of 0.5. The performance of the AD group declined gradually with CDR. However, the SVaD group performed very poorly in both tests even for very mild dementia (CDR stage of 0.5). The aMCI and svMCI groups exhibited similar performance patterns. CONCLUSIONS: The pattern of semantic and phonemic fluency was not clinically useful at the MCI stage, but it could be helpful in differentiating AD and SVaD in the early stage of dementia.
Alzheimer Disease* ; Animals ; Dementia* ; Dementia, Vascular* ; Humans ; Mild Cognitive Impairment ; Semantics ; Task Performance and Analysis*

BACKGROUND AND PURPOSE: The Literacy-Independent Cognitive Assessment (LICA) has been developed for a diagnosis of dementia and is a useful neuropsychological test battery for illiterate populations as well as literate populations. The objective of this study was to develop the short form of the LICA (S-LICA) and to evaluate the reliability and validity of the S-LICA. METHODS: The subtests of the S-LICA were selected based on the factor analysis and validation study results of the LICA. Patients with dementia (n=101) and normal elderly controls (n=185) participated in this study. RESULTS: Cronbach's coefficient alpha of the S-LICA was 0.92 for illiterate subjects and 0.94 for literate subjects, and the item-total correlation ranged from 0.63 to 0.81 (p<.01).The test-retest reliability of the S-LICA total score was high (r=0.94, p<.001), and the subtests had high test-retest reliabilities (r=0.68-0.87, p<.01). The correlation between the K-MMSE and S-LICA total scores were substantial in both the illiterate subjects (r=0.837, p<.001) and the literate subjects(r=0.802, p<.001). The correlation between the S-LICA and LICA was very high (r=0.989, p<.001). The area under the curve of the receiver operating characteristic was 0.999 for the literate subjects and 0.985 for the illiterate subjects. The sensitivity and specificity of the S-LICA for a diagnosis of dementia were 97% and 96% at the cutoff point of 72 for the literate subjects, and 96% and 93% at the cutoff point of 68 for the illiterate subjects, respectively. CONCLUSIONS: Our results indicate that the S-LICA is a reliable and valid instrument for quick evaluation of patients with dementia in both illiterate and literate elderly populations.
Aged ; Dementia ; Literacy ; Humans ; Neuropsychological Tests ; Reproducibility of Results ; ROC Curve ; Sensitivity and Specificity

BACKGROUND: The interlocking pentagon drawing test, a part of the Mini-Mental State Examination (MMSE), is a widely used clinical practice to measure visuoconstructional ability of dementia patients. We investigated the anatomical structures of brain associated with pentagon drawing in subjects with mild to moderate Alzheimer's disease (AD) by using voxel-based morphometry (VBM). METHODS: Medical records of forty-four AD patients were reviewed and a 1.5 T SPGR 3D image data were used for VBM analysis. A voxel-based multiple regression analysis was used to investigate correlation between gray matter loss and pentagon drawing performance of AD patients. The correlations between pentagon drawing score and MMSE score were evaluated by Spearman correlation analysis. RESULTS: There was a positive correlation between the interlocking pentagon copying scores and the MMSE scores (r=0.448, p=0.002). The lower the scores of interlocking pentagon copying were, the more severe the atrophy of right inferior frontal gyrus became ([x, y, z]=[52, 39, 3], Broadmann area 45, and z score=3.86). CONCLUSIONS: The performance of interlocking pentagon drawing is associated with a general cognitive function in patients with mild-to-moderate Alzheimer's disease. It is also associated with the atrophy of the right inferior frontal gyrus.
Alzheimer Disease ; Atrophy ; Brain ; Coat Protein Complex I ; Dementia ; Humans ; Medical Records