Alzheimer's disease (AD) is the most common neurodegenerative disorder, which features mainly with memory impairment as the initial symptom of progressive loss of cognitive function. Its main pathological changes include senile plaques and neurofibrillary tangles. The pathogenesis of AD is still unclear, though it may be connected with aging, genetic factors and environmental factors. Among these, aging and environmental factors can be modified by epigenetics. In this paper, advances in the study of epigenetic mechanisms related to the pathogenesis of AD are reviewed.
Alzheimer Disease ; genetics ; psychology ; Animals ; Cognition ; Epigenesis, Genetic ; Humans

BACKGROUND: Physical disability may result in some impairment of the score for Instrumental Activities of Daily Living (IADL). The aim of this study was to evaluate the effect of physical disability on IADL in patients with Alzheimer's disease (AD), amnestic mild cognitive impairment (aMCI), subcortical vascular dementia (SVD), and vascular mild cognitive impairment of the subcortical type (svMCI). METHODS: Fifty-six patients with AD, 30 with SVD, 27 with aMCI, and 21 with svMCI were recruited consecutively from a memory clinic. Informants for the subjects completed a Korean version of the IADL (K-IADL). In addition, the informants were asked to choose the cause of each dependent activity of K-IADL from the following: cognitive impairment, physical disability, or both. The cause of the physical disability was defined as being focal neurologic symptoms, other physical disease, or both. RESULTS: Compared to AD patients, SVD patients had higher K-IADL scores [2.02+/-0.80 (mean+/-SD) vs. 1.45+/-0.90, p<0.01] and focal neurologic signs (FNS; 8.0+/-5.8 vs. 0.0+/-0.0, p<0.001), and lower Barthel Index scores (14.7+/-5.1 vs. 19.6+/-1.2, p<0.001). Patients with svMCI had higher FNS (3.8+/-4.5 vs. 0.0+/-0.0, p<0.001) compared to those with aMCI. The most common cause of dependency of activities in K-IADL was cognitive impairment in AD, aMCI, and svMCI patients, and the combined effect of cognitive impairment and physical disability in those with SVD. The cause of physical disability was FNS in 96% of SVD patients and in all patients with svMCI. CONCLUSIONS: The effects of FNS as well as cognitive impairment should be considered when measuring the IADL of the patients with SVD or svMCI.
Activities of Daily Living ; Alzheimer Disease ; Dementia, Vascular ; Dependency (Psychology) ; Humans ; Memory ; Mild Cognitive Impairment ; Neurologic Manifestations

OBJECTIVE: Education is expected to have an effect on differential item functioning (DIF) on the 15-item Modified Boston Naming Test in the Korean version of the Consortium to Establish a Registry for Alzheimer's Disease Assessment Packet (BNT-KC). However, no study has examined DIF in the BNT-KC. METHODS: We used the item response theory to investigate the impact of education on the DIF in the BNT-KC among elderly individuals with or without dementia (n=720). A two-parameter item response model was used to determine the difficulty and discrimination parameters of each item. The Benjamini-Hochberg procedure was used to address the risk of Type I errors on multiple testing. RESULTS: Four items, “mermaid,”“acorn,”“compass,” and “pomegranate” continued to demonstrate DIF after controlling for multiple comparisons. Those with low education levels were more likely to error on “mermaid” and “compass,” while those with high education levels were more likely to error on “acorn” and “pomegranate.”“Hand” and “red pepper” were too easily identified to be used for detecting dementia patients. “Monk's hat” and “pomegranate” were less discriminating than other items, limiting their usefulness in clinical setting. CONCLUSION: These findings may provide useful information for the development of a revised version of the BNT-KC to help clinicians make diagnostic decisions more accurately.
Aged ; Alzheimer Disease ; Dementia ; Diagnostic Errors ; Discrimination (Psychology) ; Education* ; Humans ; Language Tests

BACKGROUND: The patterns of cognitive impairment in subcortical vascular dementia (SVaD) have been insufficiently investigated as compared with those in Alzheimer disease (AD). The aims of this study are to clarify the differences in the cognitive profiles between patients with SVaD and AD, and to differentiate between these two dementias using neuropsychological assessment. METHODS: Twenty-seven patients with SVaD, 45 patients with AD and 27 normal controls participated in this study. The dementia groups were all matched for age, education and the severity of dementia using the clinical dementia rating scale (CDR) and the global deterioration scale (GDS). All subjects were evaluated with a battery of detailed neuropsychological tests assessing attention, memory, language, visuospatial functions and frontal executive functioning. RESULTS: Both dementia patient groups demonstrated significant impairments in all cognitive domains including attention, verbal and visual memory, language function pertaining to naming, visuospatial and frontal executive functions compared with the control group. The patients with SVaD showed greater deficits in several items pertaining to attention and frontal executive functions than the AD patients. However, the AD group did not show any significant impairment in comparison with the SVaD group in any cognitive domain. CONCLUSIONS: It was concluded that patients with SVaD show different patterns of neurocognitive profiles from those with AD in the items of frontal executive dysfunctions and that quantitative neuropsychological assessments can play an important role in the discrimination between SVaD and AD.
Alzheimer Disease* ; Dementia ; Dementia, Vascular* ; Discrimination (Psychology) ; Education ; Executive Function ; Humans ; Memory ; Neuropsychological Tests ; Neuropsychology

The causes of mental disorders are complex, and early recognition and early intervention are recognized as effective way to avoid irreversible brain damage over time. The existing computer-aided recognition methods mostly focus on multimodal data fusion, ignoring the asynchronous acquisition problem of multimodal data. For this reason, this paper proposes a framework of mental disorder recognition based on visibility graph (VG) to solve the problem of asynchronous data acquisition. First, time series electroencephalograms (EEG) data are mapped to spatial visibility graph. Then, an improved auto regressive model is used to accurately calculate the temporal EEG data features, and reasonably select the spatial metric features by analyzing the spatiotemporal mapping relationship. Finally, on the basis of spatiotemporal information complementarity, different contribution coefficients are assigned to each spatiotemporal feature and to explore the maximum potential of feature so as to make decisions. The results of controlled experiments show that the method in this paper can effectively improve the recognition accuracy of mental disorders. Taking Alzheimer's disease and depression as examples, the highest recognition rates are 93.73% and 90.35%, respectively. In summary, the results of this paper provide an effective computer-aided tool for rapid clinical diagnosis of mental disorders.
Humans ; Mental Disorders/diagnosis* ; Alzheimer Disease/diagnosis* ; Brain Injuries ; Electroencephalography ; Recognition, Psychology

Objective: To construct and compare the dynamic prediction models of the risk of mild cognitive impairment (MCI) in the elderly based on six different cognitive function scales. Methods: Based on longitudinal data from the Alzheimer's Disease Neuroimaging Initiative from 2005 to 2020, Mini-mental state examination (MMSE), functional activities questionnaire (FAQ), Alzheimer's disease assessment scale-cognitive (ADAS-Cog) 11, ADAS-Cog13, ADAS delayed word recall (ADASQ4), and Rey auditory verbal learning test (RAVLT)_immediate were used as longitudinal cognitive function evaluation indicators to assess the longitudinal changes in cognitive function. The joint model was used to analyze association between indicators variation trajectory and survival outcome MCI, and construct the risk prediction model of MCI in the elderly, the linear mixed model was constructed the longitudinal sub-model which described the evolution of a repeated measure over time, a proportional hazards model was constructed the survival sub-model, and the two sub-models were connected through the correlation parameter (α). The areas under the receiver operator characteristic curve (AUC) were used to evaluate the predictive efficacy of the model in the follow-up period of (t, t+Δt). The starting point t was selected at the 30^th, 42^nd, and 54^th month, and the Δt was selected as 15 and 21 months. Based on the prediction model, an example of the research object was selected for dynamic individual predictions of the risk of MCI. Results: Finally, 544 older adults (aged 60 years and above) with normal baseline cognitive status were included, of which 119 cases (21.9%) had MCI during the follow-up process were regarded as the case group, and 425 cases remained normal as the control group. The joint model suggests that the longitudinal trajectories of the six evaluation indicators are all related to the risk of MCI (P<0.001). The risk of MCI decreased by 32.3% (HR=0.677, 95%CI: 0.541-0.846) and 10.8% (HR=0.892, 95%CI: 0.865-0.919) for each one-point increase of MMSE and RAVLT_immediate longitudinal scores. The risk of MCI increased by 53.2% (HR=1.532, 95%CI: 1.393-1.686), 36.2% (HR=1.362, 95%CI: 1.268-1.462), 23.2% (HR=1.232, 95%CI: 1.181-1.285), and 85.1% (HR=1.851, 95%CI:1.629-2.104) for each one-point increase of FAQ, ADAS-Cog11, ADAS-Cog13, and ADASQ4 longitudinal scores. AUC results show that RAVLT_immediate (0.760 2) and ADASQ4 (0.755 8) have higher average prediction efficiency, followed by ADAS-Cog13 (0.743 7), ADAS-Cog11 (0.715 3), FAQ (0.700 8) and MMSE (0.629 5). ADASQ4 joint model was used to provide a dynamic individual prediction of the risk of MCI. The average probability of MCI after five years of follow-up and ten years of follow-up in the example individuals were 8% and 40%, respectively. Conclusions: The RAVLT_immediate and ADASQ4 scales, which are only for memory tests, have high accuracy in predicting the risk of MCI. Using the RAVLT_immediate and ADASQ4 scales as longitudinal cognitive function evaluation indicators to construct a joint model, the results can provide a basis for realizing MCI risk prediction for the elderly.
Aged ; Alzheimer Disease/psychology* ; Cognition ; Cognitive Dysfunction/epidemiology* ; Humans ; Middle Aged ; Neuropsychological Tests ; Risk Factors

PURPOSE: To clarify the effects of missing values due to behavioral and psychological symptoms in dementia (BPSD) in Alzheimer's disease (AD) patients on the neuropsychological tests, this study describes the pattern of missing values due to BPSD, and its influence on tests. MATERIALS AND METHODS: Drug-naive probable AD patients (n=127) with BPSD and without BPSD (n=32) were assessed with Seoul Neuropsychological Screening Battery including measures of memory, intelligence, and executive functioning. Moreover, patients were rated on Korean Neuropsychiatry Inventory (K-NPI). RESULTS: The more severe the K-NPI score, the less neuropsychological tests were assessable, leading to many missing values. Patients with BPSD were more severely demented than those without BPSD. K-NPI scores were significantly correlated with the number of missing values. The effect of BPSD was largest for tests measuring frontal functions. The replacement of the missing values due to BPSD by the lowest observed score also showed the largest effect on tests of frontal function. CONCLUSION: The global cognitive and behavior scales are related with missing values. Among K-NPI sub-domains, delusion, depressing, apathy, and aberrant motor behavior are significantly correlated for missing values. Data imputation of missing values due to BPSD provides a more differentiated picture of cognitive deficits in AD with BPSD.
Aged ; Alzheimer Disease/*psychology ; Behavioral Symptoms ; Cognition ; Delusions ; Dementia/psychology ; Female ; Humans ; Male ; Neuropsychological Tests ; Regression Analysis

INTRODUCTIONHyperfamiliarity, a phenomenon in which feelings of familiarity are evoked by novel stimuli, is well described in epilepsy and the lesioned brain. Abnormality of familiarity in Alzheimer's disease (AD) and mild cognitive impairment (MCI) have also been described in the literature, but more from a neuropsychological approach perspective. Currently, there is a lack of study on the real-life experience of familiarity abnormality in dementia and MCI. Our aim was to compare the occurrence of hyperfamiliarity among dementia and MCI.

MATERIALS AND METHODSWe recruited 73 participants, 29 with AD, 10 with vascular dementia, 7 with MCI and 27 healthy controls, and administered a questionnaire to assess hyperfamiliarity frequency.

RESULTSHyperfamiliarity was observed in real-life in cognitive impairment, but was unrelated to its severity or underlying aetiology.

CONCLUSIONThis study highlights the similar rate of occurrence of hyperfamiliarity in the daily life of individuals with cognitive impairment. Future research should examine neuropsychological correlations and mechanisms that contribute to such observations.

Aged ; Aged, 80 and over ; Alzheimer Disease ; physiopathology ; psychology ; Case-Control Studies ; Cognitive Dysfunction ; physiopathology ; psychology ; Dementia ; physiopathology ; psychology ; Dementia, Vascular ; physiopathology ; psychology ; Female ; Humans ; Male ; Middle Aged ; Recognition (Psychology) ; Severity of Illness Index ; Singapore

BACKGROUND AND PURPOSE: Previously developed Korean versions of the Trail Making Test (TMT) that replaced the English in part B, has been unsuccessful in Korea. The current study identifies the type of TMT tasks from the among multiple TMT versions, which practically and accurately detects the stage of cognitive decline. METHODS: We applied five TMT versions, which include the original TMT, TMT-Korean letter (TMT-KL), TMT-Korean consonant (TMT-KC), TMT-black and white (TMT-B&W), and TMT-square and circle (TMT-S&C). A total of 168 participants were enrolled: 42 cognitively normal controls (NC), 72 patients with mild cognitive impairment (MCI), and 54 patients with Alzheimer's disease (AD). Two sets of TMT (set "A" including TMT, TMT-KL and TMT-B&W, and set "B" including TMT, TMT-KC, and TMT-S&C) were randomly administered to subjects within the contact of a fixed neuropsychological battery. RESULTS: The completion times of TMT-B and TMT-B&W successfully distinguished NC from MCI and AD. TMT-B&W also showed a high correlation with other neuropsychological tests, and correlated well with the original TMT. The other TMT were frequently not successfully completed, nor could they differentiate the clinical groups. CONCLUSIONS: Among the five TMT tasks, the original TMT and the TMT-B&W appeared to be most sensitive to the degree of cognitive impairment. TMT-B&W showed a pattern consistent with the original TMT; thus, this measure may be optimal in Korean older adults, where familiarity with the English alphabet is questionable.
Adult ; Aged* ; Alzheimer Disease ; Cognition Disorders ; Humans ; Korea ; Mild Cognitive Impairment ; Neuropsychological Tests ; Recognition (Psychology) ; Trail Making Test*

OBJECTIVETo evaluate distribution and influence factors of logic memory (LM) modified in assessing and scoring method in normal population and Alzheimer's disease (AD) patients, and definite the cut-off point of the modified scale.

METHODSTotally 183 AD patients, including 118 mild and 65 moderate in degree, 1,417 controls, including 1,283 normal individuals and 134 individuals suffered from other diseases, were recruited in this study. Modified LM was conducted.

RESULTSEducational level (F=354.36, STB=0.46, P=0.0001) was the most obvious factor in demographic data to influence total score in normal control group by a fitting of multiple regression models. The total score increased with the rising of educational level in normal controls (P=0.0001) and other diseases controls (P=0.0001), but not in AD cases (P=0.1365). The total scores were significantly different among normal controls (20.2 +/- 0.2), other diseases controls (17.5 +/- 0.5), mild AD patients (9.6 +/- 0.5) and moderate AD patients (7.1 +/- 0.7) (P=0.0001, P=0.0059), after adjusted educational level, age, sex and rural/urban status by multiple analysis covariance. The sensitivity of cut-off points using modified methods to diagnose AD reasonably increased to 71.98%, while the specificity was 94.11%. According to the sum of long-delayed recall and long-delayed recognition, the sensitivity increased with the rising of educational levels. For education levels at illiteracy, elementary school, junior middle school, senior middle school and above senior middle school, the cut-off points for total score of modified method were 6.5, 9.5, 10.8, 13 and 15.8, respectively, and for sum of long-delayed recall and long-delayed recognition the cut-off points were 5, 6, 8, 9, 10.

CONCLUSIONSWhen modified LM used as a neuropsychological assessment, it is with high specificity, high accuracy and reasonable sensitivity. It is suitable for the diagnosis of AD in early stages, especially for individuals with high educational levels.

Aged ; Alzheimer Disease ; diagnosis ; psychology ; Educational Status ; Female ; Humans ; Intelligence Tests ; Male ; Memory ; physiology ; Middle Aged ; Neuropsychological Tests ; Sensitivity and Specificity