BACKGROUNDPatients with Alzheimer's disease (AD) manifest progressive decline in writing abilities. Most studies on agraphia in AD have been performed in the alphabetic system, such as English. However, these findings may not be applicable to other written language systems. The unique features of the Chinese written script could affect the patterns of agraphia in Chinese AD patients. The aim of this study was to explore the features of writing errors in Chinese patients with AD and amnestic mild cognitive impairment (a-MCI), as well as to study the relationship between their writing errors and neuropsychological functions.

METHODSIn this study, we performed an observational study in a group of subjects including 17 AD patients, 14 patients with a-MCI, and 16 elderly healthy controls. We analyzed the writing errors in these subjects and also studied the relationship between their writing errors and neuropsychological functions.

RESULTSOur study showed that in patients whose mother tongue is Chinese, writing ability was comparatively well preserved in the MCI phase but significantly impaired when the disease progressed to the stage of AD. The writing errors showed corresponding increase with the severity of cognition decline, both in the types of errors and rate of occurrence. Analysis of the writing errors showed that word substitution and unintelligible words were the most frequent error types that occurred in all the three study groups. The occurrence rate of unintelligible words was significantly higher in the AD group compared with the a-MCI group (P = 0.024) and control group (P = 0.018). In addition, the occurrence rates of word substitution were also significantly higher in AD (P = 0.013) and a-MCI groups (P = 0.037) than that of control group. However, errors such as totally no response, visuospatial impairment, paragraph agraphia, ideograph, and perseverative writing errors were only seen in AD group. Besides, we also found a high occurrence rate of visuoconstructional errors (13.3%) in our AD group.

CONCLUSIONSOur study confirmed that agraphia is an important feature in patients with AD. The writing error profile in patients whose native language is Chinese was unique compared to patients using the alphabetic language system.

Aged ; Agraphia ; diagnosis ; physiopathology ; Alzheimer Disease ; complications ; physiopathology ; Asian Continental Ancestry Group ; Cognition Disorders ; diagnosis ; physiopathology ; Cognitive Dysfunction ; diagnosis ; physiopathology ; Female ; Humans ; Male ; Middle Aged ; Neuropsychological Tests

To investigate inter- and intra-hemispheric electroencephalography (EEG) coherence at rest and during photic stimulation of patients with Alzheimer's disease (AD). Thirty-five patients (12 males, 23 females; 52 to approximately 64 y) and 33 sex- and age-matched controls (12 males, 21 females; 56 to approximately 65 y) were recruited in the present study. EEG signals from C3-C4, P3-P4, T5-T6 and O1-O2 electrode pairs resulted from the inter-hemispheric action, and EEG signals from C3-P3, C4-P4, P3-O1, P4-O2, C3-O1, C4-O2, T5-O1 and T6-O2 electrode pairs resulted from the intra-hemispheric action. The influence of inter- and intra-hemispheric coherence on EEG activity with eyes closed was examined, using fast Fourier transformation from the 16 sampled channels. The frequencies of photic stimulation were fixed at 5, 10 and 15 Hz, respectively. The general decrease of AD patients in inter- and intra-hemispheric EEG coherence was more significant than that of the normal controls at the resting EEG, with most striking decrease observed in the alpha-1 (8.0-9.0 Hz) and alpha-2 (9.5-12.5 Hz) bands. During photic stimulation, inter- and intra-hemispheric EEG coherences of the AD patients having lower values in the alpha (9.5-10.5 Hz) band than those of the control group. It suggests that under stimulated and non-stimulated conditions, AD patients had impaired inter- and intra-hemispheric functional connections, indicating failure of brain activation in alpha-related frequency.
Alzheimer Disease ; diagnosis ; physiopathology ; Case-Control Studies ; Cerebral Cortex ; physiopathology ; Electrodes ; Electroencephalography ; Female ; Humans ; Male ; Middle Aged

The Seoul Neuropsychological Screening Battery (SNSB) is one of the standardized neuropsychological test batteries widely used in Korea. However, it may be a bit too lengthy for patients with decreased attention span; and it does not provide the score of global cognitive function (GCF), which is useful for monitoring patients longitudinally. We sought to validate a dementia version of SNSB (SNSB-D) that was shorter than the original SNSB and contained only scorable tests with a GCF score of 300. We administered SNSB-D to patients with mild cognitive impairment (MCI) (n=43) and Alzheimer's disease (AD) (n=93), and normal controls (NC) (n=77). MCI and AD groups had GCF scores significantly different from NC group, and GCF scores were able to distinguish patients with Clinical Dementia Rating of 0.5 and 1. Test-retest reliability was high, with a correlation coefficient of 0.918 for AD, 0.999 for MCI, and 0.960 for NC. The GCF score significantly correlated with the Mini-Mental State Examination (MMSE). Through ROC-curve analysis, GCF scores were found to yield more accurate diagnoses than the MMSE. The SNSB-D is a valid, reliable tool for assessing the overall cognitive function, and can be used to monitor cognitive changes in patients with dementia.
Alzheimer Disease/diagnosis/physiopathology ; Cognition Disorders/*diagnosis/etiology/physiopathology ; Dementia/complications/*diagnosis/physiopathology ; Humans ; Korea ; *Neuropsychological Tests/standards ; ROC Curve ; Reproducibility of Results ; Severity of Illness Index

Alzheimer's disease (AD), the most common type of dementia, is becoming a major challenge for global health and social care. However, the current understanding of AD pathogenesis is limited, and no early diagnosis and disease-modifying therapy are currently available. During the past year, significant progress has been made in clinical research on the diagnosis, prevention, and treatment of AD. In this review, we summarize the latest achievements, including diagnostic biomarkers, polygenic hazard score, amyloid and tau PET imaging, clinical trials targeting amyloid-beta (Aβ), tau, and neurotransmitters, early intervention, and primary prevention and systemic intervention approaches, and provide novel perspectives for further efforts to understand and cure the disease.
Alzheimer Disease ; diagnosis ; physiopathology ; therapy ; Animals ; Biomarkers ; blood ; Biomedical Research ; methods ; Disease Progression ; Humans ; Magnetic Resonance Imaging

BACKGROUNDPrevious studies have shown that the functional brain activity in the resting state is impaired in Alzheimer's disease (AD) patients. However, most studies focused on the relationship between different brain areas, rather than the amplitude or strength of the regional brain activity. The purpose of this study was to explore the functional brain changes in AD patients by measuring the amplitude of the blood oxygenation level dependent (BOLD) functional MRI (fMRI) signals.

METHODSTwenty mild AD patients and twenty healthy elderly subjects participated in the fMRI scan. The amplitude of low frequency fluctuation (ALFF) was calculated using REST software.

RESULTSCompared with the healthy elderly subjects, the mild AD patients showed decreased ALFF in the right posterior cingulate cortex, right ventral medial prefrontal cortex, and in the bilateral dorsal medial prefrontal cortex. No brain region with increased ALFF was found in the AD group compared with the control group.

CONCLUSIONSThe reduced activity in the posterior cingulate cortex and medial prefrontal cortex observed in the present study suggest that the functional abnormalities of those areas are at an early stage of AD. The ALFF analysis may provide a useful tool in fMRI study of AD.

Aged ; Alzheimer Disease ; diagnosis ; physiopathology ; Case-Control Studies ; Female ; Gyrus Cinguli ; physiopathology ; Humans ; Magnetic Resonance Imaging ; methods ; Male ; Middle Aged ; Prefrontal Cortex ; physiopathology

OBJECTIVE: To analyze the relationship between olfactory bulb (OB) volume, depth of olfactory sulcus (OS) and olfactory function in patients with Alzheimer' disease (AD). METHOD: Fifty patients with AD patients and 50 healthy subjects were examined by olfactory function T&T testing, OB volume and depth of OS assessed with Magnetic resonance imaging (MRI). RESULT: T&T olfactory testing revealed that AD patients had higher scores than control group (1.50 ± 0.17, 2.80 ± 0.31, P < 0.05). Bilateral and average OB volumes were smaller in AD group [(29.78 ± 5.17) mm3, (30.14 ± 4.87)mm3, (30.05 ± 5.08) mm3] than in control group [(36.65 ± 4.08)mm3, (36.56 ± 4.12)mm3, (36.46 ± 4.11)mm3] (P < 0.01). OS depth study revealed no statistical difference between AD patients and control groups (P > 0.05). Olfactory discriminate threshold was negatively correlated with average olfactory bulb volumes (r = -0. 711, P < 0.05), and was not correlated with depth of OS (r = -0.127, P > 0.05) in AD patients. CONCLUSION The OB volume were lower in AD patients as compare to controls, the depth of OS has no significant changes in AD patients; The OB volume is correlated with olfactory function, the depth of OS is no correlated with olfactory function. Cognitive impairment degree in AD patients is accordance with the lower degree olfactory function. The olfactory loss may be the earlier period and objective diagnosis indicator for AD patients.
Alzheimer Disease ; complications ; physiopathology ; Case-Control Studies ; Humans ; Magnetic Resonance Imaging ; Olfaction Disorders ; complications ; diagnosis ; Olfactory Bulb ; anatomy & histology

Alzheimer's disease (AD) is an age-related, progressive neurodegenerative disorder that occurs gradually and results in memory, behavior, and personality changes. Abnormal sphingolipid metabolism was reported in AD previously. This study aimed to investigate whether sphK1 could exacerbate the accumulation of amyloid protein (Aβ) and sharpen the learning and memory ability of the animal model of AD using siRNA interference. An adenovirus vector expressing small interfering RNA (siRNA) against the sphK1 gene (sphK1-siRNA) was designed, and the effects of sphK1-siRNA on the APP/PS1 mouse four weeks after treatment with sphK1-siRNA hippocampal injection were examined. SphK1 protein expression was confirmed by using Western blotting and ceramide content coupled with S1P secretion was evaluated by enzyme-linked immunosorbent assay (ELISA). Aβ load was detected by immunohistochemical staining and ELISA. Morris water maze was adopted to test the learning and memory ability of the APP/PS1 mice. A significant difference in the expression of sphK1 protein and mRNA was observed between the siRNA group and the control group. Aβ load in transfected mice was accelerated in vivo, with significant aggravation of the learning and memory ability. The sphK1 gene modulation in the Aβ load and the learning and memory ability in the animal model of AD may be important for the treatment of AD.
Alzheimer Disease ; diagnosis ; physiopathology ; therapy ; Animals ; Disease Models, Animal ; Gene Silencing ; Genetic Therapy ; methods ; Learning Disorders ; diagnosis ; physiopathology ; therapy ; Mice ; Mice, Transgenic ; Microinjections ; Phosphotransferases (Alcohol Group Acceptor) ; genetics ; RNA, Small Interfering ; administration & dosage ; genetics ; therapeutic use ; Treatment Outcome

OBJECTIVETo compare the sex differences on brain stem auditory evoked potentials (BAEP) and P300 in the elderly patients with mild cognitive impairment (MCI) and the patients with Alzheimer's disease (AD).

METHODSThirty-eight elderly patients with MCI, 26 cases of AD and 20 health controls (HC) were examined with BAEP, P300 . Sex difference of the variables was compared inter-and intra-groups.

RESULTSSignificant sex differences of BAEP were found in the latency period wave III, V of left side in the MCI group (P <0.01), in the latency period wave IV, V of left side in HC group (P<0.01), and no such differences were found in AD group. The females had longer latency period in P300 measurement than males in MCI group (P <0.01), but there were no significant differences within AD or HC groups. The males showed significant differences in wave I, II in left side between the MCI and AD groups. The males also showed significant difference in wave I, III approximate, equals V in left side, wave IV in right side between AD and HC groups, and so did the females in wave I approximate, equals V in both sides. The males had significant difference in the left wave III, IV and right wave I, IV, V between MCI and HC groups, and so did the females in right side wave I, II, V. In P300, longer latency waves were found in AD group than in MCI group. Both sexes showed significant differences in the latency of Fz, Cz, Pz between AD and HC groups, but no significant differences were found in the latency of Fz, Cz, Pz in the females between the MCI and HC groups.

CONCLUSIONSex differences were found in the examination of both BAEP and P300 in MCI group, but not in AD group. The people of same sex have different expression of BAEP and P300 among MCI, AD and HC groups, suggesting the sex difference should be considered in the differential diagnosis.

Aged ; Aged, 80 and over ; Alzheimer Disease ; diagnosis ; physiopathology ; Cognition Disorders ; diagnosis ; physiopathology ; Diagnosis, Differential ; Event-Related Potentials, P300 ; Evoked Potentials, Auditory, Brain Stem ; Female ; Humans ; Male ; Middle Aged ; Sex Factors