BACKGROUNDPrevious studies have shown that brain functional activity in the resting state is impaired in Alzheimer's disease (AD) patients. However, alterations in intrinsic brain activity patterns in mild cognitive impairment (MCI) patients are poorly understood. This study aimed to explore the differences in regional intrinsic activities throughout the whole brain between aMCI patients and controls.

METHODSIn the present study, resting-state functional magnetic resonance imaging (fMRI) was performed on 18 amnestic MCI (aMCI) patients, 18 mild AD patients and 20 healthy elderly subjects. And amplitude of low-frequency fluctuation (ALFF) method was used.

RESULTSCompared with healthy elderly subjects, aMCI patients showed decreased ALFF in the right hippocampus and parahippocampal cortex, left lateral temporal cortex, and right ventral medial prefrontal cortex (vMPFC) and increased ALFF in the left temporal-parietal junction (TPJ) and inferior parietal lobule (IPL). Mild AD patients showed decreased ALFF in the left TPJ, posterior IPL (pIPL), and dorsolateral prefrontal cortex compared with aMCI patients. Mild AD patients also had decreased ALFF in the right posterior cingulate cortex, right vMPFC and bilateral dorsal MPFC (dMPFC) compared with healthy elderly subjects.

CONCLUSIONSDecreased intrinsic activities in brain regions closely related to episodic memory were found in aMCI and AD patients. Increased TPJ and IPL activity may indicate compensatory mechanisms for loss of memory function in aMCI patients. These findings suggest that the fMRI based on ALFF analysis may provide a useful tool in the study of aMCI patients.

Aged ; Alzheimer Disease ; physiopathology ; Amnesia ; physiopathology ; Brain ; physiopathology ; Cognitive Dysfunction ; physiopathology ; Female ; Humans ; Magnetic Resonance Imaging ; Male

We studied the mechanism of electroencephalography (EEG) in the elderly with mild cognitive impairment (MCI) by analyzing the Lempel-Ziv complexity (LZC) of EEG during a cognitive task. We recorded the EEG simultaneously when they were asked to judge whether the color of two graphics was matched or not. The results showed that the LZC of EEG in the MCI group was significantly higher than those in the normal control group early in the period of cognitive activities (P < 0.05). The LZC in MCI patients decreased gradually over time, while results of the normal group kept unchanged. There was no significant difference in LZC between two types of tasks. The two groups showed similar regularity in spatial distribution.
Aged ; Algorithms ; Cognitive Dysfunction ; diagnosis ; physiopathology ; Electroencephalography ; methods ; Female ; Humans ; Male ; Signal Processing, Computer-Assisted

BACKGROUNDSuccessful aging (SA) and mild cognitive impairment (MCI) are heterogeneous groups of aging. To explore the heterogeneity, the functional connectivity was studied in these populations.

METHODSThe present study utilized functional connectivity magnetic resonance imaging (fcMRI) to investigate default mode network (DMN) in 8 healthy subjects of SA, 8 subjects of usual aging (UA), and 8 MCI patients during verbal fluency tests (VFTs). Functional connectivity (based seeds) of different groups was analyzed by using statistical test.

RESULTSCompared with SA and UA groups, MCI subjects exhibited decreased functional connectivity in the DMN regions, including the inferior parietal lobule and left angular gyrus (t = 3.53, P < 0.001). Compared with UA and MCI groups, the SA elderly exhibited increased functional connectivity in the precuneus (t = 3.53, P < 0.001).

CONCLUSIONSThese findings suggested that abnormalities of functional connectivity in DMN might be related with semantic memory impairment in aging. Left angular gyrus and precuneus might be the potential imaging-based biomarker for distinguishing heterogeneous process of elderly.

Aged ; Aged, 80 and over ; Aging ; physiology ; Brain ; physiopathology ; Cognitive Dysfunction ; physiopathology ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Neuropsychological Tests

Objective: To investigate the association between people who were under lack of care in childhood and the development of cognitive impairment in their middle-aged and elderly life spans. Methods: Based on the baseline survey data of the third phase of "Guangzhou Biobank Cohort study" conducted from January 2007 to January 2008, 9 223 residents aged ≥50 years with records on Mini Mental State Examination (MMSE) were included in a retrospective survey on received childhood care of their early lives. Questions would include: feelings of care and support from their close relatives during childhood, the status of separation from their mothers for ≥1 year, and the current status of their parents. Linear regression, unconditional and multinomial logistic regression models were used to analyze the associations between the received childhood care and cognitive function (i.e., MMSE scores and cognitive impairment) in middle and old age, of this population under study. Results: After adjusting for age, gender, education, place of residence, marital status, physical activity, smoking, drinking, occupation, personal income, childhood socioeconomic position and depressive symptoms etc., factors as feeling lack of concern and support from close relatives (LC), status of separation from the mother for ≥1 year (SM), and the current status of their parents etc., were all negatively associated with the MMSE score when in middle and old age, with partial regression coefficient β (95%CI) as -0.44 (-0.65- -0.23), -0.26 (-0.38- -0.14) and -0.61 (-0.96- -0.27), respectively. The presence of LC, SM or PD were associated with the increased risks of cognitive impairment, and the adjusted odds ratio OR (95%CI) appeared as 1.43 (1.15-1.78), 1.26 (1.08-1.47) and 1.64 (1.16-2.31) respectively in all the participants, but 1.27 (1.01-1.62), 1.29 (1.09-1.55) and 1.75 (1.19-2.55) respectively, in those with education level of primary school or below. In those with secondary school education or above, only the presence of item A was associated with an increased risk of cognitive impairment (OR=2.26, 95%CI: 1.41-3.50). Conclusion: We noticed that 'lack of care' in childhood was associated with cognitive impairment during middle and old age, mainly in those population with lower education.
Aged ; Cognition/physiology* ; Cognition Disorders/physiopathology* ; Cognitive Dysfunction/physiopathology* ; Humans ; Linear Models ; Middle Aged ; Odds Ratio ; Retrospective Studies ; Surveys and Questionnaires

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

Chronic stress is generally accepted as the main risk factor in the development of cognitive decline; however, the underlying mechanisms remain unclear. Previous data have demonstrated that the levels of homocysteine (Hcy) are significantly elevated in the plasma of stressed animals, which suggests that Hcy is associated with stress and cognitive decline. To test this hypothesis, we analyzed the cognitive function, plasma concentrations of Hcy, and brain-derived neurotropic factor (BDNF) levels in rats undergoing chronic unpredicted mild stress (CUMS). The results showed that decreased cognitive behavioral performance and decreased BDNF transcription and protein expression were correlated with hyperhomocysteinemia (HHcy) levels in stressed rats. Diet-induced HHcy mimicked the cognitive decline and BDNF downregulation in the same manner as CUMS, while Hcy reduction (by means of vitamin B complex supplements) alleviated the cognitive deficits and BDNF reduction in CUMS rats. Furthermore, we also found that both stress and HHcy disturbed the DNA methylation process in the brain and induced DNA hypermethylation in the BDNF promoter. In contrast, control of Hcy blocked BDNF promoter methylation and upregulated BDNF levels in the brain. These results imply the possibility of a causal role of Hcy in stress-induced cognitive decline. We also used ten-eleven translocation (TET1), an enzyme that induces DNA demethylation, to verify the involvement of Hcy and DNA methylation in the regulation of BDNF expression and the development of stress-related cognitive decline. The data showed that TET1-expressing viral injection into the hippocampus inhibited BDNF promoter methylation and significantly mitigated the cognitive decline in HHcy rats. Taken together, novel evidence from the present study suggests that Hcy is likely involved in chronic stress-induced BDNF reduction and related cognitive deficits. In addition, the negative side-effects of HHcy may be associated with Hcy-induced DNA hypermethylation in the BDNF promoter. The results also suggest the possibility of Hcy as a target for therapy and the potential value of vitamin B intake in preventing stress-induced cognitive decline.
Animals ; Brain-Derived Neurotrophic Factor/metabolism* ; Cognitive Dysfunction/complications* ; DNA Methylation ; Homocysteine/metabolism* ; Hyperhomocysteinemia/metabolism* ; Rats ; Stress, Psychological/physiopathology*

BACKGROUNDCognitive impairment is a severe complication caused by obstructive sleep apnea (OSA). The mechanisms of causation are still unclear. The Wnt/β-catenin signaling pathway is involved in cognition, and abnormalities in it are implicated in neurological disorders. Here, we explored the Wnt/β-catenin signaling pathway abnormalities caused by chronic intermittent hypoxia (CIH), the most characteristic pathophysiological component of OSA.

METHODSWe divided 32 4-week-old male C57/BL mice into four groups of eight each: a CIH + normal saline (NS) group, CIH + LiCl group, sham CIH + NS group, and a sham CIH + LiCl group. The spatial learning performance of each group was assessed by using the Morris water maze (MWM). Protein expressions of glycogen synthase kinase-3β (GSK-3β) and β-catenin in the hippocampus were examined using the Western blotting test. EdU labeling and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling staining methods were used, respectively, to determine the proliferation and apoptosis of neurons in the hippocampal dentate gyrus region.

RESULTSMice exposed to CIH showed impaired spatial learning performance in the MWM, including increased mean escape latencies to reach the target platform, decreased mean times passing through the target platform and mean duration in the target quadrant. The GSK-3β activity increased, and expression of β-catenin decreased significantly in the hippocampus of the CIH-exposed mice. Besides, CIH significantly increased hippocampal neuronal apoptosis, with an elevated apoptosis index. Meanwhile, LiCl decreased the activity of GSK-3β and increased the expression of β-catenin and partially reversed the spatial memory deficits in MWM and the apoptosis caused by CIH.

CONCLUSIONSWnt/β-catenin signaling pathway abnormalities possibly play an important role in the development of cognitive deficits among mice exposed to CIH and that LiCl might attenuate CIH-induced cognitive impairment via Wnt/β-catenin signaling pathway.

Animals ; Chronic Disease ; Cognitive Dysfunction ; etiology ; physiopathology ; Glycogen Synthase Kinase 3 beta ; physiology ; Hypoxia ; complications ; physiopathology ; Male ; Mice ; Mice, Inbred C57BL ; Wnt Signaling Pathway ; physiology ; beta Catenin ; physiology

The purpose of this study was to explore the differences in interhemispheric functional connectivity in patients with Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI) based on a triple network model consisting of the default mode network (DMN), salience network (SN), and executive control network (ECN). The technique of voxel-mirrored homotopic connectivity (VMHC) analysis was applied to explore the aberrant connectivity of all patients. The results showed that: (1) the statistically significant connections of interhemispheric brain regions included DMN-related brain regions (i.e. precuneus, calcarine, fusiform, cuneus, lingual gyrus, temporal inferior gyrus, and hippocampus), SN-related brain regions (i.e. frontoinsular cortex), and ECN-related brain regions (i.e. frontal middle gyrus and frontal inferior); (2) the precuneus and frontal middle gyrus in the AD group exhibited lower VMHC values than those in the aMCI and healthy control (HC) groups, but no significant difference was observed between the aMCI and HC groups; and (3) significant correlations were found between peak VMHC results from the precuneus and Mini Mental State Examination (MMSE) and Montreal Cognitive Scale (MOCA) scores and their factor scores in the AD, aMCI, and AD plus aMCI groups, and between the results from the frontal middle gyrus and MOCA factor scores in the aMCI group. These findings indicated that impaired interhemispheric functional connectivity was observed in AD and could be a sensitive neuroimaging biomarker for AD. More specifically, the DMN was inhibited, while the SN and ECN were excited. VMHC results were correlated with MMSE and MOCA scores, highlighting that VMHC could be a sensitive neuroimaging biomarker for AD and the progression from aMCI to AD.
Aged ; Aged, 80 and over ; Alzheimer Disease/physiopathology* ; Brain/diagnostic imaging* ; Brain Mapping ; Cognitive Dysfunction/physiopathology* ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Memory ; Middle Aged ; Models, Neurological ; Nerve Net

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

OBJECTIVETo observe the efficacy on post-stroke mild cognitive impairment (MCI) treated with acupuncture at Jing-well points on the differentiated meridians and temple-three-needle therapy.

METHODSSeventy-three of stroke patients were randomized into an acupuncture group (37 cases) and a conventional treatment group (36 cases). Twenty healthy aged people in physical examination were collected as a control group. In the acupuncture group, on the basis of the conventional treatment of internal medication, the acupuncture at Jing-well points on the differentiated meridians and temple-three-needle therapy were applied. In the conventional treatment group, no any therapy was used except the conventional treatment of internal medication. In the control group, no any intervention was adopted. Neuroscan Nuamps electroencephalogram recording analysis system was used to determine the event-related potentials P300, and the amplitude and mini mental state examination (MMSE) score was observed before and after treatment in both groups.

RESULTSAfter treatment, in the acupuncture group, P300 latent stage was shortened, and the amplitude and the score of MMSE were increased (P < 0.05, P < 0.01). In the conventional treatment group, above indices were not changed obviously as compared with that before treatment (all P > 0.05). Compared with the conventional treatment group, the differences in P300 latent stage, amplitude and MMSE score were remarkable in the acupuncture group (P < 0.05, P < 0.01).

CONCLUSIONThe acupuncture at Jing-well points on the differentiated meridians and temple-three-needle therapy improves the cognitive function of the patients with MCI.

Acupuncture Points ; Acupuncture Therapy ; Adult ; Aged ; Aged, 80 and over ; Cognitive Dysfunction ; physiopathology ; therapy ; Event-Related Potentials, P300 ; Female ; Humans ; Male ; Meridians ; Middle Aged