The role of purinergic receptors in neural repair and regeneration after spinal cord injury.

Spinal cord injury is a serious injury of the central nervous system that results in neurological deficits. The pathophysiological mechanisms underlying spinal cord injury, as well as the mechanisms involved in neural repair and regeneration, are highly complex. Although there have been many studies on these mechanisms, there is no effective intervention for such injury. In spinal cord injury, neural repair and regeneration is an important part of improving neurological function after injury, although the low regenerative ability of nerve cells and the difficulty in axonal and myelin regeneration after spinal cord injury hamper functional recovery. Large amounts of ATP and its metabolites are released after spinal cord injury and participate in various aspects of functional regulation by acting on purinergic receptors which are widely expressed in the spinal cord. These processes mediate intracellular and extracellular signalling pathways to improve neural repair and regeneration after spinal cord injury. This article reviews research on the mechanistic roles of purinergic receptors in spinal cord injury, highlighting the potential role of purinergic receptors as interventional targets for neural repair and regeneration after spinal cord injury.

The relationship between a fish-rich diet and poststroke cognitive impairment: A cross-sectional study with a follow-up in China.

ABSTRACT: Whether a fish-rich diet is positively associated with cognitive function after stroke remains unclear; thus, the present study investigated the relationship between them.The present study was part of a prospective multicenter study, in which 920 individuals (609 males, mean age, 62.78 ±â€Š11.79 years) were included from November 2013 to December 2015. The cognitive function of the patients was evaluated, and the diagnosis of poststroke cognitive impairment (PSCI) was made during their stay in the hospital. A subgroup of 439 patients from a single center was followed up for 4 to 6 years and was reassessed for cognitive function.According to the diagnostic criteria, the PSCI prevalence was lower in the fish-rich diet group (P < .05). After adjusting for demographic and clinical variables by logistic regression, patients with a habit of consuming a fish-rich diet had a lower risk of developing PSCI than patients without a fish-rich diet (odds ratio [OR]: 0.74; 95% confidence interval [CI]: 0.46-0.95). When MMSE score was considered the cognitive function outcome variable, the long-term cognitive function of the fish-rich diet group was better (28 [26-30] vs 27 [25-29], P < .01), but the statistical results were not significant after correcting for the related confounding factors (ß: 0.13; 95% CI: -0.99-1.25; P = .82).There was a negative relationship between consuming a fish-rich diet and the prevalence of PSCI, and there was no statistically significant difference in the relationship of a fish-rich diet on long-term cognitive function after stroke, which requires further study.

Human urinary kallidinogenase in acute ischemic stroke: A single-arm, multicenter, phase IV study (RESK study).

AIMS: Human urinary kallidinogenase (HUK) has shown favorable efficacies in acute ischemic stroke (AIS) treatment. We sought confirmation of the safety and efficacy of HUK for AIS in a large population. METHODS: RESK study enrolled patients with AIS of anterior circulation to receive HUK infusion. The primary endpoint was the incidence of treatment-emergent adverse events (AEs). Secondary endpoints assessed neurological and functional improvements and stroke recurrent rate. RESULTS: Of 1206 eligible patients, 1202 patients received at least one dose of HUK infusion and 983 (81.5%) completed the study. The incidence of treatment-emergent AEs and serious AEs were 55.99% and 2.41%, respectively. Pre-specified AEs of special interest occurred in 21.71% of patients, but the majority were mild and unrelated to therapy. Hypertension, age, treatment time, and drug combination were identified to be associated with drug-related blood pressure reduction. Neurological and functional evaluations revealed favorable outcomes from baseline to post-treatment assessment. The cumulative recurrence rate of stroke was 2.50% during the 90-day assessment. CONCLUSION: HUK had an acceptable safety and tolerability profile in AIS patients. Besides, HUK demonstrated the neurological and functional improvements in AIS, further confirming its clinical efficacy in a real-world large population.

Neuromodulatory therapies for patients with prolonged disorders of consciousness.

BACKGROUND: Reviving patients with prolonged disorders of consciousness (DOCs) has always been focused and challenging in medical research. Owing to the limited effectiveness of available medicine, recent research has increasingly turned towards neuromodulatory therapies, involving the stimulation of neural circuits. We summarised the progression of research regarding neuromodulatory therapies in the field of DOCs, compared the differences among different studies, in an attempt to explore optimal stimulation patterns and parameters, and analyzed the major limitations of the relevant studies to facilitate future research. METHODS: We performed a search in the PubMed database, using the concepts of DOCs and neuromodulation. Inclusion criteria were: articles in English, published after 2002, and reporting clinical trials of neuromodulatory therapies in human patients with DOCs. RESULTS: Overall, 187 published articles met the search criteria, and 60 articles met the inclusion criteria. There are differences among these studies regarding the clinical efficacies of neurostimulation techniques for patients with DOCs, and large-sample studies are still lacking. CONCLUSIONS: Neuromodulatory techniques were used as trial therapies for DOCs wherein their curative effects were controversial. The difficulties in detecting residual consciousness, the confounding effect between the natural course of the disease and therapeutic effect, and the heterogeneity across patients are the major limitations. Large-sample, well-designed studies, and innovations for both treatment and assessment are anticipated in future research.

Exercise test for patients with new-onset paroxysmal kinesigenic dyskinesia.

The pathogenesis of primary paroxysmal kinesigenic dyskinesia (PKD) remains unclear, and channelopathy is a possibility. In a pilot study, we found that PKD patients had abnormal exercise test (ET) results. To investigate the ET performances in patients affected by PKD, and the role of the channelopathies in the pathogenesis of PKD, we compared the ET results of PKD patients, control subjects, and hypokalemic periodic paralysis (HoPP) patients, and we analyzed ET changes in 32 PKD patients before and after treatment. Forty-four PKD patients underwent genetic testing for the PRRT2, SCN4A, and CLCN1 genes. Sixteen of 59 (27%) patients had abnormal ET results in the PKD group, while 28 of 35 (80%) patients had abnormal ET results in the HoPP group. Compared with the control group, the PKD group showed a significant decrease in the compound muscle action potential (CMAP) amplitude and area after the long ET (LET), while the HoPP group showed not only greater decreases in the CMAP amplitude and area after the LET but also greater increases in the CMAP amplitude and area immediately after the LET. The ET parameters before and after treatment were not significantly different. Nine of 44 PKD patients carried PRRT2 mutations, but the gene abnormalities were unrelated to any ET parameter. The PKD group demonstrated an abnormal LET result by electromyography (EMG), and this abnormality did not seem to correlate with the PRRT2 variant or sodium channel blocker therapy.

Novel compound heterozygous of PARKIN causes early-onset Parkinson's disease.

Genetics has an essential role in the development of early-onset Parkinson's disease (EOPD). Consequently, genetic screening is of great significance for the diagnosis and treatment of EOPD. In this study, we reported two EOPD with compound heterozygous in PARKIN detected by whole-exome sequencing (WES) and ligation-dependent probe amplification (MLPA). Two unrelated EOPD patients and their parents were enrolled in this study. Genetic analysis was performed through WES and verified by direct Sanger sequencing. In addition, MLPA was used to detect exon dosage. Detailed clinical manifestations and several scale assessments were collected for genotype and phenotype analysis. Compound heterozygous mutations in PARKIN were identified in both patients. c.735-1G > A and Ex2del were detected in Case A, while G284R (c.850 G > C) and Ex2del were found in Case B. These variants were confirmed to originate from their normal parents. The c.735-1G > A is a novel PARKIN variant, which was predicted to result from disappearing of the acceptor splice site by NetGene2. The G284R is a previously reported pathological mutation and the Ex2del is a hot variant of PARKIN found in the Asian population. The phenotypes of both patients are quite different, the main manifestation of case A is rigidity onset, while the case B starts with tremor and foot dystonia. In the present study, we reported a novel compound heterozygous form of PARKIN consisting of splice variant c. 735-1G > A and Ex2del. Moreover, we also found that tiny differences in genotypes of PARKIN may lead to obvious clinical phenotypic differences.

Gab1 mediates PDGF signaling and is essential to oligodendrocyte differentiation and CNS myelination.

Oligodendrocytes (OLs) myelinate axons and provide electrical insulation and trophic support for neurons in the central nervous system (CNS). Platelet-derived growth factor (PDGF) is critical for steady-state number and differentiation of oligodendrocyte precursor cells (OPCs), but its downstream targets are unclear. Here, we show for the first time that Gab1, an adaptor protein of receptor tyrosine kinase, is specifically expressed in OL lineage cells and is an essential effector of PDGF signaling in OPCs in mice. Gab1 is downregulated by PDGF stimulation and upregulated during OPC differentiation. Conditional deletions of Gab1 in OLs cause CNS hypomyelination by affecting OPC differentiation. Moreover, Gab1 binds to downstream GSK3ß and regulated its activity, and thereby affects the nuclear accumulation of ß-catenin and the expression of a number of transcription factors critical to myelination. Our work uncovers a novel downstream target of PDGF signaling, which is essential to OPC differentiation and CNS myelination.

A Grading Scale for Pial Collaterals in Middle Cerebral Artery Total Occlusion Based on Time-of-flight MR Angiography Source Images.

PURPOSE: To verify whether a new grading based on time-of-flight magnetic resonance angiography source images (TOF-MRAsi) can reflect the abundance of pial collaterals, in patients with total occlusion of M1 segment of middle cerebral artery in the chronic stage. METHODS: In this single-center retrospective study, consecutive patients with total occlusion of M1 segment of middle cerebral artery, with both magnetic resonances angiography and digital subtraction angiography image were included. Time-of-flight magnetic resonance angiography source images were evaluated in a blinded fashion for pial collaterals (PCs) that were graded on a four-point scale. Good and poor PCs were defined as TOF-MRAsis grade <2 and ≥2, respectively. Receiver operating characteristic curve analysis was done to calculate the area under curve, sensitivity, and specificity. RESULTS: A total of 26 patients were included. The inter-reader agreement for time TOF-MRAsi and digital subtraction angiography images were 0.930 and 0.843, respectively. Compared with digital subtraction angiography grading, the area under curve of pial collateral grading based on TOF-MRAsi was 0.830 (0.636-1.000; P = 0.006). The sensitivity and specificity were 0.700 and 0.933, respectively. The modified Rankin Scale at follow-up was lower in patients with good PCs than in those with poor PCs (0[0, 1] vs. 1[1, 3], P = 0.055), although statistical significance was not reached. CONCLUSION: The grading scale based on TOF-MRAsi could be a new empirical approach for pial collateral evaluation. The clinical use of the proposed approach for identifying patients with total occlusion of middle cerebral artery with a high risk of poor outcome requires evaluation in further studies.

Down-regulated expression of microRNA-338-5p contributes to neuropathology in Alzheimer's disease.

Alzheimer's disease (AD) is a leading cause of dementia. However, the mechanisms responsible for development of AD, especially for the sporadic variant, are still not clear. In our previous study, we discovered that a small noncoding RNA (miR-188-3p) targeting ß-site amyloid precursor protein cleaving enzyme (BACE)-1, a key enzyme responsible for Aß formation, plays an important role in the development of neuropathology in AD. In the present study, we identified that miR-338-5p, a new miRNA that also targets BACE1, contributes to AD neuropathology. We observed that expression of miR-338-5p was significantly down-regulated in the hippocampus of patients with AD and 5XFAD transgenic (TG) mice, an animal model of AD. Overexpression of miR-338-5p in the hippocampus of TG mice reduced BACE1 expression, Aß formation, and neuroinflammation. Overexpression of miR-338-5p functionally prevented impairments in long-term synaptic plasticity, learning ability, and memory retention in TG mice. In addition, we provide evidence that down-regulated expression of miR-338-5p in AD is regulated through the NF-κB signaling pathway. Our results suggest that down-regulated expression of miR-338-5p plays an important role in the development of AD.-Qian, Q., Zhang, J., He, F.-P., Bao, W.-X., Zheng, T.-T., Zhou, D.-M., Pan, H.-Y., Zhang, H., Zhang, X.-Q., He, X., Sun, B.-G., Luo, B.-Y., Chen, C., Peng, G.-P. Down-regulated expression of microRNA-338-5p contributes to neuropathology in Alzheimer's disease.

Intensive Versus Moderate Statin Therapy Discontinuation in Patients With Acute Ischemic Stroke or Transient Ischemic Attack.

PURPOSE: The differences of discontinuation risk between intensive and mild-to-moderate statin therapy in patients with acute ischemic stroke is not clear. This study aimed to clarify whether intensive statin therapy resulted in a significant increase in discontinuation early after discharge. METHODS: This multicenter registry study enrolled consecutive hospitalized patients with ischemic stroke or transient ischemic attack. All the patients were prescribed statin therapy at discharge. Intensity of statin therapy was defined according to the 2013 American College of Cardiology/American Heart Association guideline on the treatment of blood cholesterol. A logistic regression model was used to analyze the association between statin therapy intensity and discontinuation. FINDINGS: This study included 505 patients, of whom 64 and 441 received intensive and moderate statin therapy, respectively (mean follow-up, approximately 6 months). The rates of discontinuation of intensive and moderate statin therapy were 31.3% and 10.7% (P < 0.001), respectively. Variables with significant differences between the intensive and moderate statin therapy groups were included in the adjusted logistic regression model. Intensive statin therapy significantly increased discontinuation risk by 273.0% (odds ratio = 3.730; 95% CI, 2.013-6.911; P < .001) compared with moderate statin therapy. The result was consistent in most subgroups, except for patients with National Institutes of Health Stroke Scale scores ≥4. IMPLICATIONS: In stroke secondary prevention, intensive statin therapy may significantly increase the risk of early discontinuation compared with moderate statin therapy. Future clinical trials that involve a comparison between intensive and moderate statin therapy for stroke secondary prevention should address the differences in discontinuation between these 2 groups.

Effect of acoustic stimuli in patients with disorders of consciousness: a quantitative electroencephalography study.

Auditory stimuli are proposed as beneficial neurorehabilitation methods in patients with disorders of consciousness. However, precise and accurate quantitative indices to estimate their potential effect remain scarce. Fourteen patients were recruited from the Neuro-Rehabilitation Unit of Hangzhou Hospital of Zhejiang Armed Police Corps of China. Altogether, there were seven cases of unresponsive wakefulness syndrome (five males and two females, aged 45.7 ± 16.8 years) and seven cases of minimally conscious state (six males and one female, aged 42.3 ± 20.8 years). Simultaneously, fourteen healthy controls (10 males and 4 females, aged 51.7 ± 9.7 years) also participated in this case-control experiment. Brain response to music, subjects' own name, and noise was monitored by quantitative electroencephalography (QEEG) in the resting state and with acoustic stimulation. Predictive QEEG values in various brain regions were investigated. Our results show that cerebral activation was high in subjects stimulated by their own name, especially in the temporal lobe in patients with disorders of consciousness, and the frontal lobe in the control group. Further, during resting and stimulation, QEEG index (δ + θ/α + ß ratio) negatively correlated with the Coma Recovery Scale-Revised score in traumatic disorders of consciousness patients. Hence, we speculate that a subject's own name might be an effective awakening therapy for patients with disorders of consciousness. Moreover, QEEG index in specific stimulation states may be used as a prognostic indicator for disorders of consciousness patients (sensitivity, 75%; specificity, 50%). This clinical study has been registered at ClinicalTrials.gov (identifier: NCT03385291).

Dorsal CA1 interneurons contribute to acute stress-induced spatial memory deficits.

Exposure to severely stressful experiences disrupts the activity of neuronal circuits and impairs declarative memory. GABAergic interneurons coordinate neuronal network activity, but their involvement in stress-evoked memory loss remains to be elucidated. Here, we provide evidence that interneurons in area CA1 of the dorsal hippocampus partially modulate acute stress-induced memory deficits. In adult male mice, both acute forced swim stress and restraint stress impaired hippocampus-dependent spatial memory and increased the density of c-fos-positive interneurons in the dorsal CA1. Selective activation of dorsal CA1 interneurons by chemogenetics disrupted memory performance in the spatial object recognition task. In comparison, anxiety-related behavior, spatial working memory and novel object recognition memory remained intact when dorsal CA1 interneurons were overactivated. Moreover, chemogenetic activation of dorsal CA1 interneurons suppressed the activity of adjacent pyramidal neurons, whereas a single exposure to forced swim stress but not restraint stress increased the activity of CA1 pyramidal neurons. However, chemogenetic inhibition of dorsal CA1 interneurons led to spatial memory impairments and failed to attenuate acute stress-induced memory loss. These findings suggest that acute stress may overactivate interneurons in the dorsal CA1, which reduces the activity of pyramidal neurons and in turn disrupts long-term memory.

Age and composite end-point events in medium follow-up of patients with carotid artery total occlusion using drug therapy.

BACKGROUND AND AIMS: The outcome of carotid artery total occlusion (CATO) is unclear. The aim of this study is to report the medium incidence of composite end-point events and risk factors (especially age), in patients with CATO, treated medically. METHODS: This was a single center retrospective study. Composite end-point events included death, ischemic stroke, transient ischemic attack, hemorrhagic stroke, myocardial infarction, or angina. Logistic regression analysis was used to analyze risk factors of composite end-point events. RESULTS: A total of 94 patients with CATO were included in the study. The mean follow-up duration was 30 ± 16 months. There were 16 cases who experienced composite end-point events (17.0%); among them, there were 15 cases of death (16.0%), 8 cases of ischemic stroke (7 cases of fatal stroke and 1 case of non-fatal stroke) (8.5%), and 1 case of angina pectoris (1%) (the patient later developed ischemic stroke). With increased age, the incidence of composite end-point events was significantly increased (p = 0.002). Multivariate logistic regression analysis showed that only age was a risk factor (OR = 3.051 (1.351-6.890), p = 0.007). CONCLUSIONS: The incidence of composite end-point events in patients with CATO was as high as 17.0% at approximately 3 years after drug therapy alone. For every 10 years of age increase, the risk increase of composite end-point events doubles.

Correlations between diffusion tensor imaging and levels of consciousness in patients with traumatic brain injury: a systematic review and meta-analysis.

Traumatic brain injury (TBI) often leads to impaired consciousness. Recent diffusion tensor imaging studies associated consciousness with imaging metrics including fractional anisotropy (FA) and apparent diffusion coefficient (ADC). We evaluated their correlations and determined the best index in candidate regions. Six databases were searched, including PubMed and Embase, and 16 studies with 701 participants were included. Data from region-of-interest and whole-brain analysis methods were meta-analysed separately. The FA-consciousness correlation was marginal in the whole-brain white matter (r = 0.63, 95% CI [0.47, 0.79], p = 0.000) and the corpus callosum (CC) (r = 0.60, 95% CI [0.48, 0.71], p = 0.000), and moderate in the internal capsule (r = 0.48, 95% CI [0.24, 0.72], p = 0.000). Correlations with ADC trended negative and lacked significance. Further subgroup analysis revealed that consciousness levels correlated strongly with FA in the CC body (r = 0.66, 95% CI [0.43, 0.89]), moderately in the splenium (r = 0.58, 95% CI [0.38, 0.78]), but insignificantly in the genu. In conclusion, FA correlates better with consciousness levels than ADC in TBI. The degree of correlation varies among brain regions. The CC (especially its splenium and body) is a reliable candidate region to quantitatively reflect consciousness levels.

Correlation of Stress Hyperglycemia after Ischemic Stroke with Early Vascular Cognitive Impairment.

Objective To investigate the influence and forecast value of stress hyperglycemia on the early vascular cognitive impairment (VCI) in stroke patients.Methods Totally 422 patients with acute non-diabetic stroke were divided into three groups according to the fasting plasma glucose level:the euglycemia group (<6.1 mmol/L),the mild stress hyperglycemia group (6.1-7.0 mmol/L),and the severe stress hyperglycemia group (≥7.0 mmol/L).Mini-mental state examination,Alzheimer's disease rating scale cognitive subscale,and clinical dementia rating scale were used to evaluate early cognition in post-stroke patients,and patients were divided into three groups accordingly:normal cognitive function group,mild VCI group,and vascular dementia group.Correlation analysis was carried out on the level of stress hyperglycemia and the degree of VCI.Results Of these 422 patients,stress hyperglycemia was identified in 62 cases (14.7%).The risk of stress hyperglycemia was higher in patients with a high degree of education [(8.39±3.85)years vs.(6.62±4.39)years,P=0.037)] or a history of cardiovascular disease (45.2% vs.18.3%,P=0.001).VCI was detected in 270 patients (64.0%).Age,sex,smoking,National Institute of Health Stroke Scale score,Hamilton Depression Rating Scale score,stress hyperglycemia,and history of cardiovascular disease were related with early VCI after non-diabetic ischemic stroke (P<0.05).Multivariate Logistic regression analysis showed that stress hyperglycemia was an independent risk factor for VCI in patients with non-diabetic ischemic stroke (OR=3.086,95% CI=1.065-8.929).The risks of cognitive impairment in the mild stress hyperglycemia group and the severe stress hyperglycemia group were higher than that of the euglycemia group,while it was also higher in the severe stress hyperglycemia group than in the mild stress hyperglycemia group (61.11% vs.75.00% vs.90.91%).Stress hyperglycemia was positively correlated with the high risk of early cognitive impairment in stroke patients (rs=0.185,P=0.007).Conclusion There is a significant correlation between stress hyperglycemia and early VCI after ischemic stroke.

[Carotid artery dissection with Horner syndrome as main manifestation: a case report].

A 44-year old male patient was admitted to the First Affiliated Hospital, Zhejiang University School of Medicine with left ptosis and pain on the left head and neck for 20 days.Brain MRI showed subacute cerebral infarction on left parietal lobe and intramural hematoma on left internal carotid artery. CT angiography showed stenosis line on the C1 segment of left internal carotid artery. Digital subtraction angiography showed dissection on the C1 segment of left internal carotid artery.The condition of patients was improved after anticoagulant therapy.

Impact of libido at 2 weeks after stroke on risk of stroke recurrence at 1-year in a chinese stroke cohort study.

BACKGROUND: There were few studies on the relation between changes in libido and incidence of stroke recurrence. The aim of this study was to investigate the relationship between libido decrease at 2 weeks after stroke and recurrent stroke at 1-year. METHODS: It is a multi-centered, prospective cohort study. The 14 th item of the Hamilton Depression Rating Scale-17 was used to evaluate changes of libido in poststroke patients at 2 weeks. Stroke recurrence was defined as an aggravation of former neurological functional deficit, new local or overall symptoms, or stroke diagnosed at re-admission. RESULTS: Among 2341 enrolled patients, 1757 patients had completed follow-up data, 533 (30.34%) patients had decreased libido at 2 weeks, and 166 (9.45%) patients had recurrent stroke at 1-year. Multivariate logistic regression analysis showed that, compared with patients with normal libido, the odds ratio (OR) of recurrent stroke in patients with decreased libido was reduced by 41% (OR = 0.59, 95% confidence interval [CI]: 0.40-0.87). The correlation was more prominent among male patients (OR = 0.52, 95% CI: 0.31-0.85) and patients of ≥60 years of age (OR = 0.57, 95% CI: 0.35-0.93). CONCLUSIONS: One out of three stroke patients in mainland China has decreased libido at 2 weeks after stroke. Decreased libido is a protective factor for stroke recurrence at 1-year, which is more prominent among older male patients.

Inhibition of receptor-interacting protein 3 upregulation and nuclear translocation involved in Necrostatin-1 protection against hippocampal neuronal programmed necrosis induced by ischemia/reperfusion injury.

Receptor-interacting protein 3 (RIP3) is a key molecular switch in tumor necrosis factor-induced necroptosis requiring the formation of an RIP3-RIP1 complex. We have recently shown that hippocampal cornu ammonis 1 (CA1) neuronal death induced by 20-min global cerebral ischemia/reperfusion (I/R) injury is a form of programmed necrosis. However, the mechanism behind this process is still unclear and was studied here. Global cerebral ischemia was induced by the four-vessel occlusion method and Necrostatin-1 (Nec-1), a specific inhibitor of necroptosis, was administered by intracerebroventricular injection 1h before ischemia. Normally, in the hippocampal CA1 neurons, RIP1 and RIP3 are located in the cytoplasm. However, after I/R injury, RIP3 was upregulated and translocated to the nucleus while RIP1 was not affected. Nec-1 pretreatment prevented hippocampal CA1 neuronal death and I/R induced changes in RIP3. Decreased level of NAD+ in hippocampus and the release of cathepsin-B from lysosomes after I/R injury were also inhibited by Nec-1. Our data demonstrate that Nec-1 inhibits neuronal death by preventing RIP3 upregulation and nuclear translocation, as well as NAD+ depletion and cathepsin-B release. The nuclear translocation of RIP3 has not been reported previously, so this may be an important role for RIP3 during ischemic injury.

Correlation of hippocampal volume and cognitive performances in patients with either mild cognitive impairment or Alzheimer's disease.

OBJECTIVE: To evaluate hippocampal volume changes and neuropsychological performances in patients with either amnestic mild cognitive impairment (aMCI) or Alzheimer's disease (AD). METHODS: Thirty-eight AD dementia, 22 aMCI patients, and 20 healthy controls were enrolled. Bilateral hippocampal volume was measured concurrently with mini-mental state examination (MMSE), auditory verbal learning test (AVLT), Boston naming test (BNT), and activities of daily living (ADL) test. Baseline and two additional follow-up examinations were conducted. RESULTS: Baseline hippocampal volumes were significantly smaller in AD group than that in aMCI and control groups. MMSE, AVLT, ADL, and BNT scores for the AD group were significantly different from that of both aMCI and control groups. Baseline hippocampal volumes were positively correlated with MMSE and AVLT scores in AD and aMCI patients. At follow-up, left hippocampal volume loss was positively correlated with decreased MMSE and AVLT scores both in AD and aMCI groups, while right hippocampal volume loss was positively associated with decreased AVLT performance only in AD group. Increased ADL and decreased BNT scores were positively associated with left hippocampal volume reduction only in the AD group. CONCLUSIONS: Current findings provide evidence of a close relationship between hippocampal volume and cognitive performances in patients with AD and aMCI, both at baseline and over follow-up.