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Background:Expression of neuronal thread protein (NTP), which is considered to be related to neuritic sprouting and neuronal death, may be elevated in brain tissue, cerebrospinal fluid, and even urine in patients with Alzheimer’s disease (AD).Objective:In this study, we analyzed the correlation between urine AD-associated NTP (AD7c-NTP) level, and amyloid-β (Aβ) deposition, and clinical symptoms in AD and mild cognitive impairment (MCI).Methods:Twenty-two patients with mild to moderate AD and 8 subjects with MCI were recruited. Aβ deposition was measured with [11C]-labeled Pittsburgh compound B (PiB)-positron emission tomography (PET) in all participants. Urine AD7c-NTP levels were measured using enzyme-linked immunosorbent assay. Mini-Mental State Examination (MMSE) and Neuropsychiatric Inventory (NPI) were used to evaluate cognitive function and behavioral psychological symptoms, respectively.Results:Fourteen (63.6%) of AD patients and 2 (25.0%) of MCI subjects were Aβ positive on PiB-PET. There was a significant difference in urine AD7c-NTP level between Aβ positive (2.27±2.22 ng/ml) and negative (0.55±0.60 ng/ml) subjects (p = 0.018). Using 1.46 ng/ml as a cut-off value, 68.8% of Aβ positive subjects showed elevated urine AD7c-NTP level, and 92.9% of Aβ negative subjects showed normal urine AD7c-NTP level. There were no relationships between urine AD7c-NTP level and MMSE and total NPI scores. However, AD7c-NTP level positively correlated with agitation score on NPI.Conclusions:Urine AD7c-NTP had high specificity and moderate sensitivity in predicting Aβ deposition among patients with cognitive impairment. Furthermore, urine AD7c-NTP level strongly correlated with the symptom of agitation.

aMCI and VCIND differ in cognitive function, memory strategy and sleep impairment; these characteristics are helpful to identify and distinguish patients with very early cognitive impairment. Our results also suggest that memory deficits are associated with sleep disturbance in aMCI and VCIND.

Hydroxysafflor yellow A (HSYA) has angiogenesisregulating and neuro-protective effects, but its effects on vascular dementia (VaD) are unknown. In this study, 30 adult Sprague-Dawley rats were randomly allocated to fi ve groups: normal, sham-operation, VaD alone (bilateral carotid artery occlusion), VaD plus saline (control), and VaD plus HSYA. One week after operation, the HSYA group received one daily tail-vein injection of 0.6 mg/100 g HSYA for two weeks. Five weeks after operation, the spatial memory of all fi ve groups was evaluated by the water maze task, and synaptic plasticity in the hippocampus was assessed by the long-term potentiation (LTP) method. Vascular endothelial growth factor (VEGF) and N-methyl-Daspartic acid receptor 1 (NR1) expression in the hippocampus was detected via Western blot. We found that, compared with the group with VaD alone, the group with HSYA had a reduced escape latency in the water maze (P <0.05), and the LTP at CA3-CA1 synapses in the hippocampus was enhanced (P <0.05). Western blot in the late-phase VaD group showed slight up-regulation of VEGF and downregulation of NR1 in the hippocampus, while HSYA signifi cantly up-regulated both VEGF and NR1. These results suggested that HSYA promotes angiogenesis and increases synaptic plasticity, thus improving spatial learning and memory in the rat model of VaD.

A growing body of evidence indicates that atherosclerosis is correlated with cerebral small vessel disease and contributes to cognitive decline. This study aimed to explore the characteristics and contributions of intracranial hemodynamics and carotid atherosclerosis to cognitive dysfunction in subjects with subcortical ischemic vascular dementia (SIVD). Notably, 44 patients with SIVD, 30 patients with Alzheimer’s disease (AD), and 30 healthy controls (HCs) were recruited from our longitudinal MRI study for AD and SIVD (ChiCTR1900027943). The cerebral mean flow velocity (MFV) and pulsatility index (PI) of both anterior and posterior circulations, artery plaque, and lumen diameter in carotid arteries were investigated using transcranial Doppler and carotid ultrasound, respectively. Their correlations with cognitive function were analyzed in patients with dementia. Decreased MFV and increased PI were found in patients with SIVD and AD. Patients with SIVD showed lower MFV and higher PI in the bilateral posterior cerebral arteries compared to patients with AD. Increases in lumen diameter, number of arteries with plaque, and total carotid plaque score were found in patients with SIVD. The Mini-Mental State Examination score was positively correlated with the MFV and negatively correlated with the PI of most major cerebral arteries, while it was negatively correlated with the lumen diameter of the common carotid artery, number of arteries with plaque, and total carotid plaque score in patients with dementia. There were also correlations between these parameters of some arteries and memory and executive function. Our results provide additional evidence suggesting that the pathological changes in macrovascular structure and function are correlated with cognitive impairment in dementia patients with SIVD and to a lesser extent AD.

Objective: Deficits in the semantic learning strategy were observed in subjects with amnestic mild cognitive impairment (aMCI) in our previous study. In the present study, we explored the contributions of executive function and brain structure changes to the decline in the semantic learning strategy in aMCI. Methods: A neuropsychological battery was used to test memory and executive function in 96 aMCI subjects and 90 age- and gender-matched healthy controls (HCs). The semantic clustering ratio on the verbal learning test was calculated to evaluate learning strategy. Medial temporal lobe atrophy (MTA) and white matter hyperintensities (WMH) were measured on MRI with the MTA and Fazekas visual rating scales, respectively. Results: Compared to HCs, aMCI subjects had poorer performance in terms of memory, executive function, and the semantic clustering ratio (P < .001). In aMCI subjects, no significant correlation between learning strategy and executive function was observed. aMCI subjects with obvious MTA demonstrated a lower semantic clustering ratio than those without MTA (P < .001). There was no significant difference in the learning strategies between subjects with high-grade WMH and subjects with low-grade WMH. Conclusion: aMCI subjects showed obvious impairment in the semantic learning strategy, which was attributable to MTA but independent of executive dysfunction and subcortical WMH. These findings need to be further validated in large cohorts with biomarkers identified using volumetric brain measurements. (JINS, 2019, 25, 706–717)

Cerebral hypoperfusion is an important factor in the pathogenesis of cerebrovascular diseases and neurodegenerative disorders. We investigated the effects of memantine and rosuvastatin on both neovascularization and synaptic function in a rat model of chronic cerebral hypoperfusion, which was established by the bilateral common carotid occlusion (2VO) method. We tested learning and memory ability, synaptic function, circulating endothelial progenitor cell (EPC) number, expression of neurotrophic factors, and markers of neovasculogenesis and cell proliferation after memantine and/or rosuvastatin treatment. Rats treated with memantine and/or rosuvastatin showed significant improvement in Morris water maze task and long-term potentiation (LTP) in the hippocampus, compared with untreated 2VO model rats. Circulating EPCs, expression of brain-derived neurotrophic factor, and vascular endothelial growth factor, markers of microvessel density were increased by each of the three interventions. Rosuvastatin also increased cell proliferation in the hippocampus. Combined treatment with memantine and rosuvastatin showed greater effect on enhancement of LTP and expression of neurotrophic factors than either single medication treatment alone. Both memantine and rosuvastatin improved learning and memory, enhanced neovascularization and synaptic function, and upregulated neurotrophic factors in a rat model of chronic cerebral hypoperfusion.