Alzheimer's disease with sleep insufficiency: a cross-sectional study on correlations among clinical characteristics, orexin, its receptors, and the blood-brain barrier.

Previous studies have shown that reduced sleep duration, sleep fragmentation, and decreased sleep quality in patients with Alzheimer's disease are related to dysfunction in orexin signaling. At the same time, blood-brain barrier disruption is considered an early biomarker of Alzheimer's disease. However, currently no report has examined how changes in orexin signaling relate to changes in the blood-brain barrier of patients who have Alzheimer's disease with sleep insufficiency. This cross-sectional study included 50 patients with Alzheimer's disease who received treatment in 2019 at Beijing Tiantan Hospital. Patients were divided into two groups: those with insufficient sleep (sleep duration ≤ 6 hours, n = 19, age 61.58 ± 8.54 years, 10 men) and those with normal sleep durations (sleep duration > 6 hours, n = 31, age 63.19 ± 10.09 years, 18 men). Demographic variables were collected to evaluate cognitive function, neuropsychiatric symptoms, and activities of daily living. The levels of orexin, its receptor proteins, and several blood-brain barrier factors were measured in cerebrospinal fluid. Sleep insufficiency was associated with impaired overall cognitive function that spanned multiple cognitive domains. Furthermore, levels of orexin and its receptors were upregulated in the cerebrospinal fluid, and the blood-brain barrier was destroyed. Both these events precipitated each other and accelerated the progression of Alzheimer's disease. These findings describe the clinical characteristics and potential mechanism underlying Alzheimer's disease accompanied by sleep deprivation. Inhibiting the upregulation of elements within the orexin system or preventing the breakdown of the blood-brain barrier could thus be targets for treating Alzheimer's disease.

Neuropsychological Features in Patients with General Paresis of the Insane at an Early Stage.

BACKGROUND This study aimed to explore the features of cognitive impairment in patients with neurosyphilis at the early stage of mild cognitive impairment (MCI). MATERIAL AND METHODS A total of 18 patients with asymptomatic neurosyphilis (ANS), 19 patients with neurosyphilis at the MCI stage (neurosyphilis-MCI), and 15 patients with neurosyphilis at the dementia stage (neurosyphilis-dementia) were enrolled. Cognitive function was evaluated using comprehensive rating scales. Tests of syphilis in blood and cerebrospinal fluid (CSF) were conducted, and white blood cell (WBC) counts and protein levels in CSF were measured. RESULTS Overall cognitive function and individual cognitive domains, including memory, language, visuospatial skill, and attention/executive function, were all significantly impaired in the neurosyphilis-MCI group compared with the ANS group, and were further impaired in the neurosyphilis-dementia group. Although there was no difference in serum rapid plasma regain (RPR) titer among the 3 groups, the number of patients with serum RPR titer ≥1: 32 in the neurosyphilis-MCI group was much higher than that in the ANS group. CSF RPR positive rate in the neurosyphilis-MCI group was significantly higher than that in the ANS group. The WBC count, protein level, and the rate of elevated protein level or increased WBC count in CSF did not differ among the 3 groups. CONCLUSIONS The feature of cognitive impairment of neurosyphilis-MCI patients displayed multiple-domain amnestic MCI. Perhaps there were extensive brain areas involved at the early stage, and a continuous neuroinflammatory process was through the different stages of neurosyphilis. Early diagnosis and treatment are very important for preventing the progression of general paresis of the insane.

Olfactory Dysfunction and Its Association With Neuropathologic Proteins in Cerebrospinal Fluid From Patients With Parkinson Disease.

Background and Purpose: Olfactory dysfunction (OD) is a common non-motor symptom of Parkinson disease (PD). However, the relationship between OD and neuropathologic proteins in cerebrospinal fluid (CSF) from PD patients remains unclear. Methods: 166 PD patients were included in the study. Overall olfactory function was assessed by summing up the scores of olfactory threshold, discrimination, and identification by a Sniffin' Sticks test, based on which, patients were divided into PD with OD (PD-OD) and PD with no OD (PD-NOD) groups. CSF samples were obtained from 76 PD patients. The levels of neuropathologic proteins, including α-Synuclein, Aß1-42, total tau (T-tau), and multiple forms of phosphorylated tau (P-tau) in CSF were measured by an enzyme-linked immunosorbent assay. Results: out of the 166 PD patients, 103 cases (62.0%) had OD. The scores of overall olfactory functions, and olfactory threshold, discrimination, and identification in the PD-OD group were all significantly lower than that in the PD-NOD group (P < 0.001). α-Synuclein level in CSF was significantly higher in the PD-OD group than the PD-NOD group (P < 0.05), and was significantly and negatively correlated with the scores of overall olfactory function, and olfactory discrimination and identification (P < 0.05). Aß1-42 level in CSF was higher in the PD-OD group than the PD-NOD group, and was significantly and negatively correlated with the olfactory identification score (P < 0.05). T-tau level in CSF was significantly lower in the PD-OD group than the PD-NOD group (P < 0.05), and was significantly and positively correlated with the olfactory discrimination score (P < 0.05). There was no significant difference in P-tau level in CSF between the PD-OD and PD-NOD groups and no correlation between OD score and P-tau level in CSF. Conclusions: PD-OD includes the impairments of olfactory threshold, discrimination, and identification, and is associated with the significant elevation of α-Synuclein and the decrease of the T-tau level in CSF.

Parkinson's Disease With Depression: The Correlations Between Neuroinflammatory Factors and Neurotransmitters in Cerebrospinal Fluid.

Background: To explore the changes of neuroinflammatory factors in cerebrospinal fluid (CSF) and their correlation with monoamine neurotransmitters in Parkinson's disease (PD) with depression (PD-D) patients. Methods: Neuroinflammatory factors and neurotransmitters in CSF were measured and compared between PD with no depression (PD-ND) and PD-D groups. The relationship between PD-D and neuroinflammatory factors was studied by binary logistic regression equation, and the related factors of PD-D were adjusted. The correlations of the levels of neuroinflammatory factors and neurotransmitters in PD-D group were analyzed. Results: The levels of tumor necrosis factor (TNF)-α in CSF from PD-D group were significantly higher and there were no significant differences in the levels of interleukin-1ß, prostaglandin (PG) E2, hydrogen peroxide (H2O2), and nitric oxide (NO). The 24-item Hamilton Depression Scale (HAMD-24) score was positively correlated with the level of TNF-α in CSF. Binary logistic regression showed that the OR of CSF TNF-α level was 1.035 (95% CI 1.002-1.069). The level of dopamine (DA) in CSF of PD-D group was significantly lower than that in PD-ND group. TNF-α level was negatively correlated with DA level in CSF from PD patients (r = -0.320, P = 0.003). Conclusions: Neuroinflammatory factors, especially TNF-α, may play an important role in PD-D. It may cause damage to DA neurons and lead to the depletion of DA, which is related to the occurrence and development of PD-D.

Correlations of apathy with clinical symptoms of Alzheimer's disease and olfactory dysfunctions: a cross-sectional study.

BACKGROUND: Apathy is one of the most common symptoms of Alzheimer's disease (AD), however, correlations of apathy with demographic variables, cognitive functions, neuropsychiatric symptoms, activity of daily living and olfactory functions in AD patients are still lacking comprehensive investigations. METHODS: This is a cross-sectional study. Total 124 typical AD patients were consecutively recruited from April 2014 to April 2017. In 124 AD patients, 47 cases (37.9%) were male and 77 cases were female; patients' age were 43-93 years with an average of 68 years. Patients were divided into AD with apathy (AD-A) and AD with no apathy (AD-NA) groups according to the score of Modified Apathy Evaluation Scale, then were evaluated cognitive functions, neuropsychiatric symptoms and activity of daily living, and tested olfactory functions. Above variables were compared between AD-A and AD-NA groups. Further correlation analyses and linear regression analysis were performed between apathy and above variables. RESULTS: Compared with AD-NA group, global cognitive level, verbal memory, verbal fluency and activity of daily living were significantly compromised in AD-A group (P < 0.002); depression and agitation were severely displayed in AD-A group (P < 0.002). Apathy was negatively correlated with global cognitive function, verbal memory, verbal fluency and activity of daily living (P < 0.05). There was no significant difference of olfactory functions between the two groups (P > 0.002), and correlations between apathy and olfactory threshold, olfactory identification and global olfactory function were significant (P < 0.05) but quite weak (|r| < 0.3). Further linear regression analysis showed that only verbal fluency and instrumental activities of daily living were independently associated with apathy. CONCLUSIONS: Independent correlations among apathy, verbal fluency and instrumental activities of daily living in AD patients might be related to the common brain area involved in their pathogeneses.

Clinical features and brain structural changes in magnetic resonance imaging in Alzheimer's disease patients with apathy.

BACKGROUND: Apathy is common in Alzheimer's disease (AD) patients. However, its relation with other clinical symptoms in AD and brain structural changes in magnetic resonance imaging is unclear. RESULTS: Compared with AD with no apathy group, cognitive function and activities of daily living were significantly impaired and neuropsychiatric symptoms were obviously presented in AD with apathy group (P<0.05). The frequency of Apolipoprotein E genotypes was not significantly different (P>0.05). Correlation analyses and multiple linear analyses revealed that thickness of left temporal pole and volume of posterior corpus callosum were significantly and negatively correlated with Modified Apathy Estimation Scale score in AD patients (P<0.05). CONCLUSIONS: Apathy with AD is positively correlated with cognitive impairment, neuropsychiatric symptoms and poor activities of daily living. Atrophy of left temporal pole and posterior corpus callosum presented by MRI is positively related with apathy of AD. METHODS: In this study, 137 AD patients were recruited and divided into AD with apathy group and AD with no apathy group according to Modified Apathy Estimation Scale score. We evaluated patients' cognitive function, neuropsychiatric symptoms and activities of daily living, detected the frequency of Apolipoprotein E genotypes and measured cortical thickness and volume by magnetic resonance imaging (MRI).

The Relationship Between Retinal Nerve Fiber Layer Thickness and Clinical Symptoms of Alzheimer's Disease.

Background/Aim: Retinal nerve fiber layer (RNFL) thickness (RT), which can reflect the status of the retinal optic nerve cells, may be affected in patients with Alzheimer's disease (AD). There are few studies on the correlation of RT of patients with AD (AD-RT) with clinical symptoms of various cognitive domains, neuropsychiatric symptoms, and activities of daily living (ADL). This study is to investigate the relationships between RT and the abovementioned clinical symptoms of AD. Methods: A total of 96 patients with AD were included in this study. RT was measured in these patients using optical coherence tomography (OCT). Demographic variables, RT, and clinical symptoms were compared between the normal and the abnormal AD-RT groups. Clinical symptoms, including cognitive symptoms, neuropsychiatric symptoms, and ADL, were evaluated using a series of rating scales. Results: The relationships between RT and cognitive symptoms scores were analyzed in patients with AD. Reduced RT was found in 54.4% of patients with AD. The average RT, RT of the superior 1/2 quadrant, and RT of the inferior 1/2 quadrant of both eyes were all significantly decreased in the abnormal AD-RT group (p < 0.001). Overall cognitive function and performance in multiple cognitive domains, including memory, language, attention, and executive function, were also significantly impaired in the abnormal AD-RT group (p < 0.05). For lower RT value, the global cognitive function and the performance in multiple cognitive domains were worse. ADL was significantly compromised in patients with AD having lower RT values (p < 0.05). Conclusions: Lower RT value appear to be correlated with cognitive impairment, and RT may be an indicator of cognitive decline in patients with AD. Further studies are required to confirm our findings.