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This practice guideline focuses on the cognitive assessment for mild cognitive impairment in the Guangdong-Hong Kong-Macao Greater Bay Area. To achieve the standardization and normalization of its clinical practice and generate individualized intervention, the National Core Cognitive Center of the Second Affiliated Hospital of Guangzhou Medical University, the Cognitive Disorders Branch of Chinese Geriatic Society, the Dementia Group of Neurology Branch of Guangdong Medical Association and specialists from Hong Kong and Macao developed guidelines based on China's actual conditions and efficiency, economic cost and accuracy. The article addresses the significance, background, and the process of the assessment and follow-up to realize the promotion and dissemination of cognitive assessment.

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Objective:To analyze the clinical characteristics of hereditary diffuse leukoencephalopathy with spheroids (HDLS).Methods:A retrospective analysis was performed. The clinical data of 2 patients with genetically conformed HDLS, admitted to our hospital in August 2020 and October 2021, were collected; and a literature search was conducted in domestic and foreign databases from January 2012 to January 2022 (enrolling a total of 48 patients with HDLS caused by colony-stimulating factor-1 receptor [ CSF1R] gene mutation). The population, clinical, imaging and gene mutation characteristics of these patients were summarized and analyzed. Results:(1) In these 50 patients, 20 were male and 30 were female, with onset age of (40.72±11.27) years; 40 patients (80.0%) had been misdiagnosed. (2) The most common first symptom and sign were progressive cognitive impairment (74.0%) and progressive dementia (80.0%). The patients in the middle and old aged group (≥40 years old, n=31) had significantly higher incidences of progressive cognitive impairment and Parkinson's-like symptom, and statistically lower incidence of muscle weakness as compared with those in the youth group (<40 years old, n=19, P<0.05). (3) The highest incidence of abnormal imaging findings was white matter lesions (100.0%), followed by cerebral atrophy (84.0%), ventricular enlargement (84.0%) and corpus callosum atrophy (60.0%). DWI examination was completed in 28 patients, and all patients showed persistent limitation of diffusion (100.0%). The most affected areas of white matter lesions were around the lateral ventricles, followed by the frontal-parietal occipital lobe, and corpus callosum. The incidence of abnormal signal of central semiovale in youth group was statistically higher than that in middle and old aged group ( P<0.05). (4) A total of 36 CSF1R gene mutations or possibly pathogenic mutations were identified in 50 patients, 21 of which were novel mutations reported for the first time. Of the 47 patients whose mutations were described in detail, 8 (17.0%) and 5 (10.6%) probands carried c. 2381T>C/p. I794T and c.2345G>A/p.R782H, respectively. Conclusions:The clinical manifestations of HDLS are diverse and lack of specificity. The most common first symptom and sign are progressive cognitive impairment and progressive dementia; however, the symptom spectrum and MRI imaging changes of white matter damage are related to age. MRI follow-up and targeted gene testing help reduce misdiagnosis and missed diagnosis of HDLS.

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Objective:To analyze the clinical characteristics of hereditary diffuse leukoencephalopathy with spheroids (HDLS).Methods:A retrospective analysis was performed. The clinical data of 2 patients with genetically conformed HDLS, admitted to our hospital in August 2020 and October 2021, were collected; and a literature search was conducted in domestic and foreign databases from January 2012 to January 2022 (enrolling a total of 48 patients with HDLS caused by colony-stimulating factor-1 receptor [ CSF1R] gene mutation). The population, clinical, imaging and gene mutation characteristics of these patients were summarized and analyzed. Results:(1) In these 50 patients, 20 were male and 30 were female, with onset age of (40.72±11.27) years; 40 patients (80.0%) had been misdiagnosed. (2) The most common first symptom and sign were progressive cognitive impairment (74.0%) and progressive dementia (80.0%). The patients in the middle and old aged group (≥40 years old, n=31) had significantly higher incidences of progressive cognitive impairment and Parkinson's-like symptom, and statistically lower incidence of muscle weakness as compared with those in the youth group (<40 years old, n=19, P<0.05). (3) The highest incidence of abnormal imaging findings was white matter lesions (100.0%), followed by cerebral atrophy (84.0%), ventricular enlargement (84.0%) and corpus callosum atrophy (60.0%). DWI examination was completed in 28 patients, and all patients showed persistent limitation of diffusion (100.0%). The most affected areas of white matter lesions were around the lateral ventricles, followed by the frontal-parietal occipital lobe, and corpus callosum. The incidence of abnormal signal of central semiovale in youth group was statistically higher than that in middle and old aged group ( P<0.05). (4) A total of 36 CSF1R gene mutations or possibly pathogenic mutations were identified in 50 patients, 21 of which were novel mutations reported for the first time. Of the 47 patients whose mutations were described in detail, 8 (17.0%) and 5 (10.6%) probands carried c. 2381T>C/p. I794T and c.2345G>A/p.R782H, respectively. Conclusions:The clinical manifestations of HDLS are diverse and lack of specificity. The most common first symptom and sign are progressive cognitive impairment and progressive dementia; however, the symptom spectrum and MRI imaging changes of white matter damage are related to age. MRI follow-up and targeted gene testing help reduce misdiagnosis and missed diagnosis of HDLS.

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Alzheimer's disease (AD) is one kind of degenerative diseases of the central nervous system, constituting a major social problem and economic threat around the world. Early diagnosis and intervention are the keys to its prevention and treatment. The traditional diagnosis system based on clinical experience and biomarkers has many limitations. A completely new "digital biomarkers" diagnostic system based on wearable devices is being constructed with the rapid development on artificial intelligence, 5G network and other technologies. This article will comprehensively describe the research progress on wearable devices which used to capture different cognitive-related signals such as memory, visual space, speech, executive functions in the construction of AD "digital biomarkers" diagnosis system, and forecast its application prospect in the future diagnosis, prevention and treatment of AD.

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Objective:To analyze the clinical characteristics of domestic sporadic Creutzfeldt-Jakob disease (sCJD).Methods:One patient diagnosed with probable sCJD in our hospital in October 2019 was firstly reported; the clinical data of this patient were retrospectively analyzed combining with those of 82 patients publicly reported in domestic core journals on China Biology Medicine disc, CNKI and WANFANG databases from 2009 to 2019 and met with MRI-CJD consortium criteria for sCJD.Results:Of the total 83 patients, 78 were diagnosed as clinically probable sCJD and other 5 as definite sCJD. There were 45 males and 38 females; the median age was 63 (58, 68) years. The course of disease was recorded in 56 patients, and the time from onset to death was 4.3 (2.9, 7.0) months. The onset and main symptoms were diverse and non-specific, however, progressive cognitive impairments, myoclonus, ataxia, visual dysfunction, akinetic mutism frequently occurred during the whole disease course. As compared with those in patients less than or equal to 65 years old, cerebellar symptoms and visual impairment occurred more frequently in patients over 65 years old ( P< 0.05). High diffusion weighted imaging (DWI) signals were detected on the cortex and/or the basal ganglia and/or the thalamus of 92.4% patients (73/79). Meanwhile, akinetic mutism was more likely to appear in patients with basal ganglia involvements than the unaffected ones (62.5% vs. 25.8%, P<0.05). Abnormal cortical DWI high signals in one patient were detected 7 months before the appearance of first symptom, and four patients who were clinically confirmed by dynamic follow-up DWI presented clinical symptoms highly corresponding to changes in DWI signals in brain regions. Conclusions:The sCJD tends to occur in the middle-aged and elderly patients, with high heterogeneity in clinical symptoms, durations and abnormal DWI signals, and symptoms caused by damage in posterior cranial fossa occur more frequently in patients over 65 years old; the DWI lesions in basal segment might be seen as a sign for deterioration of disease. Dynamic DWI follow-up may be helpful for early detection and objective reflection of sCJD intracerebral lesions.

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More and more evidences suggest that the gut-brain axis is comprehensively involved in the entire pathological courses of Alzheimer's disease (AD), and is a new source of its β-amyloid protein (Aβ) and tau pathologies and chronic inflammations in the brain. In this paper, the potential targets and application prospects in the prevention and treatment of AD are discussed from the aspects of gastrointestinal tract, intracerebral inflammation and intestinal flora.

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Almost all active immunotherapy attempts which targeted at clearing or reducing β-amyloid (Aβ) plaques in brains of patients with Alzheimer'disease (AD) were fallen into unprecedented difficulties,because of unsatisfactory curative effects.Recently,more and more evidences support that low density lipoprotein receptor related protein 1 (LRP1) is involved in Aβ production and clearance through multiple non-immune pathways,which has showed the potential as a whole-new interference target different with classical Aβ immunotherapies.So,we try to summarize the research developments of roles of LRP1 in Aβ metabolic process in physiological and AD conditions,and look forward to its possible applications in the prevention and treatment of AD.

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Objective To investigate the effects of low-fat diet or statin intervention at early age on brain amyloid β-protein (Aβ) pathology and behaviors of middle-aged Tg2576 mice.Methods Thirty-five two-month-old Tg2576 mice were randomly divided into following 5 groups:a juvenile statin group,a juvenile low-fat diet group,a young statin group,a young low-fat group,and a blank control group (n=7);mice in the low-fat diet groups were given standard low-fat feed,and mice in the statin group were given atorvastatin at 17 mg/(kg· d) into the normal diet.The initiation times of intervention were,respectively,set to be 2-month-old in juvenile groups and 6-month-old in young groups;meanwhile,mice in the blank-control group were fed with normal diet without statin.All mice were raised to be 10-month-old and tested by Morris water maze for evaluating cognitive behaviors two weeks before execution.After peripheral blood and brains being taken,a monoclonal anti-Aβ42 antibody was employed to immunostain mice brain paraffin tissue sections for assaying tissue Aβ plaque immunoreactivity (TAPIR),and the levels of Aβ40,Aβ42,β-secretase,and γ-secretase in homogenates were detected by enzyme-linked immunosorbent assays (ELISA).Results As compared with those in the blank-control group,the average escape latencies,times of passing through hidden platforms,percentage of strong TAPIR,Aβ42 and γ-secretase level in all intervention groups showed no statistical differences (P＞0.05).As compared with those in the blank control group,Aβ42 in homogenates of young intervention groups and β-secretase level in the young statin group were significantly higher (P＜0.05).Conclusion Interventions initiated from juvenile or young,and low-fat diet intervention or statin intervention can neither improve the mice's Morris water maze testing results,nor reduce Aβs burdens in brain homogenates and Aβ40 immunopathologies in brain tissues of middle-aged mice;over early initiation of low-fat diet intervention or statin intervention might accelerate or worsen Alzheimer's disease progress.

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The etiology and pathogenesis of Alzheimer's disease (AD) are still kept to be unknown;up to now,no method is proved to be effective and safe for its prevention and treatment.Recent data have shown that gut microbiota might participate in the onset and development of AD via a variety of pathways.From the perspective of gut microbiota,this review will retrospectively analyze the influence of gut microbiota on AD pathogenesis,outlook its application values of in preventing and treating AD.

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Objective To explore the effect of different types of statins combined with donepezil in the treatment of Alzheimer disease(AD).Methods According to the digital table,90 patients with AD were randomly divided into the statins A group(atrovstatin combined with donepezil) 31 cases,statins B group(simvastatin combined with donepezil)27 cases,and donepezil group(only with donepezil) 32 cases.All patients were treated for one year.The blood lipid level (including cholesterol (CH) and low density lipoprotein cholesterol (LDL-C),mini-mental state examination(MMSE),activity of daily living(ADL) and global deterioration scale (GDS) were detected and compared respectively among groups before and after treatment.Results The MMSE,ADL and GDS scores of the donepezil group were (17.00 ± 2.99) points,(60.44 ± 14.57) points,(4.28 ± 1.22) points,respectively,which were worse than those of the statins A group [(19.90 ± 3.07) points,(71.61 ± 18.50) points,(3.39 ± 1.15) points] (t =0.218,P ＜ 0.05,t =2.669,P ＜ 0.01,t =2.562,P ＜ 0.01) and statins B group [(19.88 ± 6.66) points,(71.89 ± 19.61) points,(3.37 ±l.39)points](t=l.959,P ＜0.05,t=2.991,P ＜0.0l,t=2,265,P ＜0.01).Conclusion The combination of donepezil and statins can effectively improve cognitive function and daily living ability in patients with AD,and its effect is superior to single use of donepezil.

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Missense point mutations, duplication and triplication in the alpha-synuclein (alphaSYN) gene have been identified in familial Parkinson's disease (PD). Familial and sporadic PD show common pathological features of alphaSYN pathologies, e.g., Lewy bodies (LBs) and Lewy neurites (LNs), and a loss of dopaminergic neurons in the substantia nigra that leads to motor disturbances. To elucidate the mechanism of alphaSYN pathologies, we generated TgalphaSYN transgenic mice overexpressing human alphaSYN with double mutations in A30P and A53T. Human alphaSYN accumulated widely in neurons, processes and aberrant neuronal inclusion bodies. Sarcosyl-insoluble alphaSYN, as well as phosphorylated, ubiquitinated and nitrated alphaSYN, was accumulated in the brains. Significantly decreased levels of dopamine (DA) were recognized in the striatum. Motor impairment was revealed in a rotarod test. Thus, TgalphaSYN is a useful model for analyzing the pathological cascade from aggregated alphaSYN to motor disturbance, and may be useful for drug trials.

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Encéfalo/metabolismo , Actividad Motora/fisiología , Neuronas/metabolismo , alfa-Sinucleína/genética , Acetilcolina/metabolismo , Animales , Western Blotting , Encéfalo/patología , Cuerpo Estriado/metabolismo , Dopamina/metabolismo , Humanos , Inmunohistoquímica , Cuerpos de Inclusión/metabolismo , Ratones , Ratones Transgénicos , Mutación , Neuronas/citología , Fosforilación , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Prueba de Desempeño de Rotación con Aceleración Constante , Serotonina/metabolismo , Ubiquitinación

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Abeta amyloidosis and tauopathy are characteristic changes in the brain of Alzheimer's disease. Although much evidence suggests that Abeta deposit is a critical initiation factor, the pathological pathway between Abeta amyloidosis and tau accumulation remains unclear. Tau accumulation was examined in the doubly transgenic mouse (APP-PS) expressing betaAPP(KM670/671NL) (Tg2576) and presenilin-1 L286V (PS-1 L286Vtg). Accelerated and enhanced Abeta amyloid deposits were detected from 8 weeks. Tau accumulation appeared at 4.5 months and markedly increased in dystrophic neurites around Abeta amyloid. Accumulated tau was phosphorylated, conformationally altered, and argyrophilic. Expression of tau and accumulation of sarkosyl-insoluble phosphorylated tau were increased in APP-PS brains compared with those of Tg2576 mice. Straight or twisted tubules mimicking paired helical filament were revealed at electron microscopic level in 16-month-old APP-PS. These findings suggest that mutant presenilin-1 accelerated Abeta-induced tauopathy and further promoted fibril formation of tau.

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Enfermedad de Alzheimer/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Encéfalo/metabolismo , Proteínas de la Membrana/metabolismo , Mutación/genética , Proteínas tau/metabolismo , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/fisiopatología , Precursor de Proteína beta-Amiloide/genética , Animales , Encéfalo/patología , Encéfalo/fisiopatología , Modelos Animales de Enfermedad , Proteínas de la Membrana/genética , Ratones , Ratones Transgénicos , Microscopía Electrónica de Transmisión , Microtúbulos/metabolismo , Microtúbulos/patología , Microtúbulos/ultraestructura , Neuritas/metabolismo , Neuritas/patología , Neuritas/ultraestructura , Ovillos Neurofibrilares/genética , Ovillos Neurofibrilares/metabolismo , Ovillos Neurofibrilares/patología , Fosforilación , Placa Amiloide/genética , Placa Amiloide/metabolismo , Placa Amiloide/patología , Presenilina-1 , Regulación hacia Arriba/genética

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0.05). ②Plasma endothelin in the two groups was remarkably decreased after treatment(P0.05).③ NO in the two groups was significantly increased after treatment(P0.05). Conclusion TFL can reduce blood pressure and improve endothelial cell function.

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Objective To explore the expression of naturally occurring plasma anti-? amyloid (A?) antibody in children and youngsters .Methods According to each 10 years, 28 healthy cases aged from 1~30 years old were diviedd to 3 groups.In the 3 groups,the plasma anti-A? antibody was detacted by immunostained with paraffin sections from Tg2576 mice brain to make a specific tissue amyloid plaque immunoreactivity (TAPIR) and immunoprecipitation analysis. Results The total occurrence rate of anti-A? antibody was 27.8%. There was no significant difference of TAPIR positive rate in each age group. They had the similar immunospecialties to middle-aged and elderly healthy controls. Conclusion Plasma anti-A? antibody can be occured before amyloid deposits and senile plaques in brain.