BACKGROUNDS: Behavioral and psychological symptoms as well as cognitive impairement are very disturbing symptoms in dementia. It is important in managing dementia patient to control these behavioral and psychological symptoms. In this study, we examined the effect of risperidone and optimal therapeutic dosage on controlling these behavioral and psychological symptoms of dementia (BPSD). METHODS: 57 patients (male: 19, female: 38) with dementia, aged 65 and older in Buyeo geriatric hospital located in Buyeo-gun, chung-nam, were finally included in this study. risperidone was administrated to these subjects for 10 weeks to control BPSD. Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD) was rated before administration of risperidone and after administration of risperidone for 10 weeks to evaluate the improvement of BPSD. Global Deterioration Scale (GDS) was rated before administration of risperidone. The correlation between baseline GDS score and the change of sum score of BEHAVE-AD was analyzed. RESULT: The mean dose of resperidone at the endpoint was 0.706+/-0.522 mg/d. The significant reduction of the sum score of BEHAVE-AD was observed in subjects after administration of risperidone for 10 weeks. Clinical improvement (> or =50% reduction of sum score of BEHAVE-AD from baseline sum score) was showed in 32 subjects (56.1%) among 57 subjects. Also there was weakly negative correlation between baseline GDS score and the change of sum score of BEHAVE0AD. CONCLUSION: Risperidone was effective in controlling BPSD of dementia patients at 0.706+/-0.522 mg/d.
Alzheimer Disease ; Dementia* ; Female ; Humans ; Pathology ; Risperidone*

Audiovisual integration is a vital information process involved in cognition and is closely correlated with aging and Alzheimer's disease (AD). In this review, we evaluated the altered audiovisual integrative behavioral symptoms in AD. We further analyzed the relationships between AD pathologies and audiovisual integration alterations bidirectionally and suggested the possible mechanisms of audiovisual integration alterations underlying AD, including the imbalance between energy demand and supply, activity-dependent degeneration, disrupted brain networks, and cognitive resource overloading. Then, based on the clinical characteristics including electrophysiological and imaging data related to audiovisual integration, we emphasized the value of audiovisual integration alterations as potential biomarkers for the early diagnosis and progression of AD. We also highlighted that treatments targeted audiovisual integration contributed to widespread pathological improvements in AD animal models and cognitive improvements in AD patients. Moreover, investigation into audiovisual integration alterations in AD also provided new insights and comprehension about sensory information processes.
Animals ; Humans ; Alzheimer Disease/pathology* ; Brain/pathology* ; Aging/physiology* ; Cognition

Alzheimer Disease ; pathology ; Drugs, Chinese Herbal ; pharmacology ; Humans ; Rhodiola

Our previous studies proposed that Alzheimer's disease (AD) is a metabolic disorder and hypothesized that abnormal brain glucose metabolism inducing multiple pathophysiological cascades contributes to AD pathogenesis. Aging is one of the great significant risk factors for AD. Membrane aging is first prone to affect the function and structure of the brain by impairing glucose metabolism. We presume that risk factors of AD, including genetic factors (e.g., the apolipoprotein E ε4 allele and genetic mutations) and non-genetic factors (such as fat, diabetes, and cardiac failure) accelerate biomembrane aging and lead to the onset and development of the disease. In this review, we further modify our previous hypothesis to demonstrate "membrane aging" as an initial pathogenic factor that results in functional and structural alterations of membranes and, consequently, glucose hypometabolism and multiple pathophysiological cascades.
Aging ; pathology ; Alzheimer Disease ; etiology ; pathology ; Animals ; Brain ; pathology ; Cell Membrane ; pathology ; Humans

Alzheimer Disease/pathology* ; Animals ; C9orf72 Protein/metabolism* ; Mice ; Microglia/pathology* ; Neuronal Plasticity ; Neurons/pathology* ; Synapses/pathology*

With the intensified aging problem, the study of age-related diseases is becoming more and more significant. Alzheimer's disease is a kind of dementia, with senile plaques and neurofibrillary tangles as the main pathological features, and has become one of the major diseases that endanger the health of the elderly. This review is concentrated on the research of the early assessment of Alzheimer's disease. The current situation of early diagnosis of the disease is analyzed, and a prospect of the future development of early assessment means of the disease is also made in the paper.
Aged ; Aging ; Alzheimer Disease ; diagnosis ; pathology ; Early Diagnosis ; Humans ; Neurofibrillary Tangles ; pathology ; Plaque, Amyloid ; pathology

No disease-modifying therapies (DMT) for neurodegenerative diseases (NDs) have been established, particularly for Alzheimer's disease (AD) and Parkinson's disease (PD). It is unclear why candidate drugs that successfully demonstrate therapeutic effects in animal models fail to show disease-modifying effects in clinical trials. To overcome this hurdle, patients with homogeneous pathologies should be detected as early as possible. The early detection of AD patients using sufficiently tested biomarkers could demonstrate the potential usefulness of combining biomarkers with clinical measures as a diagnostic tool. Cerebrospinal fluid (CSF) biomarkers for NDs are being incorporated in clinical trials designed with the aim of detecting patients earlier, evaluating target engagement, collecting homogeneous patients, facilitating prevention trials, and testing the potential of surrogate markers relative to clinical measures. In this review we summarize the latest information on CSF biomarkers in NDs, particularly AD and PD, and their use in clinical trials. The large number of issues related to CSF biomarker measurements and applications has resulted in relatively few clinical trials on CSF biomarkers being conducted. However, the available CSF biomarker data obtained in clinical trials support the advantages of incorporating CSF biomarkers in clinical trials, even though the data have mostly been obtained in AD trials. We describe the current issues with and ongoing efforts for the use of CSF biomarkers in clinical trials and the plans to harness CSF biomarkers for the development of DMT and clinical routines. This effort requires nationwide, global, and multidisciplinary efforts in academia, industry, and regulatory agencies to facilitate a new era.
Alzheimer Disease ; Biomarkers* ; Cerebrospinal Fluid* ; Humans ; Models, Animal ; Neurodegenerative Diseases ; Parkinson Disease ; Pathology ; Therapeutic Uses

The accumulation and spread of prion-like proteins is a key feature of neurodegenerative diseases (NDs) such as Alzheimer's disease, Parkinson's disease, or Amyotrophic Lateral Sclerosis. In a process known as 'seeding', prion-like proteins such as amyloid beta, microtubule-associated protein tau, α-synuclein, silence superoxide dismutase 1, or transactive response DNA-binding protein 43 kDa, propagate their misfolded conformations by transforming their respective soluble monomers into fibrils. Cellular and molecular evidence of prion-like propagation in NDs, the clinical relevance of their 'seeding' capacities, and their levels of contribution towards disease progression have been intensively studied over recent years. This review unpacks the cyclic prion-like propagation in cells including factors of aggregate internalization, endo-lysosomal leaking, aggregate degradation, and secretion. Debates on the importance of the role of prion-like protein aggregates in NDs, whether causal or consequent, are also discussed. Applications lead to a greater understanding of ND pathogenesis and increased potential for therapeutic strategies.
Humans ; Prions ; Neurodegenerative Diseases/pathology* ; Amyloid beta-Peptides ; Alzheimer Disease ; alpha-Synuclein ; tau Proteins ; Parkinson Disease

OBJECTIVE: We hypothesized that prominent pulvinar hypointensity in brain MRI represents the disease process due to iron accumulation in Alzheimer disease (AD). We aimed to determine whether or not the pulvinar signal intensity (SI) on the fluid-attenuated inversion recovery (FLAIR) sequences at 3.0T MRI differs between AD patients and normal subjects, and also whether the pulvinar SI is correlated with the T2* map, an imaging marker for tissue iron, and a cognitive scale. MATERIALS AND METHODS: Twenty one consecutive patients with AD and 21 age-matched control subjects were prospectively included in this study. The pulvinar SI was assessed on the FLAIR image. We measured the relative SI ratio of the pulvinar to the corpus callosum. The T2* values were calculated from the T2* relaxometry map. The differences between the two groups were analyzed, by using a Student t test. The correlation between the measurements was assessed by the Pearson's correlation test. RESULTS: As compared to the normal white matter, the FLAIR signal intensity of the pulvinar nucleus was significantly more hypointense in the AD patients than in the control subjects (p < 0.01). The pulvinar T2* was shorter in the AD patients than in the control subjects (51.5 +/- 4.95 ms vs. 56.5 +/- 5.49 ms, respectively, p = 0.003). The pulvinar SI ratio was strongly correlated with the pulvinar T2* (r = 0.745, p < 0.001). When controlling for age, only the pulvinar-to-CC SI ratio was positively correlated with that of the Mini-Mental State Examination (MMSE) score (r = 0.303, p < 0.050). Conversely, the pulvinar T2* was not correlated with the MMSE score (r = 0.277, p = 0.080). CONCLUSION: The FLAIR hypointensity of the pulvinar nucleus represents an abnormal iron accumulation in AD and may be used as an adjunctive finding for evaluating AD.
Aged ; Alzheimer Disease/*metabolism/*pathology ; Female ; Humans ; Iron/*metabolism ; *Magnetic Resonance Imaging ; Male ; Pulvinar/metabolism/*pathology

OBJECTIVETo examine cerebral pathologies in cerebral amyloid angiopathy in a rat model of Alzheimer's disease.

METHODSRat models of Alzheimer's disease was established by stereotactic Aβ1-42 fiber injection in the bilateral hippocampus. The cognitive function of the rats was evaluated with water maze test. HE staining, Congo red staining and double-labeling indirect immunofluorescence were used to examine the dynamic distribution of Aβ fiber deposit in the brain.

RESULTSThe model rats showed significant differences from the control rats in the escape latency and the times of crossing platform in waster maze test. HE staining revealed a decreased number and degeneration of the granular cells with increased glial cells in the model rats. Congo Red staining showed that the Aβ fiber was deposited gradually in the small vessels in the brain parenchyma to cause thickening, stenosis or occlusion of the small vessels. Immunofluorescence staining detected Aβ fiber migration from the parenchyma to the walls of the small arteries in the rat models.

CONCLUSIONCerebral amyloid angiopathy is a major pathological feature in Alzheimer's disease.

Alzheimer Disease ; pathology ; Amyloid beta-Peptides ; chemistry ; Animals ; Brain ; pathology ; Cerebral Amyloid Angiopathy ; pathology ; Disease Models, Animal ; Rats ; Staining and Labeling