Dystonia is a neurological disease that is currently ranked as the third most common motor disorder. Patients exhibit repetitive and sometimes sustained muscle contractions that cause limb and body twisting and abnormal postures that impair movement. Deep brain stimulation (DBS) of the basal ganglia and thalamus can be used to improve motor function when other treatment options fail. Recently, the cerebellum has garnered interest as a DBS target for treating dystonia and other motor disorders. Here, we describe a procedure for targeting DBS electrodes to the interposed cerebellar nuclei to correct motor dysfunction in a mouse model with dystonia. Targeting cerebellar outflow pathways with neuromodulation opens new possibilities for using the expansive connectivity of the cerebellum to treat motor and non-motor diseases.
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http://dx.doi.org/10.1007/978-3-031-26220-3_6 | DOI Listing |
Lecanemab, a humanized IgG1 monoclonal antibody that binds with high affinity to amyloid-beta (Aβ) protofibrils, was formally evaluated as a treatment for early Alzheimer's disease in a phase 2 study (Study 201) and the phase 3 Clarity AD study. These trials both included an 18-month, randomized study (core) and an open-label extension (OLE) phase where eligible participants received open-label lecanemab for up to 30 months to date. Clinical (CDR-SB, ADAS-Cog14, and ADCS-MCI-ADL), biomarker (PET, Aβ42/40 ratio, and ptau181) and safety outcomes were evaluated.
View Article and Find Full Text PDFBackground: The increased incidence of Alzheimer's disease (AD) rate represent an unmet medical need and thus critical for the development of novel molecular therapeutics. Recent work focusing on patients with apoE4 alleles has highlighted the association of brain cholesterol dysregulation with elevated pathological burden and neurodegeneration. These studies have highlighted the importance of the nuclear receptor Liver X receptor (LXR) for developing AD therapies.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Relecura, Bangalore, karnataka, India.
Background: Clinical Dementia Rating (CDR) and its evaluation have been important nowadays as its prevalence in older ages after 60 years. Early identification of dementia can help the world to take preventive measures as most of them are treatable. The cellular Automata (CA) framework is a powerful tool in analyzing brain dynamics and modeling the prognosis of Alzheimer's disease.
View Article and Find Full Text PDFBackground: Lecanemab is a humanized IgG1 monoclonal antibody that binds with high affinity to Aβ soluble protofibrils. In two clinical study evaluations of lecanemab, Clarity AD (NCT03887455) and lecanemab phase 2 study (Study 201, NCT01767311), the drug showed statistically significant reduction in disease progression during 18 months of treatment relative to placebo. Anti-amyloid immunotherapy can result in higher rates of "pseudo-atrophy" (ie, whole brain volume loss or ventricular enlargement) relative to disease progression observed in placebo-treated subjects.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Memory and Aging Center, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.
Women account for almost two-thirds of Alzheimer's disease (AD) cases, yet evidence significantly less clinical benefit from recently deployed amyloid-lowering therapies. To close this disparity gap, there is an urgent need to identify biological drivers of sex differences in the manifestation and clinical response to AD therapeutics. A recent review of multi-omic studies of AD reported >75% of studies showed female-specific changes at the molecular level (vs.
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