Background: Although individualized models using demographic, MRI, and biological markers have recently been applied in mild cognitive impairment (MCI), a similar study is lacking for patients with early Alzheimer's disease (AD) with biomarker evidence of abnormal amyloid in the brain.
Objective: We aimed to develop prognostic models for individualized prediction of cognitive change in early AD.
Methods: A total of 421 individuals with early AD (MCI or mild dementia due to AD) having biomarker evidence of abnormal amyloid in the brain were included in the current study. The primary cognitive outcome was the slope of change in Alzheimer's Disease Assessment Scale-cognitive subscale-13 (ADAS-Cog-13) over a period of up to 5 years.
Results: A model combining demographics, baseline cognition, neurodegenerative markers, and CSF AD biomarkers provided the best predictive performance, achieving an overfitting-corrected R of 0.59 (bootstrapping validation). A nomogram was created to enable clinicians or trialists to easily and visually estimate the individualized magnitude of cognitive change in the context of patient characteristics. Simulated clinical trials suggested that the inclusion of our nomogram into the enrichment strategy would lead to a substantial reduction of sample size in a trial of early AD.
Conclusions: Our findings may be of great clinical relevance to identify individuals with early AD who are likely to experience fast cognitive deterioration in clinical practice and in clinical trials.
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http://dx.doi.org/10.3233/ADR-240049 | DOI Listing |
J Biomol Struct Dyn
December 2024
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Biruni University, Istanbul, Türkiye.
The increasing global prevalence of Alzheimer's disease necessitates the development of novel therapeutic approaches. Neurodegenerative diseases are associated with increased oxidative stress and levels of cholinesterase enzymes. Hence, the development of cholinesterase inhibitors and antioxidants may provide neuroprotective effects.
View Article and Find Full Text PDFZh Nevrol Psikhiatr Im S S Korsakova
December 2024
Federal Center of Brain Research and Neurotechnologies, Moscow, Russia.
Objective: Study of neuroimaging changes according to MRI morphometry and their comparison with the structure and severity of cognitive impairment (CI) in patients with Alzheimer's disease (AD) and primary open-angle glaucoma (POAG).
Material And Methods: The study involved 90 patients who were divided into two equal groups of 45 people and who early had diagnosis of AD (group 1; median age - 71 [66; 77] years) and POAG (group 2; median age - 68 [64; 77] years). 71] years).
Zh Nevrol Psikhiatr Im S S Korsakova
December 2024
Mental Health Research Center, Moscow, Russia.
Mental disorders are complex illnesses with multifactorial etiologies involving genetic and environmental components. This review focuses on cellular models derived from the olfactory epithelium as a promising tool to study the molecular mechanisms of some neuropsychiatric diseases. The authors consider cell lines allowing the identification of potential biomarkers and pathogenetic mechanisms of schizophrenia, bipolar disorder, and Alzheimer's disease.
View Article and Find Full Text PDFArch Pharm (Weinheim)
January 2025
Department of Pharmacognosy, University Institute of Pharma Sciences, Chandigarh University, Mohali, Punjab, India.
Alzheimer's disease (AD) is a prevalent neurological illness that affects over 80% of aged adults globally in cases of dementia. Although the exact pathophysiological causes of AD remain unclear, its pathogenesis is primarily driven by several distinct biochemical alterations: (i) the accumulation of toxic Aβ plaques, (ii) the hyperphosphorylation of tau proteins, (iii) oxidative stress resulting in cell death, and (iv) an imbalance between the two main neurotransmitters, glutamate and acetylcholine (ACh). Currently, there are very few medications available and no treatment.
View Article and Find Full Text PDFJpn J Radiol
December 2024
Department of Radiology, Mie University Graduate School of Medicine, 2-174, Edobashi, Tsu, Mie, 514-8507, Japan.
Cerebral amyloid angiopathy (CAA) is an age-related small vessel disease pathologically characterized by the progressive accumulation of amyloid-beta (Aβ) peptide in cerebrovascular walls, affecting both cortical and leptomeningeal vessels. Amyloid deposition results in fragile vessels, which may lead to lobar intracerebral hemorrhage (ICH) and cognitive impairment. To evaluate the probability and severity of CAA, the imaging markers depicted on CT and MRI techniques are crucial, as brain pathological examination is highly invasive.
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