Decoding molecular mechanisms: brain aging and Alzheimer's disease.

The complex morphological, anatomical, physiological, and chemical mechanisms within the aging brain have been the hot topic of research for centuries. The aging process alters the brain structure that affects functions and cognitions, but the worsening of such processes contributes to the pathogenesis of neurodegenerative disorders, such as Alzheimer's disease. Beyond these observable, mild morphological shifts, significant functional modifications in neurotransmission and neuronal activity exert a crucial influence on the aging brain. Understanding these changes is important for maintaining cognitive health, especially given the increasing prevalence of age-related conditions that affect cognition. This review aims to explore the age-induced changes in brain plasticity and molecular processes, differentiating normal aging from the pathogenesis of Alzheimer's disease thereby providing insights into predicting the risk of dementia, particularly Alzheimer's disease.

Aging-Related Protein Alterations in the Brain.

Aging is an intrinsic aspect of an organism's life cycle and is characterized by progressive physiological decline and increased susceptibility to mortality. Many age-associated disorders, including neurological disorders, are most commonly linked with the aging process, such as Alzheimer's disease (AD). This review aims to provide a comprehensive overview of the effects of aging and AD on the molecular pathways and levels of different proteins in the brain, including metalloproteins, neurotrophic factors, amyloid proteins, and tau proteins. AD is caused by the aggregation of amyloid proteins in the brain. Factors such as metal ions, protein ligands, and the oligomerization state of amyloid precursor protein significantly influence the proteolytic processing of amyloid-ß protein precursor (AßPP). Tau, a disordered cytosolic protein, serves as the principal microtubule-associated protein in mature neurons. AD patients exhibit decreased levels of nerve growth factor within their nervous systems and cerebrospinal fluid. Furthermore, a significant increase in brain-derived neurotrophic factor resulting from the neuroprotective effect of glial cell line-derived neurotrophic factor suggests that the synergistic action of these proteins plays a role in inhibiting neuronal degeneration and atrophy. The mechanism through which Aß and AßPP govern Cu2+ transport and their influence on Cu2+ and other metal ion pools requires elucidation in future studies. A comprehensive understanding of the influence of aging and AD on molecular pathways and varying protein levels may hold the potential for the development of novel diagnostic and therapeutic methods for the treatment of AD.

Alzheimer's Behavioral and Psychiatric Burden in Saudi Arabia: Validation of the Saudi Version of the Neuropsychiatric Inventory.

BACKGROUND: The burden of behavioral and psychiatric symptoms in dementia (BPSD) has not been characterized in Saudi patients with Alzheimer disease (AD). Moreover, the Saudi version of the Neuropsychiatric Inventory (SNPI) has not been validated. OBJECTIVES: The purpose of this study was to validate the SNPI and describe frequency and determinants of BPSD in Saudi AD patients. METHODS: The SNPI and BEHAVE-AD instruments were administered to community-dwelling Saudi AD patients and their caregivers. RESULTS: The sample size was 192. The first 59 constituted the validation cohort. Cronbach alpha of the SNPI and BEHAVE-AD were 0.91 and 0.79, respectively. There were significant correlations between: (1) the total SNPI and BEHAVE-AD scores ( r =0.84, P <0.001); (2) analogous SNPI and BEHAVE-AD symptom subscores ( P <0.05); (3) SNPI and BEHAVE-AD caregiver distress ( F =22.6, P <0.001). Inter-rater reliability of the SNPI was excellent (kappa=0.74). Ninety percent of patients experienced 4 SNPI symptoms or more. Patients with stroke and prior psychiatric history were most likely to experience BPSDs. The most common symptom was apathy (82%). Caregiver distress was determined by the total NPI score and impulsiveness subscale score. CONCLUSIONS: The SNPI is valid and reliable for assessing BPSD in Saudi AD patients. Longitudinal studies of BPSDs in Saudi specialized dementia clinics are needed.

The future of alzheimer disease immunotherapies in Saudi Arabia: Consensus statement of the Saudi Chapter of Cognitive and Behavioral Neurology.

Alzheimer Disease (AD) constitutes a major global healthcare problem. Standard AD pharmacotherapies offer only modest transient cognitive and behavioral benefits. Aducanumab, an amyloid monoclonal antibody, was the first disease modifying agent to be approved for AD treatment. However, concerns about its efficacy and side effects led regulatory institutions around the world to restrict its use. Lecanemab was the second amyloid antibody to receive accelerated approval for use in early AD. This review and consensus statement was prepared by the Saudi Chapter of Cognitive and Behavioral Neurology to review the current developments in AD immunotherapies from a Saudi perspective. We outline recommendations with regards to offering aducanumab and other future immunotherapies to Saudi AD patients. We describe resources, infrastructure, research, and clinical practice changes that must be attained to transform the patient journey and clinical pathways of AD in Saudi Arabia to enable offering AD immunotherapies in Saudi Arabia.

Neuroeconomics of decision-making during COVID-19 pandemic.

The coronavirus disease 2019 (COVID-19) pandemic reveals the decision-making challenges faced by communities, governments, and international organizations, globally. Policymakers are much concerned about protecting the population from the deadly virus while lacking reliable information on the virus and its spread mechanisms and the effectiveness of possible measures and their (direct and indirect) health and socioeconomic costs. This review aims to highlight the various balanced policy decision that would combine the best obtainable scientific evidence characteristically provided by expert opinions and modeling studies. This article's main goal is to summarize the main significant progress in the understanding of neuroeconomics of decision-making and discuss the anatomy of decision making in the light of COVID-19 pandemic.

Effects of transcranial magnetic stimulation on neurobiological changes in Alzheimer's disease (Review).

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive decline and brain neuronal loss. A pioneering field of research in AD is brain stimulation via electromagnetic fields (EMFs), which may produce clinical benefits. Noninvasive brain stimulation techniques, such as transcranial magnetic stimulation (TMS), have been developed to treat neurological and psychiatric disorders. The purpose of the present review is to identify neurobiological changes, including inflammatory, neurodegenerative, apoptotic, neuroprotective and genetic changes, which are associated with repetitive TMS (rTMS) treatment in patients with AD. Furthermore, it aims to evaluate the effect of TMS treatment in patients with AD and to identify the associated mechanisms. The present review highlights the changes in inflammatory and apoptotic mechanisms, mitochondrial enzymatic activities, and modulation of gene expression (microRNA expression profiles) associated with rTMS or sham procedures. At the molecular level, it has been suggested that EMFs generated by TMS may affect the cell redox status and amyloidogenic processes. TMS may also modulate gene expression by acting on both transcriptional and post­transcriptional regulatory mechanisms. TMS may increase brain cortical excitability, induce specific potentiation phenomena, and promote synaptic plasticity and recovery of impaired functions; thus, it may re­establish cognitive performance in patients with AD.

The Arabic Translation and Cross-Cultural Adaptation of the Bristol Activity of Daily Living Scale.

BACKGROUND: There are few Arabic language functional scales for patients with dementia. The Bristol Activity of Daily Living Scale (BADLS) was designed and validated for use in patients with dementia. OBJECTIVE: Our study aimed to translate, cross-culturally adapt, and validate the BADLS to the Arabic language for people with neurocognitive decline and dementia. METHODS: The original BADLS scale was translated to the Arabic language followed by face validity assessment through a pilot testing in five Arabic countries. The Arabic BADLS was assessed in a sample of 139 participants and their caregivers for concurrent and convergent validity. RESULTS: The Arabic BADLS had excellent internal consistency, Cronbach's alpha 0.95 (95% CI 0.93-0.96). Likewise, the Arabic BADLS had strong convergent validity with the Montreal Cognitive Assessment (r = -0.82, p < 0.001). CONCLUSION: The Arabic BADLS is a valid scale that can used to assess the functional performance of people living with dementia.

Genetic and epigenetic study of an Alzheimer's disease family with monozygotic triplets.

Age at onset of Alzheimer's disease is highly variable, and its modifiers (genetic or environmental) could act through epigenetic changes, such as DNA methylation at CpG sites. DNA methylation is also linked to ageing-the strongest Alzheimer's disease risk factor. DNA methylation age can be calculated using age-related CpGs and might reflect biological ageing. We conducted a clinical, genetic and epigenetic investigation of a unique Ashkenazi Jewish family with monozygotic triplets, two of whom developed Alzheimer's disease at ages 73 and 76, while the third at age 85 has no cognitive complaints or deficits in daily activities. One of their offspring developed Alzheimer's disease at age 50. Targeted sequencing of 80 genes associated with neurodegeneration revealed that the triplets and the affected offspring are heterozygous carriers of the risk APOE ε4 allele, as well as rare substitutions in APP (p.S198P), NOTCH3 (p.H1235L) and SORL1 (p.W1563C). In addition, we catalogued 52 possibly damaging rare variants detected by NeuroX array in affected individuals. Analysis of family members on a genome-wide DNA methylation chip revealed that the DNA methylation age of the triplets was 6-10 years younger than chronological age, while it was 9 years older in the offspring with early-onset Alzheimer's disease, suggesting accelerated ageing.