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Cognitive complaints are common in elderly subjects and are a frequent reason for referral to memory clinics. If the complaints are not associated with objective cognitive impairment, the condition is labelled subjective cognitive decline (SCD). SCD is often considered as a stage antedating objective impairment, and an at-risk condition for subsequent dementia. Recent large-scale studies indicate that a significantly increased risk of clinical progression in subjects with SCD is associated with positivity for Alzheimer's disease (AD) biomarkers, a finding supporting the notion that SCD can be due to different mechanisms not associated with neurodegeneration, including functional cognitive disorders. In this paper we present a selective review of research on the relations among SCD, cognitive awareness, and metacognitive abilities. We propose that longitudinal studies of metacognitive efficiency in SCD may provide useful cues about the risk of progression to dementia and the possible presence of a functional cognitive disorder, with different implications for the management of this prevalent aging-related condition. HIGHLIGHTS: Subjective cognitive decline (SCD), a common cause of referral to memory clinics, can be due to multiple conditions. The predictive value of SCD for progression to Alzheimer's disease (AD) dementia is high in association with AD biomarker positivity. The awareness of cognitive decline is the mechanism responsible for the emergence of SCD and metacognition is the underlying neuropsychological function. The awareness of cognitive decline in clinical patients is usually assessed comparing an informant rating to the patient self-assessment, a method that can be affected by informant bias. While there is strong evidence that awareness starts to decline with the onset of objective cognitive impairment, progressively leading to the anosognosia of AD, the status of metacognitive efficiency in SCD needs to be further investigated. Quantitative, performance-based indexes of metacognitive efficiency may contribute both to the assessment of progression risk and to the management of subjects with functional cognitive disorders.
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http://dx.doi.org/10.1002/alz.13905 | DOI Listing |
CNS Drugs
September 2025
Global Health Neurology Lab, Sydney, NSW, 2150, Australia.
Acute ischemic stroke (AIS) remains a leading cause of mortality and long-term disability globally, with survivors at high risk of recurrent stroke, cardiovascular events, and post-stroke dementia. Statins, while widely used for their lipid-lowering effects, also possess pleiotropic properties, including anti-inflammatory, endothelial-stabilizing, and neuroprotective actions, which may offer added benefit in AIS management. This article synthesizes emerging evidence on statins' dual mechanisms of action and evaluates their role in reducing recurrence, improving survival, and mitigating cognitive decline.
View Article and Find Full Text PDFPsychopharmacology (Berl)
September 2025
División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Ciudad Universitaria, Mexico City, 04510, Mexico.
Rationale: One of the earliest changes associated with Alzheimer's disease (AD) is the loss of catecholaminergic terminals in the cortex and hippocampus originating from the Locus Coeruleus (LC). This decline leads to reduced catecholaminergic neurotransmitters in the hippocampus, affecting synaptic plasticity and spatial memory. However, it is unclear whether restoring catecholaminergic transmission in the terminals from the LC may alleviate the spatial memory deficits associated with AD.
View Article and Find Full Text PDFNaunyn Schmiedebergs Arch Pharmacol
September 2025
Pharmacology and Toxicology Department, Faculty of Pharmacy and Biotechnology, German University in Cairo, Gamal Abdel Nasser, 11835, New Cairo, Egypt.
Licochalcone A (LCA), a natural flavonoid with potent anti-inflammatory properties, has shown promise as a neuroprotective agent. However, its ability to cross the blood-brain barrier (BBB) and exert central effects remains underexplored. In this study, we demonstrate for the first time that LCA enhances cognitive function in a lipopolysaccharide (LPS)-induced neuroinflammatory mouse model and effectively penetrates the BBB.
View Article and Find Full Text PDFRadiology
September 2025
Department of Radiology and Radiological Sciences, Johns Hopkins University, Baltimore, Md.
Background Elevated brain iron is a potential marker for neurodegeneration, but its role in predicting onset of mild cognitive impairment (MCI) and prospective cognitive trajectories remains unclear. Purpose To investigate how brain iron and amyloid-β (Aβ) levels, measured using quantitative susceptibility mapping (QSM) MRI and PET, help predict MCI onset and cognitive decline. Materials and Methods In this prospective study conducted between January 2015 and November 2022, cognitively unimpaired older adults underwent baseline QSM MRI.
View Article and Find Full Text PDFAging Cell
September 2025
Department of Cell Systems & Anatomy, University of Texas Health San Antonio, San Antonio, Texas, USA.
The Hippo signaling pathway is a key regulator of cell growth and cell survival, and hyperactivation of the Hippo pathway has been implicated in neurodegenerative diseases such as Huntington's disease. However, the role of Hippo signaling in Alzheimer's disease (AD) remains unclear. We observed that hyperactivation of Hippo signaling occurred in the AD model 5xFAD mice.
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