Dissociable effect of different measures of Vascular Metrics on Cognitive Function: The Mediating role of the Thalamic Subregions.

Background: The impact of white matter hyperintensities (WMH) on cognitive performance is uncertain due to inconsistent findings. The thalamus is of particular interest given its susceptibility to vascular damage. To test how different vascular risks (Deep/Periventricular WMH and Vascular Scores (VS)) affect thalamic subregional volumes and whether that has any mediating effect on different cognitive domains in healthy controls, mild cognitive impairment (MCI) and AD.

Exploring Polygenic Risk and Neuroimaging Parameters across the Alzheimer's disease Spectrum.

Background: Sporadic Alzheimer’s disease (AD) accounts for >90% of AD cases, of which 70% are thought to be due to a combination of several risk genes. Of these, Apolipoprotein E (APOE) is the most studied gene. Given that the APOE ɛ4 risk variant is found in ∼14% of the general population and ∼37% of the AD population, APOE ɛ4 is neither necessary nor sufficient to cause AD on its own.

Cerebral perfusion alterations in healthy young adults due to two genetic risk factors of Alzheimer's disease: APOE and MAPT.

Functional brain changes such as altered cerebral blood flow occur long before the onset of clinical symptoms in Alzheimer's disease (AD) and other neurodegenerative disorders. While cerebral hypoperfusion occurs in established AD, middle-aged carriers of genetic risk factors for AD, including APOE ε4, display regional hyperperfusion due to hypothesised pleiotropic or compensatory effects, representing a possible early biomarker of AD and facilitating earlier AD diagnosis. However, it is not clear whether hyperperfusion already exists even earlier in life.

The Contribution of Cognitive Control Networks in Word Selection Processing in Parkinson's Disease: Novel Insights from a Functional Connectivity Study.

Parkinson's disease (PD) patients are impaired in word production when the word has to be selected among competing alternatives requiring higher attentional resources. In PD, word selection processes are correlated with the structural integrity of the inferior frontal gyrus, which is critical for response selection, and the uncinate fasciculus, which is necessary for processing lexical information. In early PD, we investigated the role of the main cognitive large-scale networks, namely the salience network (SN), the central executive networks (CENs), and the default mode network (DMN), in word selection.

Increasing hexokinase 1 expression improves mitochondrial and glycolytic functional deficits seen in sporadic Alzheimer's disease astrocytes.

Abnormalities in cellular metabolism are seen early in Alzheimer's disease (AD). Astrocyte support for neuronal function has a high metabolic demand, and astrocyte glucose metabolism plays a key role in encoding memory. This indicates that astrocyte metabolic dysfunction might be an early event in the development of AD.

Highly Superior Autobiographical Memory (HSAM): A Systematic Review.

Individuals possessing a Highly Superior Autobiographical Memory (HSAM) demonstrate an exceptional ability to recall their own past, excelling most when dates from their lifetime are used as retrieval cues. Fully understanding how neurocognitive mechanisms support exceptional memory could lead to benefits in areas of healthcare in which memory plays a central role and in legal fields reliant on witnesses' memories. Predominantly due to the rareness of the phenomenon, existing HSAM literature is highly heterogenous in its methodologies used.

APOE ε4 positivity predicts centrality of episodic memory nodes in patients with mild cognitive impairment: A cohort-based, graph theory-informed study of cognitive networks.

As network neuroscience can capture the systemic impact of APOE variability at a neuroimaging level, this study investigated the network-based cognitive endophenotypes of ε4-carriers and non-carriers across the continuum between normal ageing and Alzheimer's dementia (AD). We hypothesised that the impact of APOE-ε4 on cognitive functioning can be reliably captured by the measurement of graph-theory centrality. Cognitive networks were calculated in 8118 controls, 3482 MCI patients and 4573 AD patients, recruited in the National Alzheimer's Coordinating Center (NACC) database.

Resting-state functional connectivity is modulated by cognitive reserve in early Parkinson's disease.

Background: Fronto-striatal disconnection is thought to be at the basis of dysexecutive symptoms in patients with Parkinson's disease (PD). Multiple reserve-related processes may offer resilience against functional decline. Among these, cognitive reserve (CR) refers to the adaptability of cognitive processes.

The effect of physical activity on white matter integrity in aging and prodromal to mild Alzheimer's disease with vascular comorbidity.

Background: Physical activity is a modifiable lifestyle factor that has been previously associated with reduced vascular burden and reduced risk of dementia.

Objectives: This study tested whether physical activity (i.e.

Identification of Regulatory Molecular "Hot Spots" for LH/PLOD Collagen Glycosyltransferase Activity.

Hydroxylysine glycosylations are post-translational modifications (PTMs) essential for the maturation and homeostasis of fibrillar and non-fibrillar collagen molecules. The multifunctional collagen lysyl hydroxylase 3 (LH3/PLOD3) and the collagen galactosyltransferase GLT25D1 are the human enzymes that have been identified as being responsible for the glycosylation of collagen lysines, although a precise description of the contribution of each enzyme to these essential PTMs has not yet been provided in the literature. LH3/PLOD3 is thought to be capable of performing two chemically distinct collagen glycosyltransferase reactions using the same catalytic site: an inverting beta-1,O-galactosylation of hydroxylysines (Gal-T) and a retaining alpha-1,2-glucosylation of galactosyl hydroxylysines (Glc-T).

Sex differences in olfactory cortex neuronal loss in aging.

Introduction: Aging plays a major role in neurodegenerative disorders such as Alzheimer's disease, and impacts neuronal loss. Olfactory dysfunction can be an early alteration heralding the presence of a neurodegenerative disorder in aging. Studying alterations in olfaction-related brain regions might help detection of neurodegenerative diseases at an earlier stage as well as protect individuals from any danger caused by loss of sense of smell.

Item-Level Scores on the Boston Naming Test as an Independent Predictor of Perirhinal Volume in Individuals with Mild Cognitive Impairment.

We explored the methodological value of an item-level scoring procedure applied to the Boston Naming Test (BNT), and the extent to which this scoring approach predicts grey matter (GM) variability in regions that sustain semantic memory. Twenty-seven BNT items administered as part of the Alzheimer's Disease Neuroimaging Initiative were scored according to their "sensorimotor interaction" (SMI) value. Quantitative scores (i.

Current Understanding of Verbal Fluency in Alzheimer's Disease: Evidence to Date.

Since their development, verbal fluency tests (VFTs) have been used extensively throughout research and in clinical settings to assess a variety of cognitive functions in diverse populations. In Alzheimer's disease (AD), these tasks have proven particularly valuable in identifying the earliest forms of cognitive decline in semantic processing and have been shown to relate specifically to brain regions associated with the initial stages of pathological change. In recent years, researchers have developed more nuanced techniques to evaluate verbal fluency performance, extracting a wide range of cognitive metrics from these simple neuropsychological tests.

A Fe-dependent self-inhibited state influences the druggability of human collagen lysyl hydroxylase (LH/PLOD) enzymes.

Multifunctional human collagen lysyl hydroxylase (LH/PLOD) enzymes catalyze post-translational hydroxylation and subsequent glycosylation of collagens, enabling their maturation and supramolecular organization in the extracellular matrix (ECM). Recently, the overexpression of LH/PLODs in the tumor microenvironment results in abnormal accumulation of these collagen post-translational modifications, which has been correlated with increased metastatic progression of a wide variety of solid tumors. These observations make LH/PLODs excellent candidates for prospective treatment of aggressive cancers.

Verbal fluency discrepancies as a marker of the prehippocampal stages of Alzheimer's disease.

Objective: Prior to evidence of episodic memory decline, a lengthy preclinical phase of Alzheimer's disease (AD) exists characterized by the build-up of tau pathology within extrahippocampal structures. Semantic memory, also impaired in AD, has been linked to degradation within these earliest affected areas. This study aimed to assess the utility of performance discrepancies between letter and category verbal fluency tasks to detect neuronal loss in brain regions affected very early by AD.

The Impact of Social Isolation Due to COVID-19 on Symptom Progression in People With Dementia: Findings of the SOLITUDE Study.

Background: People with dementia (PWD) are vulnerable to abrupt changes to daily routines. The lockdown enforced on the 23rd of March 2020 in the UK to contain the expansion of the COVID-19 pandemic limited opportunities for PWD to access healthcare services and socialise. The SOLITUDE study explored the potential long-term effects of lockdown on PWD's symptoms and carers' burden.

The impact of social isolation due to the COVID-19 pandemic on patients with dementia and caregivers.

Objective: Social distancing to limit COVID-19 transmission has led to extensive lifestyle changes, including for people with dementia (PWD). The aim of this study, therefore, was to assess the impact of lockdown on the mental health of PWD and their carers.

Methods: Forty-five carers of PWD completed a telephone interview during the baseline assessment of the SOLITUDE study to gather information on life conditions and changes in symptoms of PWD during lockdown.

Altered Interplay Among Large-Scale Brain Functional Networks Modulates Multi-Domain Anosognosia in Early Alzheimer's Disease.

Decline in self-awareness is a prevalent symptom in Alzheimer's disease (AD). Current data suggest that an early breakdown in the brain's default mode network (DMN) is closely associated with the main symptomatic features in AD patients. In parallel, the integrity of the DMN has been shown to be heavily implicated in retained self-awareness abilities in healthy individuals and AD patients.

Serial Recall Order of Category Fluency Words: Exploring Its Neural Underpinnings.

Although performance on the category fluency test (CFT) is influenced by many cognitive functions (i.e., including language, executive functioning and speed of processing), item-level scoring methods of CFT performance might be a promising way to capture aspects of semantic memory that are less influenced by intervenient abilities.

Large-Scale Functional Networks, Cognition and Brain Structures Supporting Social Cognition and Theory of Mind Performance in Prodromal to Mild Alzheimer's Disease.

Impairment of social cognition (SC) skills such as recognition and attribution of intentions and affective states of others (Theory of Mind, ToM) has been evidenced in Alzheimer's Disease (AD). This study investigated the neuropsychological, neuroanatomical and brain-functional underpinnings of SC processing to obtain an understanding of the social neurophenotype in early probable AD. Forty-six patients with mild cognitive impairment and mild probable AD underwent SC assessment including emotion recognition (Ekman-60-faces task) and cognitive and affective ToM (Reading-the-Mind-in-the-Eyes test and Story-based Empathy task).

White-Matter Hyperintensity Load and Differences in Resting-State Network Connectivity Based on Mild Cognitive Impairment Subtype.

"Mild cognitive impairment" (MCI) is a diagnosis characterised by deficits in episodic memory (aMCI) or in other non-memory domains (naMCI). Although the definition of subtypes is helpful in clinical classification, it provides little insight on the variability of neurofunctional mechanisms (i.e.

Serial Recall Order and Semantic Features of Category Fluency Words to Study Semantic Memory in Normal Ageing.

Category Fluency Test (CFT) is a common measure of semantic memory (SM). Test performance, however, is also influenced by other cognitive functions. We here propose a scoring procedure that quantifies the correlation between the serial recall order (SRO) of words retrieved during the CFT and a number of linguistic features, to obtain purer SM measures.

Characterising Alzheimer's Disease With EEG-Based Energy Landscape Analysis.

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases, with around 50 million patients worldwide. Accessible and non-invasive methods of diagnosing and characterising AD are therefore urgently required. Electroencephalography (EEG) fulfils these criteria and is often used when studying AD.