APOE ε4 and Insulin Resistance Influence Path-Integration-Based Navigation through Distinct Large-Scale Network Mechanisms.

Path integration (PI), which supports navigation without external spatial cues, is facilitated by grid cells in the entorhinal cortex. These cells are often impaired in individuals at risk for Alzheimer's disease (AD). However, other brain systems can compensate for this impairment, especially when spatial cues are available.

Alterations in Gray Matter Structural Networks in Amnestic Mild Cognitive Impairment: A Source-Based Morphometry Study.

Background: Amnestic mild cognitive impairment (aMCI), considered as the prodromal stage of Alzheimer's disease, is characterized by isolated memory impairment and cerebral gray matter volume (GMV) alterations. Previous structural MRI studies in aMCI have been mainly based on univariate statistics using voxel-based morphometry.

Objective: We investigated structural network differences between aMCI patients and cognitively normal older adults by using source-based morphometry, a multivariate approach that considers the relationship between voxels of various parts of the brain.

The shift in the fatty acid composition of the circulating lipidome in Alzheimer's disease.

Introduction: Fatty acids (FAs) are the building blocks of complex lipids and signaling compounds; the role of the lipidome fatty acid profile (LFA) in AD progression remains unclear.

Methods: The LFA of plasma and cerebrospinal fluid (CSF) samples from 289 participants (103 AD patients, 92 MCI patients, and 94 controls) was determined by GC-FID. The MCI subjects were followed up for 58 ± 12.

Plasma and cerebrospinal fluid nonenzymatic protein damage is sustained in Alzheimer's disease.

Background: Oxidative stress is considered to play an important role in the pathogenesis of Alzheimer's disease (AD). It has been observed that oxidative damage to specific protein targets affecting particular functional networks is one of the mechanisms by which oxidative stress contributes to neuronal failure and consequently loss of cognition and AD progression. Studies are lacking in which oxidative damage is measured at both systemic and central fluid levels and in the same cohort of patients.

Cortical amyloid-beta burden is associated with changes in intracortical myelin in cognitively normal older adults.

Amyloid-beta (Aβ) aggregates and myelin breakdown are among the earliest detrimental effects of Alzheimer's disease (AD), likely inducing abnormal patterns of neuronal communication within cortical networks. However, human in vivo evidence linking Aβ burden, intracortical myelin, and cortical synchronization is lacking in cognitively normal older individuals. Here, we addressed this question combining F-Florbetaben-PET imaging, cortical T1-weigthed/T2-weighted (T1w/T2w) ratio maps, and resting-state functional connectivity (rs-FC) in cognitively unimpaired older adults.

Effects of non-modifiable risk factors of Alzheimer's disease on intracortical myelin content.

Background: Non-modifiable risk factors of Alzheimer's disease (AD) have lifelong effects on cortical integrity that could be mitigated if identified at early stages. However, it remains unknown whether cortical microstructure is affected in older individuals with non-modifiable AD risk factors and whether altered cortical tissue integrity produces abnormalities in brain functional networks in this AD-risk population.

Methods: Using relative T1w/T2w (rT1w/T2w) ratio maps, we have compared tissue integrity of normal-appearing cortical GM between controls and cognitively normal older adults with either APOE4 (N = 50), with a first-degree family history (FH) of AD (N = 52), or with the co-occurrence of both AD risk factors (APOE4+FH) (N = 35).

Pre-diabetes is associated with altered functional connectivity density in cortical regions of the default-mode network.

Insulin resistance and glucose dysregulation are associated with patterns of regional brain hypometabolism characteristic of Alzheimer's disease (AD). As predicted by evidence linking brain glucose metabolism to brain functional connectivity, type 2 diabetes is accompanied by altered functional connectivity density (FCD) in regions highly vulnerable to AD, but whether these alterations start at earlier stages such as pre-diabetes remain to be elucidated. Here, in addition to assessing whether pre-diabetes leads to a functional reorganization of densely connected cortical areas (hubs), we will assess whether such reorganization is conditioned by sex and/or insulin resistance, and contributes to improved cognition.

Linking Plasma Amyloid Beta and Neurofilament Light Chain to Intracortical Myelin Content in Cognitively Normal Older Adults.

Evidence suggests that lightly myelinated cortical regions are vulnerable to aging and Alzheimer's disease (AD). However, it remains unknown whether plasma markers of amyloid and neurodegeneration are related to deficits in intracortical myelin content, and whether this relationship, in turn, is associated with altered patterns of resting-state functional connectivity (rs-FC). To shed light into these questions, plasma levels of amyloid-β fragment 1-42 (Aβ) and neurofilament light chain (NfL) were measured using ultra-sensitive single-molecule array (Simoa) assays, and the intracortical myelin content was estimated with the ratio T1-weigthed/T2-weighted (T1w/T2w) in 133 cognitively normal older adults.

Lactoferrin as Immune-Enhancement Strategy for SARS-CoV-2 Infection in Alzheimer's Disease Patients.

Coronavirus 2 (SARS-CoV2) (COVID-19) causes severe acute respiratory syndrome. Severe illness of COVID-19 largely occurs in older people and recent evidence indicates that demented patients have higher risk for COVID-19. Additionally, COVID-19 further enhances the vulnerability of older adults with cognitive damage.

JNK1 and JNK3: divergent functions in hippocampal metabolic-cognitive function.

Background And Aim: The appearance of alterations in normal metabolic activity has been increasingly considered a risk factor for the development of sporadic and late-onset neurodegenerative diseases. In this report, we induced chronic metabolic stress by feeding of a high-fat diet (HFD) in order to study its consequences in cognition. We also studied the effects of a loss of function of isoforms 1 and 3 of the c-Jun N-terminal Kinases (JNK), stress and cell death response elements.

Stability of neural encoding moderates the contribution of sleep and repeated testing to memory consolidation.

There is evidence suggesting that online consolidation during retrieval-mediated learning interacts with offline consolidation during subsequent sleep to transform memory. Here we investigate whether this interaction persists when retrieval-mediated learning follows post-training sleep and whether the direction of this interaction is conditioned by the quality of encoding resulting from manipulation of the amount of sleep on the previous night. The quality of encoding was determined by computing the degree of similarity between EEG-activity patterns across restudy of face pairs in two groups of young participants, one who slept the last 4 h of the pre-training night, and another who slept 8 h.

Salivary lactoferrin is associated with cortical amyloid-beta load, cortical integrity, and memory in aging.

Background: Aging is associated with declining protective immunity and persistent low-grade inflammatory responses, which significantly contribute to Alzheimer's disease (AD) pathogenesis. Detecting aging-related cerebral vulnerability associated with deterioration of the immune system requires from non-invasive biomarkers able to detect failures in the brain-immunity connection. Reduced levels of salivary lactoferrin (sLF), an iron-binding protein with immunomodulatory activity, have been related to AD diagnosis.

Cancer survivors referred to a long-term survivorship outpatient service within academic medical oncology: descriptive study.

Purpose: Long-term cancer survivors (LTCS) are a vulnerable and continued growing population. To date, only few studies have been conducted in the Spanish population; none of them with a comprehensive analysis of the most common problems identified for cancer survivors in order to improve their care and quality of life.

Methods: We conducted an observational descriptive study in 347 patients recruited between January 2015 and December 2016 from our newly created medical office for the specific care and follow-up of LTCS.

Plasma tau predicts cerebral vulnerability in aging.

Identifying cerebral vulnerability in late life may help prevent or slow the progression of aging-related chronic diseases. However, non-invasive biomarkers aimed at detecting subclinical cerebral changes in the elderly are lacking. Here, we have examined the potential of plasma total tau (t-tau) for identifying cerebral and cognitive deficits in normal elderly subjects.

Unmasking selective path integration deficits in Alzheimer's disease risk carriers.

Alzheimer's disease (AD) manifests with progressive memory loss and spatial disorientation. Neuropathological studies suggest early AD pathology in the entorhinal cortex (EC) of young adults at genetic risk for AD ( ε4-carriers). Because the EC harbors grid cells, a likely neural substrate of path integration (PI), we examined PI performance in ε4-carriers during a virtual navigation task.

Decreased salivary lactoferrin levels are specific to Alzheimer's disease.

Background: Evidences of infectious pathogens in Alzheimer's disease (AD) brains may suggest a deteriorated innate immune system in AD pathophysiology. We previously demonstrated reduced salivary lactoferrin (Lf) levels, one of the major antimicrobial proteins, in AD patients.

Methods: To assess the clinical utility of salivary Lf for AD diagnosis, we examine the relationship between salivary Lf and cerebral amyloid-β (Aβ) load using amyloid-Positron-Emission Tomography (PET) neuroimaging, in two different cross-sectional cohorts including patients with different neurodegenerative disorders.

Blood total antioxidant status is associated with cortical glucose uptake and factors related to accelerated aging.

Identifying cerebral vulnerability in late life is of paramount importance to prevent pathological trajectories of aging before the onset of symptoms. Considerable evidence suggests that impaired antioxidant mechanisms are a fingerprint of aging-related conditions, but there is a lack of human research linking total antioxidant capacity (TAC) measured in peripheral blood to in vivo brain changes and other factors featuring accelerated aging. To address this issue, we have assessed in cognitively normal elderly subjects (N = 100) correlations between serum TAC, using the oxygen radical absorbance capacity assay, surface-based cortical thickness, surface-based 18F-fluorodeoxyglucose positron emission tomography cortical uptake, and different factors associated with accelerated aging [i.

Weakly encoded memories due to acute sleep restriction can be rescued after one night of recovery sleep.

Sleep is thought to play a complementary role in human memory processing: sleep loss impairs the formation of new memories during the following awake period and, conversely, normal sleep promotes the strengthening of the already encoded memories. However, whether sleep can strengthen deteriorated memories caused by insufficient sleep remains unknown. Here, we showed that sleep restriction in a group of participants caused a reduction in the stability of EEG activity patterns across multiple encoding of the same event during awake, compared with a group of participants that got a full night's sleep.