Basic Science and Pathogenesis.

Background: Previously, we identified macropinocytosis as a novel mechanism for direct and rapid trafficking of cell surface APP to lysosomes, bypassing early and late endosomes. This process depends on the activity of Arf6 and several Rho-GTPases, and inhibition of macropinocytosis reduces amyloid-beta (Aβ) production. Macropinocytosis is relatively unstudied in neurons and neuronal cells.

Basic Science and Pathogenesis.

Background: Alzheimer's disease (AD) is characterized by the accumulation of amyloid-β (Aβ) plaques and tau tangles in the brain, and neurotransmission dysfunctions. Indeed, our group recently demonstrated that the γ-aminobutyric acid (GABA)ergic system is vulnerable to AD pathology in humans. However, whether this vulnerability is also present in AD rodent models is still unknown.

Basic Science and Pathogenesis.

Background: Murine models of Alzheimer's Disease (AD) have resulted in numerous discoveries leading to a better understanding of AD pathogenesis but results poorly translated to novel treatment options. Over the past years, iPSC-derived human neuronal cultures have been developed to better model AD in vitro. One key hallmark of AD is the presence of insoluble Aß plaques in the brain.

Basic Science and Pathogenesis.

Background: The endocannabinoid system has demonstrated roles in Alzheimer's Disease (AD), such as modulation of inflammation. Fatty Acid Amide Hydrolase (FAAH) is the enzyme responsible for the rapid inactivation of the endocannabinoid anandamide into arachidonic acid and ethanolamine. In doing so, FAAH modulates the concentration of anandamide and influences neurobehavioral functions and physiological conditions such as nociception and inflammatory responses.

Basic Science and Pathogenesis.

Background: Altered lipid profiles and lipid processing genes are associated with Alzheimer's disease (AD). There is a reported genetic interaction between the AD risk gene APOE and cholesterol ester transfer protein (CETP). Mice lack functional CETP which is critical to the balance of circulating lipoproteins; this imparts cardioprotective effects and may make mice resistant to AD.

Clinical Manifestations.

Background: Mild Behavioral Impairment (MBI) and functional ability are two non-cognitive markers of dementia. To date, little is known about the impact of functional ability on the clinical manifestation of MBI. Using data from the Australian population-based PATH Through Life Study we examined the impact of functional ability on MBI.

Clinical Manifestations.

Background: Despite the clinical importance and significant social burden of neuropsychiatric symptoms (NPS) in dementia, the underlying neurobiological mechanism remains poorly understood. Recently, neuroimaging-derived brain-age estimation by machine-learning analysis has shown promise as an individual-level biomarker. We investigated the relationship between NPS and brain-age in amnestic mild cognitive impairment (MCI) and early dementia.

Clinical Manifestations.

Background: Globally, females are at twice the risk of AD than males; in Canada, over 700,000 are living with Alzheimer's disease and related dementia (ADRDs), with 72% being female. However, females maintain verbal memory in the face of more AD pathology than men. It is unclear how multilingualism, considered a resilience factor, might interact with the risk and resilience of sex.

Clinical Manifestations.

Background: Multispecialty Interprofessional Team (MINT) Memory Clinics manage dementia care in primary care, allowing for more efficient use of limited specialist resources. This study examined the characteristics of patients on their initial assessment in the MINT clinic and investigated the five-year trajectory of patients with mild cognitive impairment (MCI).

Method: We conducted a retrospective chart review of 751 patients assessed within a MINT Memory Clinic between June 2006 and May 2019 to collect data on age, gender, diagnosis, and MoCA scores.

Clinical Manifestations.

Background: Subjective cognitive decline (SCD), or self-perceived declines in memory/cognition in cognitively healthy older adults is linked to increased cognitive decline, neurodegeneration, and white matter hyperintensity (WMH) burden. However, there is no consistent definition of how to classify people with SCD. This study investigated if individual questions in the Cognitive Change Index (CCI) and Everyday Cognition Scale (ECog), commonly used to classify SCD, are associated with brain volume and WMHs to the same degree.

Clinical Manifestations.

Background: Changes in the structure and use of language are well established clinical characteristics of Alzheimer's disease. In recent years, there has been a concerted effort to objectively quantify these changes using the latest advances in Natural Language Processing (NLP) tools. Much academic research has been conducted to evaluate how these speech characteristics change with the course of illness, but they have yet to be elevated beyond exploratory endpoints in trials.

Clinical Manifestations.

Background: Patients with Primary Progressive Aphasias (PPAs) almost systematically inquire about the longitudinal evolution of their disease in clinics but very little research exists on the issue.

Method: We studied 82 PPA patients from the Research Chair on PPA - Fondation de la Famille Lemaire Cohort over a 10-year span (42 logopenic, 21 non-fluent/agrammatic and 19 semantic PPAs) and collected data from 5 domains (language, cognition, motor, psychiatric, functional) at 5 time points from onset to death. Logistical regression analyses and repeated measures ANOVAs were conducted to delineate the longitudinal profile of each variant PPA.

Clinical Manifestations.

Background: Frontotemporal degeneration (FTD) is a complex, heterogeneous group of fatal adult-onset disorders which lead to progressive dysfunction in behavior, motor symptoms, language, and/or cognition. While advances in research are cause for optimism, trials are hindered by the availability of participants. As FTD clinical trials typically require co-participation of a study partner, care partner perspectives on research are critical to understanding how to support recruitment and retention.

Basic Science and Pathogenesis.

Background: Parkinson's disease and dementia with Lewy bodies are more common in men, while Alzheimer's disease (AD) is more common in women. Lewy body disease (LBD) and AD pathologies are highly comorbid and may be mechanistically linked. It remains unclear whether LBD and AD co-pathology manifest differently across sexes.

The impact of n-3 polyunsaturated fatty acids in patients with cancer: emerging themes.

Purpose Of Review: This review summarizes recent literature falling broadly under the topic of n-3 polyunsaturated fatty acids (PUFAs) in the oncology setting, highlighting emerging themes and emphasizing novel explorations.

Recent Findings: Meta-analyses continue to confirm safety and efficacy of n-3 PUFA supplementation on reducing inflammation and improving survival in people with cancer. Common themes in recent studies emphasize improving tumor-directed efficacy and reducing toxicities of common cancer therapies.

Clinical Manifestations.

Background: Previous literature has highlighted that excessive alcohol use (EAU) is directly linked with permanent neurological damage. Studies have also highlighted gradual improvements in heart rate variability (HRV) after cessation of alcohol use. Moreover, chronic alcohol consumption has also been correlated with reduced HRV and an increase in skin conductance (SC) among healthy adults, leading to a combined decline in cognitive performance.

Clinical Manifestations.

Background: Frontotemporal dementia (FTD) presents with heterogeneous neuropsychiatric symptoms (NPS). These symptoms often begin prior to the onset of FTD, and progress throughout the prodromal stages of FTD. Particularly, familial FTD due to autosomal dominant genetic mutations might display mutation-specific NPS profiles.

Clinical Manifestations.

Background: The Montreal Cognitive Assessment (MoCA) stands as a prominent cognitive impairment screening tool, finding widespread use globally and existing in official versions across 14 languages, including Spanish. Despite this, the challenges emerge due to the extensive variations within the Spanish language, which is not only the fourth most spoken language worldwide but also possesses significant geographic diversity, particularly evident in regions like Peru. Here, the intersection of regional nuances, low educational backgrounds, and culturally distinct tasks complicates the application of a standard MoCA version.

Clinical Manifestations.

Background: The Clinical Dementia Rating Sum of Boxes (CDR-SB) is a widely used measurement score to stage dementia severity; it has become one of the most common outcome measurements in Alzheimer's Disease (AD) research. The CDR-SB requires an informant to provide information to stage a patient's dementia severity. The effect of the informant's characteristics including sex and relationship with patients on the CDR-SB is unknown.

Clinical Manifestations.

Background: Depression affects individuals across various ages but is of significance in the older surgical population due to its adverse impact on cognitive function, surgical recovery, and overall functional disability. This study aimed to determine the overall prevalence and trajectory of depression in older surgical patients preoperatively, and at 30-, 90- and 180-days postoperatively.

Method: This study is a prespecified sub-study and analysis of the Postoperative Functional Disability in Unrecognized Cognitive Impairment Study.

Clinical Manifestations.

Background: Apathy may appear as a less acute late-life syndrome; however, it is associated with accelerated progression to dementia and contributes to adverse outcomes for patients and caregivers. These findings are not surprising since apathy can cause individuals to forego activities that improve cardiovascular and cognitive health (e.g.

Clinical Manifestations.

Background: Mild behavioral impairment (MBI) is a syndrome that leverages neuropsychiatric symptoms that emerge in later-life, and which persist, to identify individuals at high-risk for incident dementia. Attendant with MBI are changes in quality of life (QoL), which can present concurrent with the onset of cognitive decline or even before. Obtaining information from participants and study partners can provide a broader overview of health and QoL.

Clinical Manifestations.

Background: Recent research has highlighted the importance of sleep on cognitive processes. However, conflicting evidence exists regarding optimal sleep duration and the impact of other co-occurring conditions, such as depression. A diagnosis of depression in mid-life may increase the risk of developing dementia.

Clinical Manifestations.

Background: Cognitive assessments are essential for the diagnosis of mild cognitive impairment (MCI) and dementia. However, existing tests are mostly developed in English-speaking cohorts. Hence, their application in multilingual populations will need translation which may affect their test psychometrics.

Clinical Manifestations.

Background: Automated analysis of natural speech is emerging as a promising digital biomarker of Alzheimer's disease (AD). As speech is a complex process, relying on multiple interacting cognitive functions, fine-grained analysis of speech may have the potential to capture subtle cognitive deficits in the very early stages of AD. Here, we examined the association between amyloid-beta (Aβ) pathology and acoustic speech characteristics in a group of cognitively normal Dutch adults.