Issues and recommendations for the residual approach to quantifying cognitive resilience and reserve.

Background: Cognitive reserve and resilience are terms used to explain interindividual variability in maintenance of cognitive health in response to adverse factors, such as brain pathology in the context of aging or neurodegenerative disorders. There is substantial interest in identifying tractable substrates of resilience to potentially leverage this phenomenon into intervention strategies. One way of operationalizing cognitive resilience that has gained popularity is the residual method: regressing cognition on an adverse factor and using the residual as a measure of resilience.

Does Loss of Integrity of the Cingulum Bundle Link Amyloid-β Accumulation and Neurodegeneration in Alzheimer's Disease?

Background: Alzheimer's disease is characterized by the accumulation of amyloid-β (Aβ) into plaques, aggregation of tau into neurofibrillary tangles, and neurodegenerative processes including atrophy. However, there is a poorly understood spatial discordance between initial Aβ deposition and local neurodegeneration.

Objective: Here, we test the hypothesis that the cingulum bundle links Aβ deposition in the cingulate cortex to medial temporal lobe (MTL) atrophy.

Clinically Relevant Changes for Cognitive Outcomes in Preclinical and Prodromal Cognitive Stages: Implications for Clinical Alzheimer Trials.

Background And Objectives: Identifying a clinically meaningful change in cognitive test score is essential when using cognition as an outcome in clinical trials. This is especially relevant because clinical trials increasingly feature novel composites of cognitive tests. Our primary objective was to establish minimal clinically important differences (MCIDs) for commonly used cognitive tests, using anchor-based and distribution-based methods, and our secondary objective was to investigate a composite cognitive measure that best predicts a minimal change in the Clinical Dementia Rating-Sum of Boxes (CDR-SB).

The recognition and management of neuropsychiatric symptoms in early Alzheimer's disease: a qualitative study among Dutch memory clinic physicians.

Background: Timely recognition and treatment of neuropsychiatric symptoms (NPS) in Alzheimer's disease (AD) dementia may improve quality of life, reduce caregiver burden, and delay disease progression. However, management of NPS in early AD dementia remains challenging. To date, little is known about the specific challenges for memory clinic-based physicians.

Conditions for uptake of evidence-based knowledge in municipal care for older people in Sweden: a developmental evaluation.

Objective: The objective of this paper is to describe the initial phase of a long-term collaboration initiative between a municipality and the Faculty of Medicine at a university in Sweden. The overall ambition of the collaboration is to strengthen the quality of care for older people. The concrete goal is to equip academically trained registered health care professionals (HCP) with tools for transferring evidence-based knowledge into practice.

Performance of αSynuclein RT-QuIC in relation to neuropathological staging of Lewy body disease.

Currently, there is a need for diagnostic markers in Lewy body disorders (LBD). α-synuclein (αSyn) RT-QuIC has emerged as a promising assay to detect misfolded αSyn in clinically or neuropathologically established patients with various synucleinopathies. In this study, αSyn RT-QuIC was used to analyze lumbar CSF in a clinical cohort from the Swedish BioFINDER study and postmortem ventricular CSF in a neuropathological cohort from the Arizona Study of Aging and Neurodegenerative Disorders/Brain and Body Donation Program (AZSAND/BBDP).

Do genetic factors contribute to sex-specific differences in resilience to amyloid pathology?

This scientific commentary refers to ‘Sex differences in the genetic architecture of cognitive resilience to Alzheimer’s disease’ by Eissman (https://doi.org/10.1093/brain/awac177).

Feasibility of Digital Memory Assessments in an Unsupervised and Remote Study Setting.

Sensitive and frequent digital remote memory assessments via mobile devices hold the promise to facilitate the detection of cognitive impairment and decline. However, in order to be successful at scale, cognitive tests need to be applicable in unsupervised settings and confounding factors need to be understood. This study explored the feasibility of completely unsupervised digital cognitive assessments using three novel memory tasks in a Citizen Science project across Germany.

Biweekly fluctuations of neuropsychiatric symptoms according to the Neuropsychiatric Inventory: Erratic symptoms or scores?

Objectives: This study investigates the stability of neuropsychiatric symptoms (NPS) assessed biweekly using the Neuropsychiatric Inventory (NPI) in a memory clinic population during a 6 week period.

Methods: Twenty-three spousal caregivers (mean [SD] age = 69.7 [8.

Astrocytic function is associated with both amyloid-β and tau pathology in non-demented carriers.

A growing body of evidence suggests that astrocytes play a major role in the pathophysiology of Alzheimer's disease. Given that is primarily expressed in astrocytes, these cells might be an important link between the ε4 allele and the development of Alzheimer's disease pathology. Here, we investigate this hypothesis by measuring myo-inositol, a metabolite involved in astrocytic functions, with magnetic resonance spectroscopy.

Test-retest variability of plasma biomarkers in Alzheimer's disease and its effects on clinical prediction models.

Introduction: The effect of random error on the performance of blood-based biomarkers for Alzheimer's disease (AD) must be determined before clinical implementation.

Methods: We measured test-retest variability of plasma amyloid beta (Aβ)42/Aβ40, neurofilament light (NfL), glial fibrillary acidic protein (GFAP), and phosphorylated tau (p-tau)217 and simulated effects of this variability on biomarker performance when predicting either cerebrospinal fluid (CSF) Aβ status or conversion to AD dementia in 399 non-demented participants with cognitive symptoms.

Results: Clinical performance was highest when combining all biomarkers.

Disease Progression in Multiple System Atrophy-Novel Modeling Framework and Predictive Factors.

Background: Multiple system atrophy (MSA) is a rare and aggressive neurodegenerative disease that typically leads to death 6 to 10 years after symptom onset. The rapid evolution renders it crucial to understand the general disease progression and factors affecting the disease course.

Objectives: The aims of this study were to develop a novel disease-progression model to estimate a population-level MSA progression trajectory and predict patient-specific continuous disease stages describing the degree of progress into the disease.

Tau PET Imaging in Neurodegenerative Disorders.

The advent of PET ligands that bind tau pathology has enabled the quantification and visualization of tau pathology in aging and in Alzheimer disease (AD). There is strong evidence from neuropathologic studies that the most widely used tau PET tracers (i.e.

Tau biomarkers in Alzheimer's disease: towards implementation in clinical practice and trials.

Background: Deposition of tau aggregates is a pathological hallmark of Alzheimer's disease that is closely linked both spatially and temporally to emergence of neurodegeneration and manifestation of clinical symptoms. There is an urgent need for accurate PET, CSF, and plasma biomarkers of tau pathology to improve the diagnostic process in clinical practice and the selection of participants and monitoring of treatment effects in trials.

Recent Developments: Innovative second-generation tau-PET tracers with high affinity and selectivity to tau pathology in Alzheimer's disease have enabled detection of tau pathology in medial temporal lobe subregions that are affected in the earliest disease stages.

β-Amyloid-Dependent and -Independent Genetic Pathways Regulating CSF Tau Biomarkers in Alzheimer Disease.

Background And Objectives: Abnormal metabolism of β-amyloid (Aβ) and soluble phosphorylated tau (P-tau), as well as neurodegeneration, are key components of Alzheimer disease (AD), but it is unclear how these different processes are related to genetic risk factors for AD.

Methods: In the Swedish BioFINDER study, we tested associations between a priori defined polygenic risk scores (PRSs) for AD (excluding single-nucleotide polymorphism [SNP] within the region in the main analysis) and biomarkers in CSF (total tau [T-tau] and P-tau181; Aβ1-38, Aβ1-40, Aβ1-42, and Aβ1-42/1-40; and neurofilament light [NfL]) in cognitively unimpaired (CU) individuals (n = 751), and in patients with mild cognitive impairment (MCI) (n = 212) and AD dementia (n = 150). Results were validated in the Alzheimer's Disease Neuroimaging Initiative data set with 777 individuals (AD = 119, MCI = 442, and CU = 216).

Relationship between cerebrospinal fluid neurodegeneration biomarkers and temporal brain atrophy in cognitively healthy older adults.

It is unclear whether cerebrospinal fluid (CSF) biomarkers of neurodegeneration predict brain atrophy in cognitively healthy older adults, whether these associations can be explained by phosphorylated tau181 (p-tau) and the 42 amino acid form of amyloid-β (Aβ42) biomarkers, and which neural substrates may drive these associations. We addressed these questions in 2 samples of cognitively healthy older adults who underwent longitudinal structural MRI up to 7 years and had baseline CSF levels of heart-type fatty-acid binding protein (FABP3)=, total-tau, neurogranin, and neurofilament light (NFL) (n = 189, scans = 721). The results showed that NFL, total-tau, and FABP3 predicted entorhinal thinning and hippocampal atrophy.

Behavioral and Psychological Symptoms of Dementia in Different Dementia Disorders: A Large-Scale Study of 10,000 Individuals.

Background: The majority of individuals with dementia will suffer from behavioral and psychological symptoms of dementia (BPSD). These symptoms contribute to functional impairment and caregiver burden.

Objective: To characterize BPSD in Alzheimer's disease (AD), vascular dementia (VaD), mixed (Mixed) dementia, Parkinson's disease dementia (PDD), dementia with Lewy bodies (DLB), frontotemporal dementia (FTD), and unspecified dementia in individuals residing in long-term care facilities.

Medications causing potential cognitive impairment are common in nursing home dementia units - A cross-sectional study.

Background: With advancing age the brain becomes more sensitive to centrally acting drugs thus increasing the risk of cognitive side-effects. The Swedish National Board of Health and Welfare developed indicators to measure and follow quality in older people's drug therapy, one being "Potentially Inappropriate Medications risking Cognitive impairment (PIMcogn)". Associations between anticholinergics and cognitive impairment are described, especially in persons with Alzheimer's disease or Lewy Body Dementia/Parkinson's disease dementia, due to degenerated cholinergic pathways.

Reduction in Volume of Nucleus Basalis of Meynert Is Specific to Parkinson's Disease and Progressive Supranuclear Palsy but Not to Multiple System Atrophy.

Objectives: To study gray matter (GM) volumes of the nucleus basalis of Meynert (nbM) in different parkinsonian syndromes and assess their relationship with clinical variables.

Methods: T1-weighted magnetic resonance images from patients with progressive supranuclear palsy (PSP, = 43), multiple system atrophy (MSA, = 23), Parkinson's disease (PD, = 26), and healthy controls (HC, = 29) were included. T1-weighted images were analyzed using a voxel-based morphometry approach implemented in the VBM8 toolbox, and nbM volumes were extracted from the spatially normalized GM images using a cyto-architectonically-defined nbM mask in stereotactic standard space.

Quantification of amyloid PET for future clinical use: a state-of-the-art review.

Amyloid-β (Aβ) pathology is one of the earliest detectable brain changes in Alzheimer's disease (AD) pathogenesis. The overall load and spatial distribution of brain Aβ can be determined in vivo using positron emission tomography (PET), for which three fluorine-18 labelled radiotracers have been approved for clinical use. In clinical practice, trained readers will categorise scans as either Aβ positive or negative, based on visual inspection.

Brain charts for the human lifespan.

Over the past few decades, neuroimaging has become a ubiquitous tool in basic research and clinical studies of the human brain. However, no reference standards currently exist to quantify individual differences in neuroimaging metrics over time, in contrast to growth charts for anthropometric traits such as height and weight. Here we assemble an interactive open resource to benchmark brain morphology derived from any current or future sample of MRI data ( http://www.