Change in Depressive Symptoms and Longitudinal Regional Amyloid Accumulation in Unimpaired Older Adults.

Importance: Depressive symptoms in older adults may be a harbinger of Alzheimer disease (AD), even in preclinical stages. It is unclear whether worsening depressive symptoms are manifestations of regional distributions of core AD pathology (amyloid) and whether cognitive changes affect this relationship.

Objective: To evaluate whether increasing depressive symptoms are associated with amyloid accumulation in brain regions important for emotional regulation and whether those associations vary by cognitive performance.

Amyloid and tau burden relate to longitudinal changes in the performance of complex everyday activities among cognitively unimpaired older adults: results from the performance-based Harvard Automated Phone Task.

Background: Changes in everyday functioning constitute a clinically meaningful outcome, even in the early stages of Alzheimer's disease. Performance-based assessments of everyday functioning might help uncover these early changes. We aimed to investigate how changes over time in everyday functioning relate to tau and amyloid in cognitively unimpaired older adults.

Multi-modal Neuroimaging Phenotyping of Mnemonic Anosognosia in the Aging Brain.

Background: Unawareness is a behavioral condition characterized by a lack of self-awareness of objective memory decline. In the context of Alzheimer's Disease (AD), unawareness may develop in predementia stages and contributes to disease severity and progression. Here, we use in-vivo multi-modal neuroimaging to profile the brain phenotype of individuals presenting altered self-awareness of memory during aging.

Anosognosia is associated with increased prevalence and faster development of neuropsychiatric symptoms in mild cognitive impairment.

Introduction: Both the loss of awareness for cognitive decline (a. k.a anosognosia) and neuropsychiatric symptoms (NPS) are common in patients with Alzheimer's disease (AD) dementia, even in prodromal stages, and may exacerbate functional impairment and negatively impact caregiver burden.

Study Partner Report of Apathy in Older Adults is Associated with AD Biomarkers: Findings from the Harvard Aging Brain Study.

Objectives: We examined relationships between apathy (self and study-partner-reported) and markers of Alzheimer's disease (AD) in older adults.

Design: The study utilized a well-characterized sample of participants from the Harvard Aging Brain Study (HABS), a longitudinal cohort study. Participants were cognitively unimpaired without clinically significant neuropsychiatric symptoms at HABS baseline.

Association of Pathologic and Volumetric Biomarker Changes With Cognitive Decline in Clinically Normal Adults.

Background And Objectives: Hippocampal volume (HV) atrophy is a well-known biomarker of memory impairment. However, compared with β-amyloid (Aβ) and tau imaging, it is less specific for Alzheimer disease (AD) pathology. This lack of specificity could provide indirect information about potential copathologies that cannot be observed in vivo.

Recent contributions to the field of subjective cognitive decline in aging: A literature review.

Subjective cognitive decline (SCD) is defined as self-experienced, persistent concerns of decline in cognitive capacity in the context of normal performance on objective cognitive measures. Although SCD was initially thought to represent the "worried well," these concerns can be linked to subtle brain changes prior to changes in objective cognitive performance and, therefore, in some individuals, SCD may represent the early stages of an underlying neurodegenerative disease process (e.g.

Depressive symptoms and hippocampal volume in autosomal dominant Alzheimer's disease.

Introduction: Depressive symptoms are among early behavioral changes in Alzheimer's disease (AD); however, the relationship between neurodegeneration and depressive symptoms remains inconclusive. To better understand this relationship in preclinical AD, we examined hippocampal volume and depressive symptoms in cognitively unimpaired carriers of the presenilin-1 (PSEN1) E280A mutation for autosomal dominant AD.

Methods: A total of 27 PSEN1 mutation carriers and 26 non-carrier family members were included.

Cortical microstructural changes predict tau accumulation and episodic memory decline in older adults harboring amyloid.

Introduction: Non-invasive diffusion-weighted imaging (DWI) to assess brain microstructural changes via cortical mean diffusivity (cMD) has been shown to be cross-sectionally associated with tau in cognitively normal older adults, suggesting that it might be an early marker of neuronal injury. Here, we investigated how regional cortical microstructural changes measured by cMD are related to the longitudinal accumulation of regional tau as well as to episodic memory decline in cognitively normal individuals harboring amyloid pathology.

Methods: 122 cognitively normal participants from the Harvard Aging Brain Study underwent DWI, T1w-MRI, amyloid and tau PET imaging, and Logical Memory Delayed Recall (LMDR) assessments.

Regional cerebral tau predicts decline in everyday functioning across the Alzheimer's disease spectrum.

Background: Emerging difficulty performing cognitively complex everyday tasks, or 'instrumental activities of daily living' (IADL) may be an early clinical sign of Alzheimer's disease (AD). We aimed to investigate how changes over time in everyday functioning relate to cerebral tau burden across the AD clinical spectrum.

Methods: We included 581 participants (73.

Associations of the Harvard Automated Phone Task and Alzheimer's Disease Pathology in Cognitively Normal Older Adults: Preliminary Findings.

Background: Detecting clinically meaningful changes in instrumental activities of daily living (IADL) at the earliest stages of Alzheimer's disease (AD) is critical.

Objective: The objective of this exploratory study was to examine the cross-sectional relationship between a performance-based IADL test, the Harvard Automated Phone Task (APT), and cerebral tau and amyloid burden in cognitively normal (CN) older adults.

Methods: Seventy-seven CN participants underwent flortaucipir tau and Pittsburgh Compound B amyloid PET.

Measurement of Dimensions of Self-awareness of Memory Function and Their Association With Clinical Progression in Cognitively Normal Older Adults.

Importance: The ability to separately explore 2 dimensions of self-awareness of memory function-increased and decreased awareness-in cognitively normal older adults provides an important opportunity to understand subtle changes in either direction in relation to risk of Alzheimer disease.

Objective: To investigate the association of a novel measure for self-awareness of memory function with future clinical progression in individuals who were cognitively normal at baseline.

Design, Setting, And Participants: This cohort study used data from the Alzheimer's Disease Neuroimaging Initiative, a multicenter study.

Network Tau spreading is vulnerable to the expression gradients of and glutamatergic-related genes.

A key hallmark of Alzheimer's disease (AD) pathology is the intracellular accumulation of tau protein in the form of neurofibrillary tangles across large-scale networks of the human brain cortex. Currently, it is still unclear how tau accumulates within specific cortical systems and whether in situ genetic traits play a role in this circuit-based propagation progression. In this study, using two independent cohorts of cognitively normal older participants, we reveal the brain network foundation of tau spreading and its association with using high-resolution transcriptomic genetic data.

Association of Emerging β-Amyloid and Tau Pathology With Early Cognitive Changes in Clinically Normal Older Adults.

Background And Objectives: Alzheimer disease (AD) clinical trials are moving earlier in the disease process according to emerging signs of β-amyloid (Aβ) and tau pathology. If early treatment is the right time for intervention, it is critical to find the right test to optimize cognitive outcome measures for clinical trials. We sought to identify cognitive measures associated with the earliest detectable signs of emerging Aβ and tau pathology.

Racial and socioeconomic status differences in stress, posttraumatic growth, and mental health in an older adult cohort during the COVID-19 pandemic.

Background: The COVID-19 pandemic has disproportionately impacted the most vulnerable and widened the health disparity gap in both physical and mental well-being. Consequentially, it is vital to understand how to best support elderly individuals, particularly Black Americans and people of low socioeconomic status, in navigating stressful situations during the COVID-19 pandemic and beyond. The aim of this study was to investigate perceived levels of stress, posttraumatic growth, coping strategies, socioeconomic status, and mental health between Black and non-Hispanic, White older adults, the majority over the age of 70.

Longitudinal Trajectories of Participant- and Study Partner-Rated Cognitive Decline, in Relation to Alzheimer's Disease Biomarkers and Mood Symptoms.

Whereas discrepancies between participant- and study partner-reported cognitive concerns on the Alzheimer's disease (AD) continuum have been observed, more needs to be known regarding the longitudinal trajectories of participant- vs. study partner-reported concerns, particularly their relationship to AD biomarkers and mood symptomology. Additionally, it is unclear whether years of in-clinic data collection are needed to observe relationships with AD biomarkers, or whether more frequent, remote assessments over shorter periods of time would suffice.

Episodic Memory Impairment Mediates the Loss of Awareness in Mild Cognitive Impairment.

Introduction: Loss of awareness is a common symptom in Alzheimer's Disease (AD) and responsible for a significant loss of functional abilities. The mechanisms underlying loss of awareness in AD is unknown, although previous findings have implicated dysfunction of primary executive functioning (EF) or episodic memory (EM) to be the cause. Therefore, our main study objective was to explore the involvement of EF and EM dysfunction in amyloid-related loss of awareness across the clinical spectrum of AD.

Association of cortical microstructure with amyloid-β and tau: impact on cognitive decline, neurodegeneration, and clinical progression in older adults.

Noninvasive biomarkers of early neuronal injury may help identify cognitively normal individuals at risk of developing Alzheimer's disease (AD). A recent diffusion-weighted imaging (DWI) method allows assessing cortical microstructure via cortical mean diffusivity (cMD), suggested to be more sensitive than macrostructural neurodegeneration. Here, we aimed to investigate the association of cMD with amyloid-β and tau pathology in older adults, and whether cMD predicts longitudinal cognitive decline, neurodegeneration and clinical progression.

Awareness of Cognitive Decline in Patients With Alzheimer's Disease: A Systematic Review and Meta-Analysis.

Identifying a poor degree of awareness of cognitive decline (ACD) could represent an early indicator of Alzheimer's disease (AD). (1) to understand whether there is evidence of poor ACD in the pre-dementia stages of AD; (2) to summarize the main findings obtained investigating ACD in AD; (3) to propose a conceptual framework. We searched Scopus, Pubmed, and the reference lists for studies published up to August 2020.

Cortical Networks of Creative Ability Trace Gene Expression Profiles of Synaptic Plasticity in the Human Brain.

The ability to produce novel ideas is central to societal progress and innovation; however, little is known about the biological basis of creativity. Here, we investigate the organization of brain networks that support creativity by combining functional neuroimaging data with gene expression information. Given the multifaceted nature of creative thinking, we hypothesized that distributed connectivity would not only be related to individual differences in creative ability, but also delineate the cortical distributions of genes involved in synaptic plasticity.