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Superior Memory Reduces 8-year Risk of Mild Cognitive Impairment and Dementia But Not Amyloid β-Associated Cognitive Decline in Older Adults.
OBJECTIVE: To prospectively examine 8-year risk of clinical disease progression to mild cognitive impairment (MCI)/dementia in older adults ≥60 with superior episodic memory (SuperAgers) compared to those cognitively normal for their age (CNFA). Additionally, to determine the extent to which SuperAgers were resilient to the negative effects of elevated amyloid-beta (Aβ+) on cognition. METHOD: Participants […]
A Polygenic Risk Score Derived From Episodic Memory Weighted Genetic Variants Is Associated With Cognitive Decline in Preclinical Alzheimer’s Disease.
Studies of Alzheimer’s disease risk-weighted polygenic risk scores (PRSs) for cognitive performance have reported inconsistent associations. This inconsistency is particularly evident when PRSs are assessed independent of APOE genotype. As such, the development and assessment of phenotype-specific weightings to derive PRSs for cognitive decline in preclinical AD is warranted. To this end a episodic memory-weighted […]
Utility of an Alzheimer’s Disease Risk-Weighted Polygenic Risk Score for Predicting Rates of Cognitive Decline in Preclinical Alzheimer’s Disease: A Prospective Longitudinal Study.
BACKGROUND: With the exception of APOE, genetic variants associated with increased Alzheimer’s disease (AD) risk are characterized by small effect sizes. Polygenic risk scores (PRS) have shown utility in predicting AD risk; however, their utility for predicting decline in cognition at preclinical stages of AD is poorly understood. OBJECTIVE: To validate associations of a 22-variant […]
Safety, tolerability and efficacy of the glutaminyl cyclase inhibitor PQ912 in Alzheimer’s disease: results of a randomized, double-blind, placebo-controlled phase 2a study.
BACKGROUND: PQ912 is an inhibitor of the glutaminyl cyclase enzyme that plays a central role in the formation of synaptotoxic pyroglutamate-A-beta oligomers. We report on the first clinical study with PQ912 in subjects with biomarker-proven Alzheimer’s disease (AD). The aim was to determine the maximal tolerated dose, target occupancy and treatment-related pharmacodynamic effects. The exploratory […]
Relationship Between Amyloid-β Positivity and Progression to Mild Cognitive Impairment or Dementia over 8 Years in Cognitively Normal Older Adults.
BACKGROUND: Preclinical Alzheimer’s disease (AD) is defined by cerebral amyloid-β positivity (Aβ+) in cognitively normal (CN) older adults. OBJECTIVE: To estimate the risk of progression to the symptomatic stages of AD due to PET Aβ+ and the extent that progression was influenced by other demographic, genetic, and clinical characteristics in a large prospective study. METHODS: Fine-Gray […]
Episodic Memory and Learning Dysfunction Over an 18-Month Period in Preclinical and Prodromal Alzheimer’s Disease.
Recent meta-analyses suggest that episodic memory impairment associated with preclinical Alzheimer’s disease (AD) equates to 0.15-0.24 standard deviations below that of cognitively healthy older adults. The current study aimed to characterize impairments in verbal acquisition and recall detectable at a single assessment, and investigate how verbal learning and episodic memory deteriorates in preclinical AD. A […]
Analysis of the Relationship of Cognitive Impairment and Functional Impairment in Mild Alzheimer’s Disease in EXPEDITION 3.
BACKGROUND: Clinical progression of Alzheimer’s disease is characterized by impairment in cognition and function. OBJECTIVE: To assess the relationship between cognitive and functional impairment in mild Alzheimer’s disease. DESIGN: Spearman’s rank correlations between cognitive and functional measures were calculated. Autoregressive cross-lagged panel analyses were used to determine the temporal relationship between cognitive and functional decline. […]
Associations of Dietary Protein and Fiber Intake with Brain and Blood Amyloid-β.
Accumulating evidence suggests a diet high in protein and fiber may confer some protection against Alzheimer’s disease (AD). However, no human studies to-date have assessed the relationship between protein and fiber intake, and plasma and brain amyloid-β (Aβ). Consequently, this cross-sectional study, investigated the association of self-reported dietary intakes of protein and fiber, with plasma […]
Lorazepam Challenge for Individuals at Varying Genetic Risk for Alzheimer Disease.
INTRODUCTION: This study set out to clarify the differential acute cognitive impact of lorazepam based on varying genetic risk for Alzheimer disease. METHODS: Fifty-seven cognitively unimpaired individuals aged 51 to 88, genotyped according to apolipoprotein E (APOE) and translocase of outer mitochondrial membrane (40 homolog) poly-T lengths, completed cognitive testing before, 2.5 and 5 hours […]
Evidence that iron accelerates Alzheimer’s pathology: a CSF biomarker study.
OBJECTIVE: To investigate whether cerebrospinal fluid (CSF) ferritin (reporting brain iron) is associated with longitudinal changes in CSF β-amyloid (Aβ) and tau. METHODS: Mixed-effects models of CSF Aβ1-42 and tau were constructed using data from 296 participants who had baseline measurement of CSF ferritin and annual measurement of CSF tau and Aβ1-42 for up to […]
Effect of APOE Genotype on Amyloid Deposition, Brain Volume, and Memory in Cognitively Normal Older Individuals.
BACKGROUND: The association between the apolipoprotein E (APOE) ɛ4 allele and high risk of developing Alzheimer’s disease (AD) dementia before the age of 80 has been recognized for over 30 years. However, the timing and mode of action of APOE is not understood, nor has there been a detailed analysis of the effect of APOE […]
APOEɛ4 Genotype, Amyloid, and Clinical Disease Progression in Cognitively Normal Older Adults.
BACKGROUND: In cognitively normal (CN) older adults, carriage of the apolipoprotein E (APOE) ɛ4 allele is associated with increased risk for dementia of the Alzheimer type (AD-dementia). It is unclear whether this occurs solely through APOEɛ4 increasing amyloid-β (Aβ) accumulation or through processes independent of Aβ. OBJECTIVE: To determine the extent and nature to which […]
Predicting Alzheimer disease from a blood-based biomarker profile: A 54-month follow-up.
OBJECTIVE: We assessed a blood-based signature, which previously demonstrated high accuracy at stratifying individuals with high or low neocortical β-amyloid burden (NAB), to determine whether it could also identify individuals at risk of progression to Alzheimer disease (AD) within 54 months. METHODS: We generated the blood-based signature for 585 healthy controls (HCs) and 74 participants […]
Clinical and cognitive trajectories in cognitively healthy elderly individuals with suspected non-Alzheimer’s disease pathophysiology (SNAP) or Alzheimer’s disease pathology: a longitudinal study.
BACKGROUND: Brain amyloid β (Aβ) deposition and neurodegeneration have been documented in about 50-60% of cognitively healthy elderly individuals (aged 60 years or older). The long-term cognitive consequences of the presence of Alzheimer’s disease pathology and neurodegeneration, and whether they have an independent or synergistic effect on cognition, are unclear. We aimed to characterise the […]
Performance on the Cogstate Brief Battery Is Related to Amyloid Levels and Hippocampal Volume in Very Mild Dementia.
In a group of older adults with very mild dementia, we aimed to characterize the nature and magnitude of cognitive decline as measured by the Cogstate Brief Battery, in relation to Aβ levels and hippocampal volume. Participants were characterized according to their status on the Clinical Dementia Rating (CDR) scale. A total of 308 individuals […]
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