Prospective Evaluation of Cognitive Health and Related Factors in Elderly at Risk for Developing Alzheimer’s Dementia: A Longitudinal Cohort Study

Abstract

Background: The CHARIOT PRO Main study is a prospective, non-interventional study evaluating cognitive trajectories in participants at the preclinical stage of Alzheimer’s disease (AD) classified by risk levels for developing mild cognitive impairment due to AD (MCI-AD). Objectives: The study aimed to characterize factors and markers influencing cognitive and functional progression among individuals at-risk for developing MCI-AD, and examine data for more precise predictors of cognitive change, particularly in relation to APOE ε4 subgroup. Design: This single-site study was conducted at the Imperial College London (ICL) in the United Kingdom. Participants 60 to 85 years of age were classified as high, medium (amnestic or non-amnestic) or low risk for developing MCI-AD based on RBANS z-scores. A series of clinical outcome assessments (COAs) on factors influencing baseline cognitive changes were collected in each of the instrument categories of cognition, lifestyle exposure, mood, and sleep. Data collection was planned to occur every 6 months for 48 months, however the median follow-up time was 18.1 months due to early termination of study by the sponsor. Results: 987 participants were screened, among them 690 participants were actively followed-up post baseline, of whom 165 (23.9%) were APOE ε4 carriers; with at least one copy of the allele. The mean age was 68.73 years, 94.6% were white, 57.4% were female, and 34.8% had a Family History of Dementia with a somewhat larger percentage in the APOE ε4 carrier group (42.4%) compared to the non-carrier group (32.4%). Over half of the participants were married and 53% had a Bachelor’s or higher degree. Most frequently, safety events typical for this population consisted of upper respiratory tract infection (10.4%), falls (5.2%), hypertension (3.5%) and back pain (3.0%). Conclusion (clinical relevance): AD-related measures collected during the CHARIOT PRO Main study will allow identification and evaluation of AD risk factors and markers associated with cognitive performance from the pre-clinical stage. Evaluating the psycho-biological characteristics of these pre-symptomatic individuals in relation to their natural neurocognitive trajectories will enhance current understanding on determinants of the initial signs of cognitive changes linked to AD.

Depressive Symptoms and Cognitive Decline Among Chinese Rural Elderly Individuals: A Longitudinal Study With 2-Year Follow-Up

“…Despite relatively numerous studies on the relationship between depression and cognitive decline, a few gaps exist in the literature. First, although depression is very common among elderly individuals ( 16 ), available studies are often limited to middle-aged people ( 17 ), clinical patients ( 18 ), and urban areas ( 19 , 20 ). In addition, longitudinal studies, which are essential to investigate the causal effect of depression on the onset of cognitive decline, are still insufficient ( 21 , 22 ).…”

Joint Analysis of Genome-Wide Association Data Reveals No Genetic Correlations Between Low Back Pain and Neurodegenerative Diseases

“…Observational studies exploring the relationship between LBP and neurodegenerative diseases have been conducted before ( Broetz et al, 2007 ; Aggarwal et al, 2010 ; Miller et al, 2013 ; Udeh-Momoh et al, 2019 ; Silveira Barezani et al, 2020 ). Several studies reported a high occurrence of LBP during the non-interventional course of AD ( Udeh-Momoh et al, 2019 ), and the interventional diagnostic and therapeutic procedure of AD ( Landen et al, 2013 ; Alcolea et al, 2014 ). Similarly, LBP was a common complaint during the treatment of ALS ( Aggarwal et al, 2010 ; Miller et al, 2013 ).…”

“…Possible relationships between LBP and neurodegenerative diseases have been previously postulated ( Broetz et al, 2007 ; Aggarwal et al, 2010 ; Miller et al, 2013 ; Udeh-Momoh et al, 2019 ; Silveira Barezani et al, 2020 ). In a prospective cohort of 690 participants at the preclinical stage of AD ( Udeh-Momoh et al, 2019 ), back pain was among the most frequently occurring (3.0%) safety events, whereas in a recent cross-sectional study of 115 patients with sporadic PD ( Silveira Barezani et al, 2020 ), 58.3% of participants reported to have LBP. A higher prevalence of back pain in PD patients (75/101, 74.3%) when compared with age-matched control patients (35/132, 26.5%) was reported in another prior study ( Broetz et al, 2007 ).…”

A multi-omics approach identifies a blood-based miRNA signature of cognitive decline in two large observational trials

“…Exclusion criteria included a dementia or MCI diagnosis, presence of any neurological or psychiatric condition, substance use disorder or the presence of reversible causes of dementia. Further details can be found elsewhere 27 .…”