Objective
Our objectives were to characterize the inter‐relation of known dementia‐related neuropathologies in one comprehensive model and quantify the extent to which accumulation of ...neuropathologies accounts for the association between age and dementia.
Methods
We used data from 1,362 autopsied participants of three community‐based clinicopathological cohorts: the Religious Orders Study, the Rush Memory and Aging Project, and the Minority Aging Research Study. We estimated a series of structural equation models summarizing a priori hypothesized neuropathological pathways between age and dementia risk individually and collectively.
Results
At time of death (mean age, 89 years), 44% of our sample had a clinical dementia diagnosis. When considered individually, our vascular, amyloid/tau, neocortical Lewy body, and TAR DNA‐binding protein 43 (TDP‐43)/hippocampal sclerosis pathology pathways each accounted for a substantial proportion of the association between age and dementia. When considered collectively, the four pathways fully accounted for all variance in dementia risk previously attributable to age. Pathways involving amyloid/tau, neocortical Lewy bodies, and TDP‐43/hippocampal sclerosis were interdependent, attributable to the importance of amyloid beta plaques in all three. The importance of the pathways varied, with the vascular pathway accounting for 32% of the association between age and dementia, wheraes the remaining three inter‐related degenerative pathways together accounted for 68% (amyloid/tau, 24%; the Lewy body, 1%; and TDP‐43/hippocampal sclerosis, 43%).
Interpretation
Age‐related increases in dementia risk can be attributed to accumulation of multiple pathologies, each of which contributes to dementia risk. Multipronged approaches may be necessary if we are to develop effective therapies. Ann Neurol 2018;84:10–22
High amyloid has been associated with substantial episodic memory decline over 18 and 36 months in healthy older adults and individuals with mild cognitive impairment. However, the nature and ...magnitude of amyloid-related memory and non-memory change from the preclinical to the clinical stages of Alzheimer's disease has not been evaluated over the same time interval. Healthy older adults (n = 320), individuals with mild cognitive impairment (n = 57) and individuals with Alzheimer's disease (n = 36) enrolled in the Australian Imaging, Biomarkers and Lifestyle study underwent at least one positron emission tomography neuroimaging scan for amyloid. Cognitive assessments were conducted at baseline, and 18- and 36-month follow-up assessments. Compared with amyloid-negative healthy older adults, amyloid-positive healthy older adults, and amyloid-positive individuals with mild cognitive impairment and Alzheimer's disease showed moderate and equivalent decline in verbal and visual episodic memory over 36 months (d's = 0.47-0.51). Relative to amyloid-negative healthy older adults, amyloid-positive healthy older adults showed no decline in non-memory functions, but amyloid-positive individuals with mild cognitive impairment showed additional moderate decline in language, attention and visuospatial function (d's = 0.47-1.12), and amyloid-positive individuals with Alzheimer's disease showed large decline in all aspects of memory and non-memory function (d's = 0.73-2.28). Amyloid negative individuals with mild cognitive impairment did not show any cognitive decline over 36 months. When non-demented individuals (i.e. healthy older adults and adults with mild cognitive impairment) were further dichotomized, high amyloid-positive non-demented individuals showed a greater rate of decline in episodic memory and language when compared with low amyloid positive non-demented individuals. Memory decline does not plateau with increasing disease severity, and decline in non-memory functions increases in amyloid-positive individuals with mild cognitive impairment and Alzheimer's disease. The combined detection of amyloid positivity and objectively-defined decline in memory are reliable indicators of early Alzheimer's disease, and the detection of decline in non-memory functions in amyloid-positive individuals with mild cognitive impairment may assist in determining the level of disease severity in these individuals. Further, these results suggest that grouping amyloid data into at least two categories of abnormality may be useful in determining the disease risk level in non-demented individuals.
Abstract Introduction Three18 F-labeled radiopharmaceuticals have been Food and Drug Administration-approved for the identification of cortical amyloidosis in clinical settings. Although there has ...been strong debate among professionals as to the ethical and social consequences of disclosing such information, increasing numbers of participants are being recruited into secondary prevention trials for which they are likely to, and/or desire to, receive their positron emission tomography (PET) imaging results. Methods Healthy older adults (n = 63, mean age = 62 years) enrolled in a preclinical Alzheimer's disease (AD) biomarkers trial, and 11 requested disclosure of PET amyloid imaging results to their treating neurologist, per institutional review board–approved study protocol. These individuals completed a follow-up psychoeducational program and structured interviews to assess impact of disclosure on several key psychological factors. Results Four of 11 subjects demonstrated increased amyloid aggregation and reported that they were not surprised, particularly given their family histories and subjective memory concerns. All indicated that they had shared this information with pertinent significant others; they were satisfied with their level of social support, and the imaging results had motivated them to change their lifestyle by exercising more, changing their diet, and planning ahead. Amyloid-positive participants showed little change in levels of depressive, anxiety, and stress symptoms, subjective sense of memory impairment, or on measures of intrusion, avoidance, and hyperarousal, and reported risk of self-harm. Discussion Disclosure of PET amyloid status did not significantly impact mood, subjective sense of memory impairment, or perceived risk of developing AD; nor was this associated with significant emotional impact, irrespective of actual amyloid burden status. Those subjects with increased amyloid burden were more likely than those without significant amyloidosis to make positive changes to their lifestyle (e.g., engaging in more exercise and changing their diet).
Coronavirus (COVID-19) instigated unprecedented global effects on healthcare systems, economies, employment, education, travel, and social lives. In addition to increased mental health challenges, ...pandemic restrictions have triggered emerging cognitive concerns. University students are at particularly high risk of adverse lockdown-related effects, yet despite the substantial adaptions to learning necessitated by COVID-19, limited research has so far focused on the cognitive consequences of the pandemic among university students. This study aimed to comprehensively examine the nature, prevalence, and correlates of subjective cognitive concerns among 972 students (Median age = 22 years, 70% female) enrolled at Monash University, Australia, in December 2020.
Students completed the online THRIVE@Monash survey, 5 weeks following prolonged lockdown in Melbourne. Using group comparisons and hierarchical binary logistic regression analyses, we examined associations between demographic and enrolment characteristics, COVID-19-related experiences and impacts (author-developed questions), self-reported anxiety and depression symptoms (PROMIS Anxiety and Depression scales), and students' perceived changes in everyday cognitive functions (author-developed questions).
Over 60% of students reported subjective cognitive concerns (SCCs). After controlling for anxiety and depression symptoms, students reporting more SCCs were more likely to be younger, from White/European ethnic backgrounds, and in their first year of undergraduate study. No differences in SCCs were found between male and female students. Greater worry, anxiety, or stress related to COVID-19 (e.g., infection, leaving the house, hygiene and exposure prevention, impact on physical and mental health), and time spent reading or talking about COVID-19, were generally not associated with SCCs after controlling for anxiety and depression symptoms.
These findings highlight vulnerable subgroups of students who might benefit from regular monitoring, education, and interventions to support their cognitive health during the pandemic and beyond. In addition, cognitive concerns may provide additional insight into mental health problems among students, and emphasize the importance of understanding factors that impact students' long-term academic and career success.
The aim of this study was to validate the CogState Brief Battery, which assesses psychomotor, attentional, working memory, and visual learning functions, in healthy older people and in patients with ...mild cognitive impairment (MCI) and Alzheimer's disease (AD), enrolled in the Australian Imaging, Biomarkers and Lifestyle (AIBL) study. In healthy older adults, weak relationships between demographic variables (e.g., education, depression) and cognitive performance were observed. In AD and MCI groups, the magnitude of impairment was greatest for tasks of working memory and memory, with a negative influence of apolipoprotein E ϵ4 status on learning but not working memory. These results suggest that the CogState Brief Battery can be used to screen for AD-related cognitive changes.
Cross-sectional genetic association studies have reported equivocal results on the relationship between the brain-derived neurotrophic factor (BDNF) Val66Met and risk of Alzheimer's disease (AD). As ...AD is a neurodegenerative disease, genetic influences may become clearer from prospective study. We aimed to determine whether BDNF Val66Met polymorphism influences changes in memory performance, hippocampal volume, and Aβ accumulation in adults with amnestic mild cognitive impairment (aMCI) and high Aβ.
Thirty-four adults with aMCI were recruited from the Australian, Imaging, Biomarkers and Lifestyle (AIBL) Study. Participants underwent PiB-PET and structural MRI neuroimaging, neuropsychological assessments and BDNF genotyping at baseline, 18 month, and 36 month assessments.
In individuals with aMCI and high Aβ, Met carriers showed significant and large decline in episodic memory (d = 0.90, p = .020) and hippocampal volume (d = 0.98, p = .035). BDNF Val66Met was unrelated to the rate of Aβ accumulation (d = -0.35, p = .401).
Although preliminary due to the small sample size, results of this study suggest that high Aβ levels and Met carriage may be useful prognostic markers of accelerated decline in episodic memory, and reductions in hippocampal volume in individuals in the prodromal or MCI stage of AD.
Although the APOE ε4 allele is associated with more rapid decline in memory in healthy older adults, the significance of elevated cerebral β-amyloid (Aβ) load for longitudinal changes in cognition is ...unclear.
Healthy and cognitively normal older adults (n = 141; mean age 76 years) underwent PET neuroimaging for cerebral Aβ, APOE genotyping, and cognitive assessment as part of their baseline assessment in the Australian Imaging Biomarkers and Lifestyle study. Cognitive function was reassessed 18 months later.
Linear mixed-model analyses adjusted for baseline cognitive function indicated that, relative to individuals with low cerebral Aβ, individuals with high cerebral Aβ showed significantly greater decline in working memory and verbal and visual episodic memory at 18 months. Compared with noncarriers, APOE ε4 carriers showed a greater decline in visual memory at the 18-month assessment. No interaction between APOE ε4 and cerebral Aβ load was observed for any measure of cognitive function.
In this prospective study of healthy older adults, high cerebral Aβ load was associated with greater decline in episodic and working memory over 18 months. The APOE ε4 genotype was also associated with a decline in visual memory, although the effect was less than that observed for cerebral Aβ load.
Introduction: Despite the numerous episodic memory tasks used in neuropsychological assessment, relatively few learning tasks are available, with methods lacking the complexity and sophistication to ...capture very subtle changes in information acquisition.
Method: We adapted a previously validated associative learning task for use within an online framework, utilizing real-world stimuli, in which learning of audio-visual pairs of Chinese characters and English words occurs over 5 days. The aim of this study was to validate our adaptation to the task, provide estimates of rates of learning in both young and older adults, as well as provide a methodological framework for further adaptation and development of the paradigm. A total of 30 young adults and 30 older adults completed 5 days of the Chinese Characters Learning Task (CCLT).
Results: Results indicated that rates of learning on the adapted task were comparable to the original paradigm and consistent across variations to testing frequency and duration. Our results also indicate the presence of a significant age-related impairment in the rate and accuracy of learning, with young adults aged 18-45 years performing significantly better than older adults aged 65-85 years, that was not due to differences in reaction time.
Conclusions: These findings suggest that daily measurement of cognition via an online platform can detect age-related impairments in learning and is therefore applicable for use within the context of age-related disorders of memory and learning.
Background:
It has been proposed that only mild cognitive impairment (MCI) with high Aβ amyloid is indicative of incipient Alzheimer's disease (AD), yet MCI with low Aβ amyloid may reflect other ...neurodegenerative processes. We aimed to determine the extent to which high Aβ amyloid influenced cognitive function in healthy older adults and adults with MCI.
Method:
Healthy controls (HC;
n
= 178) and adults with MCI (
n
= 56) enrolled in the Australian Imaging, Biomarkers, and Lifestyle study, underwent positron emission tomography neuroimaging for Aβ amyloid and completed an extensive neuropsychological battery, assessing the cognitive domains of verbal and visual episodic memory, executive function, visuoconstruction, attention and processing speed, and language at baseline.
Results:
MCI with low Aβ performed worse than MCI with high Aβ on measures of executive function, attention, visuoconstruction and language. No differences were observed between HC high and low Aβ groups. When compared with HC with low Aβ, both MCI high and low Aβ groups performed worse on measures of episodic memory. However, only the MCI low Aβ group performed worse than HC low Aβ on measures of executive function, attention, visuoconstruction, and language.
Conclusions:
When compared with HC with low Aβ amyloid, MCI with high Aβ amyloid present with impairments restricted to episodic memory, and the episodic memory impairments in MCI with low Aβ amyloid were accompanied by impairments in executive function, attention, visuoconstruction, and language, suggesting that MCI with high Aβ amyloid reflects prodromal AD, although further longitudinal data is required to confirm this.
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