Focal neural perturbations reshape low-dimensional trajectories of brain activity supporting cognitive performance.
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ABSTRACT:
SUBMITTER: Iyer KK
PROVIDER: S-EPMC8749005 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundThe presence of ß-amyloid (Aß) in the brain can be identified using amyloid PET. In clinical practice, the amyloid PET is interpreted based on dichotomous visual rating, which renders focal Aß accumulation be read as positive for Aß. However, the prognosis of patients with focal Aß deposition is not well established. Thus, we investigated cognitive trajectories of patients with focal Aß deposition.MethodsWe followed up 240 participants (112 cognitively unimpaired [CU], 78 amnestic mild cognitive impairment [aMCI], and 50 Alzheimer's disease (AD) dementia [ADD]) for 2 years from 9 referral centers in South Korea. Participants were assessed with neuropsychological tests and 18F-flutemetamol (FMM) positron emission tomography (PET). Ten regions (frontal, precuneus/posterior cingulate (PPC), lateral temporal, parietal, and striatum of each hemisphere) were visually examined in the FMM scan, and participants were divided into three groups: No-FMM, Focal-FMM (FMM uptake in 1-9 regions), and Diffuse-FMM. We used mixed-effects model to investigate the speed of cognitive decline in the Focal-FMM group according to the cognitive level, extent, and location of Aß involvement, in comparison with the No- or Diffuse-FMM group.ResultsForty-five of 240 (18.8%) individuals were categorized as Focal-FMM. The rate of cognitive decline in the Focal-FMM group was faster than the No-FMM group (especially in the CU and aMCI stage) and slower than the Diffuse-FMM group (in particular in the CU stage). Within the Focal-FMM group, participants with FMM uptake to a larger extent (7-9 regions) showed faster cognitive decline compared to those with uptake to a smaller extent (1-3 or 4-6 regions). The Focal-FMM group was found to have faster cognitive decline in comparison with the No-FMM when there was uptake in the PPC, striatum, and frontal cortex.ConclusionsWhen predicting cognitive decline of patients with focal Aß deposition, the patients' cognitive level, extent, and location of the focal involvement are important.
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Project description:The Cognitive Estimation Test (CET) is a widely used test to investigate estimation abilities requiring complex processes such as reasoning, the development and application of appropriate strategies, response plausibility checking as well as general knowledge and numeracy (e.g., Shallice and Evans, 1978; MacPherson et al., 2014). Thus far, it remains unknown whether the CET is both sensitive and specific to frontal lobe dysfunction. Neuroimaging techniques may not represent a useful methodology for answering this question since the complex processes involved are likely to be associated with a large network of brain regions, some of which are not functionally necessary to successfully carry out the CET. Instead, neuropsychological studies may represent a more promising investigation tool for identifying the brain areas necessary for CET performance. We recently developed two new versions of the CET (CET-A and CET-B; MacPherson et al., 2014). We investigated the overall performance and conducted an error analysis on CET-A in patients with focal, unilateral, frontal (n = 38) or posterior (n = 22) lesions and healthy controls (n = 39). We found that frontal patients' performance was impaired compared to healthy controls on CET. We also found that frontal patients generated significantly poorer estimates than posterior patients on CET-A. This could not be explained by impairments in fluid intelligence. The error analyses suggested that for CET-A, extreme and very extreme responses are impaired following frontal lobe damage. However, only very extreme responses are significantly more impaired following frontal lobe than posterior damage and so represent a measure restricted to frontal "executive" impairment, in addition to overall CET performance.
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Project description:ObjectivesTo examine whether trajectories of global cognitive function over time in studies that change assessment protocols may be modeled based on an individual's performance relative to others in the study cohort.DesignExtended follow-up of a cohort originally enrolled in a clinical trial of postmenopausal hormone therapy.SettingThe Women's Health Initiative Memory Study switched from an in-person interview with the Modified Mini-Mental State Examination to a telephone-based interview with the modified Telephone Interview for Cognitive Status to assess global cognitive function over long-term follow-up.ParticipantsWomen aged 75 to 92 (N=2,561).MeasurementsAnnual cognitive assessments from participants, ranked according to age-, race- and ethnicity-adjusted performance levels, were used to identify distinct trajectories. Participants assigned to the resulting trajectories were compared for selected risk factor profiles.ResultsOur approach grouped participants into five trajectories according to relative cognitive performance over time. These groups differed significantly according to 3 known risk factors for cognitive decline-education level, apolipoprotein E-ϵ4 genotype, and type 2 diabetes mellitus-and a biomarker based on brain structure that has been linked to cognitive decline and Alzheimer's disease. Participants with consistently low relative levels of cognitive function over time and those whose relative performance over time declined to these levels tended to have poorer risk factor profiles.ConclusionLongitudinal measures of an individual's relative performance on different assessment protocols for global cognitive function can be used to identify trajectories of change over time that appear to have internal validity with respect to known risk factors.
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