Reserve is a hypothetical construct that buffers the relationship between pathology and the clinical expression of aging and brain-based disorders, with cognitive reserve being the most widely ...studied. While cognitive reserve is associated with neuropsychological and neuroimaging outcomes, relatively little research has examined how measures of cognitive reserve might relate to real-world functioning, or instrumental activities of daily living (IADLs). This program of research was first interested in exploring whether cognitive reserve differentially relates to neuropsychological functioning versus IADL functioning. This is crucial for identifying possible treatment targets that may support functional independence. Random-effects meta-analyses were conducted using studies of participants diagnosed with mild cognitive impairment (k=58; n=7,871; 53% female). Common proxies of cognitive reserve (i.e., educationand occupational attainment) appeared to have limited benefits with respect to functional outcomes. Instead, a cognitive reserve proxy that better approximates IADLs (i.e., leisure activity) appeared to be more strongly associated IADL functioning. The results of this meta-analysis lead one to question whether participation in IADLs may demonstrate even stronger effects in terms of functional decline, perhaps through a functional reserve. To investigate the functional reserve hypothesis, this research program next developed the first instrument to quantify IADL experience – the Scale for Activity of Daily Living Experience (SADLE). Participants were recruited through Mechanical Turk at baseline (n=287) and 3-month follow-up (n=54). The final scale consisted of 39-items and two subscales. Test-retest reliability was excellent to good. Overall SADLE scores and participation across specific activities were associated with age, sex, domestic partnership, and gender-role identity, with effects ranging from weak to modest. The development and validation of the SADLE is an important first step in studying the functional reserve hypothesis, with further research needed in clinical samples. Finally, this research program proposed mechanisms that may underlie functional reserve – namely, cognitive, physical, psychological, and social mechanisms. In doing so, numerous future directions were provided to further validate the functional reserve hypothesis. Research that builds on this body of work may allow for the identification of individuals at risk for IADL impairment and may inform the development of interventions that are more efficacious in targeting functional decline.
INTRODUCTION
Sleep disturbances are common in Alzheimer's disease (AD) and may reflect pathologic changes in brain networks. To date, no studies have examined changes in sleep functional connectivity ...(FC) in AD or their relationship with network hyperexcitability and cognition.
METHODS
We assessed electroencephalogram (EEG) sleep FC in 33 healthy controls, 36 individuals with AD without epilepsy, and 14 individuals with AD and epilepsy.
RESULTS
AD participants showed increased gamma connectivity in stage 2 sleep (N2), which was associated with longitudinal cognitive decline. Network hyperexcitability in AD was associated with a distinct sleep connectivity signature, characterized by decreased N2 delta connectivity and reversal of several connectivity changes associated with AD. Machine learning algorithms using sleep connectivity features accurately distinguished diagnostic groups and identified “fast cognitive decliners” among study participants who had AD.
DISCUSSION
Our findings reveal changes in sleep functional networks associated with cognitive decline in AD and may have implications for disease monitoring and therapeutic development.
Highlights
Brain functional connectivity (FC) in Alzheimer's disease is altered during sleep.
Sleep FC measures correlate with cognitive decline in AD.
Network hyperexcitability in AD has a distinct sleep connectivity signature.
Background and purpose
The pathophysiology of Parkinson's disease (PD) negatively affects brain network connectivity, and in the presence of brain white matter hyperintensities (WMHs) cognitive and ...motor impairments seem to be aggravated. However, the role of WMHs in predicting accelerating symptom worsening remains controversial. The objective was to investigate whether location and segmental brain WMH burden at baseline predict cognitive and motor declines in PD after 2 years.
Methods
Ninety‐eight older adults followed longitudinally from Ontario Neurodegenerative Diseases Research Initiative with PD of 3–8 years in duration were included. Percentages of WMH volumes at baseline were calculated by location (deep and periventricular) and by brain region (frontal, temporal, parietal, occipital lobes and basal ganglia + thalamus). Cognitive and motor changes were assessed from baseline to 2‐year follow‐up. Specifically, global cognition, attention, executive function, memory, visuospatial abilities and language were assessed as were motor symptoms evaluated using the Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III, spatial–temporal gait variables, Freezing of Gait Questionnaire and Activities Specific Balance Confidence Scale.
Results
Regression analysis adjusted for potential confounders showed that total and periventricular WMHs at baseline predicted decline in global cognition (p < 0.05). Also, total WMH burden predicted the decline of executive function (p < 0.05). Occipital WMH volumes also predicted decline in global cognition, visuomotor attention and visuospatial memory declines (p < 0.05). WMH volumes at baseline did not predict motor decline.
Conclusion
White matter hyperintensity burden at baseline predicted cognitive but not motor decline in early to mid‐stage PD. The motor decline observed after 2 years in these older adults with PD is probably related to the primary neurodegenerative process than comorbid white matter pathology.
The definition of "objective cognitive impairment" in current criteria for mild cognitive impairment (MCI) varies considerably between research groups and clinics. This study aims to compare ...different methods of defining memory impairment to improve prediction models for the development of Alzheimer's disease (AD) from baseline to 24 months.
The sensitivity and specificity of six methods of defining episodic memory impairment (< -1, -1.5 or -2 standard deviations SD on one or two memory tests) were compared in 494 non-demented seniors from the Alzheimer's Disease Neuroimaging Initiative using the area under the curve (AUC) for receiver operating characteristic analysis. The added value of non-memory measures (language and executive function) and biomarkers (hippocampal and white-matter hyperintensity volume, brain parenchymal fraction BPF, and APOEε4 status) was investigated using logistic regression.
Baseline scores < -1 SD on two memory tests predicted AD with 75.91 % accuracy (AUC = 0.80). Only APOE ε4 status further improved prediction (B = 1.10, SE = 0.45, p = .016). A < -1.5 SD cut-off on one test had 66.60 % accuracy (AUC = 0.77). Prediction was further improved using Trails B/A ratio (B = 0.27, SE = 0.13, p = .033), BPF (B = -15.97, SE = 7.58, p = .035), and APOEε4 status (B = 1.08, SE = 0.45, p = .017). A cut-off of < -2 SD on one memory test (AUC = 0.77, SE = 0.03, 95 % CI 0.72-0.82) had 76.52 % accuracy in predicting AD. Trails B/A ratio (B = 0.31, SE = 0.13, p = .017) and APOE ε4 status (B = 1.07, SE = 0.46, p = .019) improved predictive accuracy.
Episodic memory impairment in MCI should be defined as scores < -1 SD below normative references on at least two measures. Clinicians or researchers who administer a single test should opt for a more stringent cut-off and collect and analyze whole-brain volume. When feasible, ascertaining APOE ε4 status can further improve prediction.
Objectives
Neuropsychiatric symptoms (NPS) increase risk of developing dementia and are linked to various neurodegenerative conditions, including mild cognitive impairment (MCI due to Alzheimer's ...disease AD), cerebrovascular disease (CVD), and Parkinson's disease (PD). We explored the structural neural correlates of NPS cross‐sectionally and longitudinally across various neurodegenerative diagnoses.
Methods
The study included individuals with MCI due to AD, (n = 74), CVD (n = 143), and PD (n = 137) at baseline, and at 2‐years follow‐up (MCI due to AD, n = 37, CVD n = 103, and PD n = 84). We assessed the severity of NPS using the Neuropsychiatric Inventory Questionnaire. For brain structure we included cortical thickness and subcortical volume of predefined regions of interest associated with corticolimbic and frontal‐executive circuits.
Results
Cross‐sectional analysis revealed significant negative correlations between appetite with both circuits in the MCI and CVD groups, while apathy was associated with these circuits in both the MCI and PD groups. Longitudinally, changes in apathy scores in the MCI group were negatively linked to the changes of the frontal‐executive circuit. In the CVD group, changes in agitation and nighttime behavior were negatively associated with the corticolimbic and frontal‐executive circuits, respectively. In the PD group, changes in disinhibition and apathy were positively associated with the corticolimbic and frontal‐executive circuits, respectively.
Conclusions
The observed correlations suggest that underlying pathological changes in the brain may contribute to alterations in neural activity associated with MBI. Notably, the difference between cross‐sectional and longitudinal results indicates the necessity of conducting longitudinal studies for reproducible findings and drawing robust inferences.
Key points
What is the primary question addressed by this study?
The structural neural correlates of neuropsychiatric symptoms (NPS) in multiple neurodegenerative diagnoses.
What is the main finding of this study?
Our study reveals the involvement of both corticolimbic and frontal‐executive circuits in three populations at risk for developing dementia, with these circuits showing significant associations with NPS. The distinct neural correlates were observed within each population, shedding light on the neurobiological mechanisms underlying NPS in these disorders and providing a better understanding of their progression toward dementia.
What is the meaning of the finding?
These results have significant implications for the early detection and management of NPS in patients with neurodegenerative disorders and may inform the development of more effective treatment strategies in the future. Furthermore, the difference between cross‐sectional and longitudinal results indicates the necessity of conducting longitudinal studies for reproducible findings and drawing robust inferences.
Background
Acute change in gait speed while performing a mental task dual-task gait cost (DTC), and hyperintensity magnetic resonance imaging signals in white matter are both important disability ...predictors in older individuals with history of stroke (poststroke). It is still unclear, however, whether DTC is associated with overall hyperintensity volume from specific major brain regions in poststroke.
Methods
This is a cohort study with a total of 123 older (69 ± 7 years of age) participants with history of stroke were included from the Ontario Neurodegenerative Disease Research Initiative. Participants were clinically assessed and had gait performance assessed under single- and dual-task conditions. Structural neuroimaging data were analyzed to measure both, white matter hyperintensity (WMH) and normal appearing volumes. Percentage of WMH volume in frontal, parietal, occipital, and temporal lobes as well as subcortical hyperintensities in basal ganglia + thalamus were the main outcomes. Multivariate models investigated associations between DTC and hyperintensity volumes, adjusted for age, sex, years of education, global cognition, vascular risk factors, APOE4 genotype, residual sensorimotor symptoms from previous stroke and brain volume.
Results
There was a significant positive global linear association between DTC and hyperintensity burden (adjusted Wilks’ λ = .87, P = .01). Amongst all WMH volumes, hyperintensity burden from basal ganglia + thalamus provided the most significant contribution to the global association (adjusted β = .008, η2 = .03; P = .04), independently of brain atrophy.
Conclusions
In poststroke, increased DTC may be an indicator of larger white matter damages, specifically in subcortical regions, which can potentially affect the overall cognitive processing and decrease gait automaticity by increasing the cortical control over patients’ locomotion.
Abstract
Background
Mild behavioral impairment (MBI) is a syndrome characterized by later life onset, persistent neuropsychiatric symptoms (NPS) in non‐demented older adults. MBI can co‐occur with ...Mild Cognitive Impairment (MCI) and has a range of neurodegenerative etiologies including Alzheimer’s disease (AD), Cerebrovascular Disease (CVD), and Parkinson’s disease (PD). MBI is associated with poorer cognitive and psychosocial function and an increased risk of developing dementia. Thus, we aimed to explore the structural neural correlates of MBI, specifically in the regions known to be associated with cognitive impairment (i.e., corticolimbic and frontal‐executive circuits), across multiple neurodegenerative diagnoses from the Ontario Neurodegenerative Disease Research Initiative (ONDRI).
Method
We assessed the association between MBI and brain structural alterations via T1‐weighted imaging in three groups with Montreal Cognitive Assessment scores ³19: individuals with MCI (due to AD; n = 37), CVD (n = 129), and PD (n = 127). NPS scores were derived from the Neuropsychiatric Inventory (NPI‐Q) domains, and categorized as NPS+ (i.e., NPI score>0); and NPS‐ (NPI score = 0). We selected regions of interest from the corticolimbic and frontal‐executive circuits to measure brain structure using cortical thickness and subcortical volume. Partial correlation, corrected for age, sex, and education was used to assess the association between MBI and brain structural alterations.
Result
Overall, apathy, depression, and anxiety, which map to the decreased motivation and emotional dysregulation MBI domains, had a high prevalence across all the groups. In the brain‐MBI association analysis, apathy was associated with decreased thickness of the l‐rostral middle frontal, r‐superior temporal, and frontal pole in the PD and CVD (but not MCI) groups. Anxiety was associated with decreased volume of the right hippocampus and amygdala in the MCI group, but not CVD or PD (FDR p< 0.05). No structural correlates were found for depression.
Conclusion
Our findings provide evidence of a specific association between apathy and reduced efficiency of the frontal‐executive system in individuals with PD and CVD. In addition, the well‐established AD corticolimbic atrophy patterns (e.g., hippocampus and amygdala) seen in MCI are prominent in the presence of anxiety. Overall, the relatively distinct brain‐MBI associations across neurodegenerative disorders suggest that pathological substrates may alter MBI neural correlates.
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