Objectives
The burden on care partners, particularly once dementia emerges, is among the greatest of all caregiving groups. This meta‐review aimed to (1) synthesis evidence on the self‐reported needs ...of care partners supporting people living with neurodegenerative disorders; (2) compare the needs according to care partner and care recipient characteristics; and (3) determine the face validity of existing care partner needs assessment tools.
Methods
We conducted a systematic review of reviews involving a thematic synthesis of care partner needs and differences in needs according to demographic and other characteristics. We then conducted a gap analysis by identifying the themes of needs from existing needs assessment tools specific to dementia and cross‐matching them with the needs derived from the thematic synthesis.
Results
Drawing on 17 published reviews, the identified range of needs fell into four key themes: (1) knowledge and information, (2) physical, social and emotional support, (3) care partner self‐care, and (4) care recipient needs. Needs may differ according to disease trajectory, relationship to the care recipient, and the demographic characteristics of the care partner and recipient. The ‘captured needs’ range between 8% and 66% across all the included needs assessment tools.
Conclusions
Current tools do not fully or adequately capture the self‐identified needs of care partners of people living with neurodegenerative disorders. Given the high burden on care partners, which has been further exacerbated by the COVID‐19 (SARS CoV‐2) pandemic, the needs assessment tools should align with the self‐reported needs of care partners throughout the caregiving trajectory to better understand unmet needs and target supportive interventions.
Key points
This is a synthesis of available research in the area of needs of care partners of people living with neurodegenerative disorders.
Needs identified by care partners fall into four broad themes (1) knowledge and information, (2) physical, social and emotional support needs, (3) care partner self‐care, and (4) care recipient needs.
This research highlights the mismatch between the care partners' needs and the needs captured by the needs assessment tools.
This meta‐review identified emerging needs that have not been explored by existing needs assessment tools and demonstrated the importance of individualized assessment of the relative importance of needs throughout the caregiving trajectory.
Apolipoprotein E (APOE)-ε4 is the major genetic risk factor for Alzheimer's disease. However, the dose-dependent impact of this allele on brain morphology of healthy individuals remains unclear.
We ...analyzed gray matter volumes (GMvs) in a sample of 533 healthy middle-aged individuals with a substantial representation of ε4-carriers (207 heterozygotes and 65 homozygotes).
We found APOE-ε4 additive GMv reductions in the right hippocampus, caudate, precentral gyrus, and cerebellar crus. In these regions, the APOE genotype interacted with age, with homozygotes displaying lower GMv after the fifth decade of life. APOE-ε4 was also associated to greater GMv in the right thalamus, left occipital gyrus, and right frontal cortex.
Our data indicate that APOE-ε4 exerts additive effects on GMv in regions relevant for Alzheimer's disease pathophysiology already in healthy individuals. These findings elucidate the mechanisms underlying the increased Alzheimer's disease risk in ε4-carriers, suggesting a dose-dependent disease vulnerability on the brain structure level.
•Apolipoprotein E (APOE)-ɛ4 is the major genetic risk for late-onset Alzheimer's disease (AD).•In AD patients, APOE-ɛ4 relates to dose-dependent gray matter atrophy.•We analyzed gray matter volumes in 533 healthy middle-aged individuals.•We found additive effects of APOE-ɛ4 on gray matter volume in several brain regions affected in AD.•The AD risk conferred by APOE-ɛ4 may be reflected on the brain structure of cognitively healthy individuals.
White matter hyperintensities (WMH) have been extensively associated with cognitive impairment and reductions in gray matter volume (GMv) independently. This study explored whether WMH lesion volume ...mediates the relationship between cerebral patterns of GMv and cognition in 521 (mean age 57.7 years) cognitively unimpaired middle‐aged individuals. Episodic memory (EM) was measured with the Memory Binding Test and executive functions (EF) using five WAIS‐IV subtests. WMH were automatically determined from T2 and FLAIR sequences and characterized using diffusion‐weighted imaging (DWI) parameters. WMH volume was entered as a mediator in a voxel‐wise mediation analysis relating GMv and cognitive performance (with both EM and EF composites and the individual tests independently). The mediation model was corrected by age, sex, education, number of Apolipoprotein E (APOE)‐ε4 alleles and total intracranial volume. We found that even at very low levels of WMH burden in the cohort (median volume of 3.2 mL), higher WMH lesion volume was significantly associated with a widespread pattern of lower GMv in temporal, frontal, and cerebellar areas. WMH mediated the relationship between GMv and EF, mainly driven by processing speed, but not EM. DWI parameters in these lesions were compatible with incipient demyelination and axonal loss. These findings lead to the reflection on the relevance of the control of cardiovascular risk factors in middle‐aged individuals as a valuable preventive strategy to reduce or delay cognitive decline.
The neuroanatomical bases of episodic memory (EM) and executive functions (EFs) have been widely addressed in patients with brain damage and in individuals with neurologic disorders. These studies ...reported that larger brain structures support better outcomes in both cognitive domains, thereby supporting the “bigger is better” account. However, relatively few studies have explored the cerebral morphological properties underlying EM and EFs in cognitively healthy individuals and current findings indicate no unitary theoretical explanation for the structure–function relationship. Moreover, existing studies have typically restricted the analyses to a priori defined regions of interest. Here we conducted unbiased voxel‐wise analysis of the associations between regional gray as well as white matter volumes (GMv; WMv) and performance in both cognitive domains in a sample of 463 cognitively intact individuals. We found that efficiency in EM was predicted by lower GMv in brain areas belonging to the default‐mode network (DMN). By contrast, EFs performance was predicted by larger GMv in a distributed set of regions, which overlapped with the executive control network (ECN). Volume of white matter bundles supporting both cross‐cortical and interhemispheric connections was positively related to processing speed. Furthermore, aging modulated the relationship between regional volumes and cognitive performance in several areas including the hippocampus and frontal cortex. Our data extend the critical role of the DMN and ECN by showing that variability in their morphological properties, and not only their activation patterns, affects EM and EFs, respectively. Moreover, our finding that aging reverts these associations supports previously advanced theories of cognitive neurodevelopment.
INTRODUCTION
We studied how biomarkers of reactive astrogliosis mediate the pathogenic cascade in the earliest Alzheimer's disease (AD) stages.
METHODS
We performed path analysis on data from 384 ...cognitively unimpaired individuals from the ALzheimer and FAmilies (ALFA)+ study using structural equation modeling to quantify the relationships between biomarkers of reactive astrogliosis and the AD pathological cascade.
RESULTS
Cerebrospinal fluid (CSF) amyloid beta (Aβ)42/40 was associated with Aβ aggregation on positron emission tomography (PET) and with CSF p‐tau181, which was in turn directly associated with CSF neurofilament light (NfL). Plasma glial fibrillary acidic protein (GFAP) mediated the relationship between CSF Aβ42/40 and Aβ‐PET, and CSF YKL‐40 partly explained the association between Aβ‐PET, p‐tau181, and NfL.
DISCUSSION
Our results suggest that reactive astrogliosis, as indicated by different fluid biomarkers, influences the pathogenic cascade during the preclinical stage of AD. While plasma GFAP mediates the early association between soluble and insoluble Aβ, CSF YKL‐40 mediates the latter association between Aβ and downstream Aβ‐induced tau pathology and tau‐induced neuronal injury.
Highlights
Lower CSF Aβ42/40 was directly linked to higher plasma GFAP concentrations.
Plasma GFAP partially explained the relationship between soluble Aβ and insoluble Aβ.
CSF YKL‐40 mediated Aβ‐induced tau phosphorylation and tau‐induced neuronal injury.
Introduction
Biological sex is an increasingly recognized factor driving clinical and structural heterogeneity in Alzheimer's disease, but its role in the behavioral variant of frontotemporal ...dementia (bvFTD) is unknown.
Methods
We included 216 patients with bvFTD and 235 controls with magnetic resonance imaging (MRI) from a large multicenter cohort. We compared the clinical characteristics and cortical thickness between men and women with bvFTD and controls. We followed the residuals approach to study behavioral and cognitive reserve.
Results
At diagnosis, women with bvFTD showed greater atrophy burden in the frontotemporal regions compared to men despite similar clinical characteristics. For a similar amount of atrophy, women demonstrated better‐than‐expected scores on executive function and fewer changes in apathy, sleep, and appetite than men.
Discussion
Our findings suggest that women might have greater behavioral and executive reserve than men, and neurodegeneration must be more severe in women to produce symptoms similar in severity to those in men.
INTRODUCTION
In 2013, the ALzheimer's and FAmilies (ALFA) project was established to investigate pathophysiological changes in preclinical Alzheimer's disease (AD), and to foster research on early ...detection and preventive interventions.
METHODS
We conducted a comprehensive genetic characterization of ALFA participants with respect to neurodegenerative/cerebrovascular diseases, AD biomarkers, brain endophenotypes, risk factors and aging biomarkers. We placed particular emphasis on amyloid/tau status and assessed gender differences. Multiple polygenic risk scores were computed to capture different aspects of genetic predisposition. We additionally compared AD risk in ALFA to that across the full disease spectrum from the Alzheimer's Disease Neuroimaging Initiative (ADNI).
RESULTS
Results show that the ALFA project has been successful at establishing a cohort of cognitively unimpaired individuals at high genetic predisposition of AD.
DISCUSSION
It is, therefore, well‐suited to study early pathophysiological changes in the preclinical AD continuum.
Highlights
Prevalence of ε4 carriers in ALzheimer and FAmilies (ALFA) is higher than in the general European population
The ALFA study is highly enriched in Alzheimer's disease (AD) genetic risk factors beyond APOE
AD genetic profiles in ALFA are similar to clinical groups along the continuum
ALFA has succeeded in establishing a cohort of cognitively unimpaired individuals at high genetic AD risk
ALFA is well suited to study pathogenic events/early pathophysiological changes in AD
White matter hyperintensities (WMH) are commonly detected in the brain of elderly individuals and have been associated with a negative impact on multiple cognitive domains. We aim to investigate the ...impact of global and regional distribution of WMH on episodic memory and executive function in middle-aged cognitively unimpaired participants
N
= 561 (45–75 years) enriched for Alzheimer’s disease risk factors. WMH were automatically segmented from FLAIR, T1 and FSE MR images. WMH load was calculated both globally and regionally. At each cerebral lobe, regional WMH load was measured at four equidistant layers extending from the lateral ventricles to juxtacortical areas. Cognition was measured by The Memory Binding Test (MBT) and WAIS-IV subtests. Global composite z-scores were calculated for the two cognitive domains. Association between global and regional WMH measurements were sought against cognitive measures, both in global composite scores and in individual subtests. We adjusted cognition and WMH burden for the main sociodemographic (age, sex and education) and genetic factors (
APOE-ε4
). Memory and executive function were significantly associated with global WMH load. Regionally, lower executive performance was mainly associated with higher deep WMH load in frontal areas and, to a lower degree, in occipital, parietal and temporal regions. Lower episodic memory performance was correlated with higher WMH burden in deep frontal and occipital areas. Our novel methodological approach of regional analysis allowed us to reveal the association between cognition and WMH in strategic brain locations. Our results suggest that, even a small WMH load can impact cognition in cognitively unimpaired middle-aged subjects.
Background
Subjective cognitive decline (SCD) is often related to affective symptoms and both predict cognitive decline. We investigated whether SCD status predicted higher anxiety/depression during ...the Covid19‐related confinement, along with amyloid positivity in cognitively unimpaired older adults.
Method
We included 205 participants from the ALFA+ study (Table 1). During the confinement, anxiety and depression (Hospital Depression and Anxiety scale, HADS), perceived stress (Perceived Stress Scale) and stress resilience (Brief Resilience Scale) were measured. Participants completed HADS, SCD‐Questionnaire, and underwent a 18Fflutemetamol‐PET scan on average 2.4 years before confinement (baseline). We ran linear analyses with (i) cross‐sectional HADS scores during the confinement as well as (ii) change from baseline to confinement (delta scores) as dependent variables. SCD and amyloid status (+/‐, defined with a Centiloid threshold of 12) and their interaction were considered as predictors, and demographics, APOE‐ε4 status, and baseline HADS (for longitudinal analyses) as covariates. In a second step, perceived stress and stress resilience were considered in the models among covariates.
Result
Twenty‐seven percent (n=56) of the participants were classified as SCD and 12.7% as amyloid positive. When main effects were tested, both SCD (p=0.03) and amyloid positivity (p=0.003) were associated with higher HADS scores during confinement (Table 2a). Further, a significant SCD*amyloid interaction was observed (p=0.001) such that only SCD participants with an amyloid positive scan showed higher HADS scores (p=0.001). SCD participants showed higher perceived stress than non‐SCD participants (p=.044), but no differences were found in stress resilience (p=0.6). The inclusion of perceived stress and stress resilience as covariates reduced the SCD effect to a trend (p=0.06) but not the effect of amyloid (p=0.003). Longitudinal analyses with delta scores showed similar results for amyloid but not for SCD main effects (Table 2b). The amyloid*SCD interaction was also significant in longitudinal analyses (p=0.002) with amyloid status predicting an increase in HADS scores only in participants with SCD (p=0.003) (Fig. 1).
Conclusion
Having SCD and being amyloid positive is synergistically related to increased anxiety/depression during the Covid19‐related confinement. Longitudinal studies are warranted to investigate the impact of higher confinement related anxiety/depression in the clinical prognosis of the SCD population.
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