A growing awareness about brain health and Alzheimer's disease in the general population is leading to an increasing number of cognitively unimpaired individuals, who are concerned that they have ...reduced cognitive function, to approach the medical system for help. The term subjective cognitive decline (SCD) was conceived in 2014 to describe this condition. Epidemiological data provide evidence that the risk for mild cognitive impairment and dementia is increased in individuals with SCD. However, the majority of individuals with SCD will not show progressive cognitive decline. An individually tailored diagnostic process might be reasonable to identify or exclude underlying medical conditions in an individual with SCD who actively seeks medical help. An increasing number of studies are investigating the link between SCD and the very early stages of Alzheimer's disease and other neurodegenerative diseases.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
There has been a growing interest in using computerized cognitive assessment to detect age-related cognitive disorders. We have developed a tablet-based cancellation test (e-CT), previously shown as ...a reliable measure of executive functions and free of effect of familiarity with computer-based devices in healthy older adults. This study aimed to investigate the influence of demographics and current daily use of computer-based devices in older adults with Mild Cognitive Impairment (MCI) and Alzheimer's disease (AD). We further studied the ability of the e-CT to discriminate MCI and AD patients from older adults with normal cognition (NC).
The e-CT was administered to 325 older adults (NC = 112, MCI = 129, AD = 84). Subjects also performed the K-T test, a paper-and-pencil cancellation test from which the e-CT was developed. Multiple linear regression analyses were conducted to assess the contribution of demographics and current daily use of computer-based devices on the e-CT in patient groups. The Receiver Operating Characteristic (ROC) curves and the Area Under the Curve (AUC) were established to compare the efficacy of the e-CT and the K-T test to classify subjects into diagnostic groups.
In the MCI group, age (B = -0.37, p<0.001) and current daily use of computer-based devices (B = 5.85, p<0.001) were associated with the number of correct cancellations of the e-CT. In the AD group, only current daily use of a computer-based device was a significant contributor (B = 6.28, p<0.001). The e-CT (AUC = 0.811; 95% confidence interval CI: 0.756-0.867) and the K-T (AUC = 0.837; CI: 0.787-0.887) showed good and comparable diagnostic accuracy to discriminate between MCI and NC subjects. To discriminate between NC and AD, both tests showed high diagnostic accuracy, with the AUC values of 0.923 (CI: 0.876-0.971) and 0.929 (95%CI: 0.886-0.972) for the e-CT and the K-T, respectively.
The e-CT presents satisfying discriminative validity and is a promising tool for detection of early cognitive impairment in older adults.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objective
Unawareness, or anosognosia, of memory deficits is a challenging manifestation of Alzheimer's disease (AD) that adversely affects a patient's safety and decision‐making. However, there is a ...lack of consensus regarding the presence, as well as the evolution, of altered awareness of memory function across the preclinical and prodromal stages of AD. Here, we aimed to characterize change in awareness of memory abilities and its relationship to beta‐amyloid (Aβ) burden in a large cohort (N = 1,070) of individuals across the disease spectrum.
Methods
Memory awareness was longitudinally assessed (average number of visits = 4.3) and operationalized using the discrepancy between mean participant and partner report on the Everyday Cognition scale (memory domain). Aβ deposition was measured at baseline using 18Fflorbetapir positron emission tomographic imaging.
Results
Aβ predicted longitudinal changes in memory awareness, such that awareness decreased faster in participants with increased Aβ burden. Aβ and clinical group interacted to predict change in memory awareness, demonstrating the strongest effect in dementia participants, but could also be found in the cognitively normal (CN) participants. In a subset of CN participants who progressed to mild cognitive impairment (MCI), heightened memory awareness was observed up to 1.6 years before MCI diagnosis, with memory awareness declining until the time of progression to MCI (−0.08 discrepant‐points/yr). In a subset of MCI participants who progressed to dementia, awareness was low initially and continued to decline (−0.23 discrepant‐points/yr), reaching anosognosia 3.2 years before dementia onset.
Interpretation
Aβ burden is associated with a progressive decrease in self‐awareness of memory deficits, reaching anosognosia approximately 3 years before dementia diagnosis. ANN NEUROL 2020;87:267–280
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Patients with gliomas often experience cognitive deficits, including problems with attention and memory. This randomized, controlled trial evaluated the effects of a multifaceted cognitive ...rehabilitation program (CRP) on cognitive functioning and selected quality-of-life domains in patients with gliomas.
One hundred forty adult patients with low-grade and anaplastic gliomas, favorable prognostic factors, and both subjective cognitive symptoms and objective cognitive deficits were recruited from 11 hospitals in the Netherlands. Patients were randomly assigned to an intervention group or to a waiting-list control group. The intervention incorporated both computer-based attention retraining and compensatory skills training of attention, memory, and executive functioning. Participants completed a battery of neuropsychological (NP) tests and self-report questionnaires on cognitive functioning, fatigue, mental health-related quality of life, and community integration at baseline, after completion of the CRP, and at 6-month follow-up.
At the immediate post-treatment evaluation, statistically significant intervention effects were observed for measures of subjective cognitive functioning and its perceived burden but not for the objective NP outcomes or for any of the other self-report measures. At the 6-month follow-up, the CRP group performed significantly better than the control group on NP tests of attention and verbal memory and reported less mental fatigue. Group differences in other subjective outcomes were not significant at 6 months.
The CRP has a salutary effect on short-term cognitive complaints and on longer-term cognitive performance and mental fatigue. Additional research is needed to identify which elements of the intervention are most effective.
We aimed to describe the Subjective Cognitive Impairment Cohort (SCIENCe) study design, to cross-sectionally describe participant characteristics, and to evaluate the SCD-plus criteria.
The SCIENCe ...is a prospective cohort study of subjective cognitive decline (SCD) patients. Participants undergo extensive assessment, including cerebrospinal fluid collection and optional amyloid positron emission tomography scan, with annual follow-up. The primary outcome measure is clinical progression.
Cross-sectional evaluation of the first 151 participants (age 64 ± 8, 44% female, Mini-Mental State Examination 29 ± 2) showed that 28 (25%) had preclinical Alzheimer's disease (AD) (amyloid status available n = 114 (75%)), 58 (38%) had subthreshold psychiatry, and 65 (43%) had neither. More severe subjective complaints were associated with worse objective performance. The SCD-plus criteria age ≥ 60 (OR 7.7 (95% CI 1.7-38.9)) and apolipoprotein E (genotype) e4 (OR 4.8 (95% CI 1.6-15.0)) were associated with preclinical AD.
The SCIENCe study confirms that SCD is a heterogeneous group, with preclinical AD and subthreshold psychiatric features. We found a number of SCD-plus criteria to be associated with preclinical AD. Further inclusion and follow-up will address important questions related to SCD.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Abstract
Introduction
The level of function of instrumental activities of daily living (IADL) is crucial for a person’s autonomy. A clear understanding of the nature of IADL and its limitations in ...people with mild cognitive impairment (MCI) is lacking. Literature suggests numerous possible influencing factors, e.g. cognitive function, but has not considered other domains of human functioning, such as environmental factors. Our aim was to develop a comprehensive model of IADL functioning that depicts the relevant influencing factors.
Methods
We conducted a four-round online Delphi study with a sample of international IADL experts (
N
= 69). In the first round, panelists were asked to mention all possible relevant cognitive and physical function factors, as well as environmental and personal factors, that influence IADL functioning. In the subsequent rounds, panelists rated the relevance of these factors. Consensus was defined as: 1) ≥70% agreement between panelists on a factor, and 2) stability over two successive rounds.
Results
Response rates from the four rounds were high (83 to 100%). In the first round, 229 influencing factors were mentioned, whereof 13 factors reached consensus in the subsequent rounds. These consensual factors were used to build a model of IADL functioning. The final model included: five cognitive function factors (i.e. memory, attention, executive function, and two executive function subdomains -problem solving / reasoning and organization / planning); five physical function factors (i.e. seeing functions, hearing functions, balance, gait / mobility functions and functional mobility functions); two environmental factors (i.e. social network / environment and support of social network / environment); and one personal factor (i.e. education).
Conclusions
This study proposes a comprehensive model of IADL functioning in people with MCI. The results from this Delphi study suggest that IADL functioning is not merely affected by cognitive function factors, but also by physical function factors, environmental factors and personal factors. The multiplicity of factors mentioned in the first round also underlines the individuality of IADL functioning in people with MCI. This model may serve as a basis for future research in IADL functioning in people with MCI.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To investigate the influence of heterogeneity in disease progression for detecting treatment effects in Alzheimer disease (AD) trials, using a simulation study.
Individuals with an abnormal amyloid ...PET scan, diagnosis of mild cognitive impairment or dementia, baseline Mini-Mental State Examination (MMSE) score ≥24, global Clinical Dementia Rating (CDR) score of 0.5, and ≥1 follow-up cognitive assessment were selected from the Alzheimer's Disease Neuroimaging Initiative database (n = 302, age 73 ± 6.7; 44% female; 16.1 ± 2.7 years of education; 69%
ε4 carrier). We simulated a clinical trial by randomly assigning individuals to a "placebo" and "treatment" group and subsequently computed group differences on the CDR-sum of boxes (CDR-SB), Alzheimer's Disease Assessment Scale-cognitive subscale-13 and MMSE after 18 months follow-up. We repeated this simulation 10,000 times to determine the 95% range of effect sizes. We further studied the influence of known AD risk factors (age, sex, education,
ε4 status, CSF total tau levels) on the variability in effect sizes.
Individual trajectories on all cognitive outcomes were highly variable, and the 95% ranges of possible effect sizes at 18 months were broad (e.g., ranging from 0.35 improvement to 0.35 decline on the CDR-SB). Results of recent anti-amyloid trials mostly fell within these 95% ranges of effect sizes.
ε4 carriers and individuals with abnormal baseline tau levels showed faster decline at group level, but also greater within-group variability, as illustrated by broader 95% effect size ranges (e.g., ±0.70 points for the CDR-SB).
Individuals with early AD show heterogeneity in disease progression, which increases when stratifying on risk factors associated with progression. We provide guidance for a priori effect sizes on cognitive outcomes for detecting true change, which is crucial for future AD trials.
OBJECTIVETo investigate the relationship between the ATN classification system (amyloid, tau, neurodegeneration) and risk of dementia and cognitive decline in individuals with subjective cognitive ...decline (SCD).
METHODSWe classified 693 participants with SCD (60 ± 9 years, 41% women, Mini-Mental State Examination score 28 ± 2) from the Amsterdam Dementia Cohort and Subjective Cognitive Impairment Cohort (SCIENCe) project according to the ATN model, as determined by amyloid PET or CSF β-amyloid (A), CSF p-tau (T), and MRI-based medial temporal lobe atrophy (N). All underwent extensive neuropsychological assessment. For 342 participants, follow-up was available (3 ± 2 years). As a control population, we included 124 participants without SCD.
RESULTSFifty-six (n = 385) participants had normal Alzheimer disease (AD) biomarkers (A–T–N–), 27% (n = 186) had non-AD pathologic change (A–T–N+, A–T+N–, A–T+N+), 18% (n = 122) fell within the Alzheimer continuum (A+T–N–, A+T–N+, A+T+N–, A+T+N+). ATN profiles were unevenly distributed, with A–T+N+, A+T–N+, and A+T+N+ containing very few participants. Cox regression showed that compared to A–T–N–, participants in A+ profiles had a higher risk of dementia with a dose–response pattern for number of biomarkers affected. Linear mixed models showed participants in A+ profiles showed a steeper decline on tests addressing memory, attention, language, and executive functions. In the control group, there was no association between ATN and cognition.
CONCLUSIONSAmong individuals presenting with SCD at a memory clinic, those with a biomarker profile A–T+N+, A+T–N–, A+T+N–, and A+T+N+ were at increased risk of dementia, and showed steeper cognitive decline compared to A–T–N– individuals. These results suggest a future where biomarker results could be used for individualized risk profiling in cognitively normal individuals presenting at a memory clinic.
In subjective cognitive decline (SCD), older adults present with concerns about self-perceived cognitive decline but are found to have clinically normal function. However, a significant proportion of ...those adults are subsequently found to develop mild cognitive impairment, Alzheimer’s dementia or other neurocognitive disorder. In other cases, SCD may be associated with mood, personality, and physical health concerns. Regardless of etiology, adults with SCD may benefit from interventions that could enhance current function or slow incipient cognitive decline. The objective of this systematic review and meta-analysis, conducted in accordance with the PRISMA guidelines, is to examine the benefits of non-pharmacologic intervention (NPI) in persons with SCD. Inclusion criteria were studies of adults aged 55 + with SCD defined using published criteria, receiving NPI or any control condition, with cognitive, behavioural, or psychological outcomes in controlled trails. Published empirical studies were obtained through a standardized search of CINAHL Complete, Cochrane Central Register of Controlled Trials, MEDLINE with Full Text, PsycINFO, and PsycARTICLES, supplemented by a manual retrieval of relevant articles. Study quality and bias was determined using PEDro. Nine studies were included in the review and meta-analysis. A wide range of study quality was observed. Overall, a small effect size was found on cognitive outcomes, greater for cognitive versus other intervention types. The available evidence suggests that NPI may benefit current cognitive function in persons with SCD. Recommendations are provided to improve future trials of NPI in SCD.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Alzheimer's disease (AD) studies are increasingly targeting earlier (pre)clinical populations, in which the expected degree of observable cognitive decline over a certain time interval is reduced as ...compared to the dementia stage. Consequently, endpoints to capture early cognitive changes require refinement. We aimed to determine the sensitivity to decline of widely applied neuropsychological tests at different clinical stages of AD as outlined in the National Institute on Aging - Alzheimer's Association (NIA-AA) research framework.
Amyloid-positive individuals (as determined by positron emission tomography or cerebrospinal fluid) with longitudinal neuropsychological assessments available were included from four well-defined study cohorts and subsequently classified among the NIA-AA stages. For each stage, we investigated the sensitivity to decline of 17 individual neuropsychological tests using linear mixed models.
1103 participants (age = 70.54 ± 8.7, 47% female) were included: n = 120 Stage 1, n = 206 Stage 2, n = 467 Stage 3 and n = 309 Stage 4. Neuropsychological tests were differentially sensitive to decline across stages. For example, Category Fluency captured significant 1-year decline as early as Stage 1 (β = -.58, p < .001). Word List Delayed Recall (β = -.22, p < .05) and Trail Making Test (β = 6.2, p < .05) became sensitive to 1-year decline in Stage 2, whereas the Mini-Mental State Examination did not capture 1-year decline until Stage 3 (β = -1.13, p < .001) and 4 (β = -2.23, p < .001).
We demonstrated that commonly used neuropsychological tests differ in their ability to capture decline depending on clinical stage within the AD continuum (preclinical to dementia). This implies that stage-specific cognitive endpoints are needed to accurately assess disease progression and increase the chance of successful treatment evaluation in AD.
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