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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.

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.

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.

Background Everyday functioning is a clinically relevant concept in dementia, yet little is known about the clinical meaningfulness of scores on functional outcome measures. We aimed to establish clinically meaningful scoring categories for the Amsterdam Instrumental Activities of Daily Living Questionnaire (A-IADL-Q), representing no, mild, moderate and severe problems in daily functioning. Methods Informal caregivers ( n  = 6) of memory-clinic patients and clinicians ( n  = 13), including neurologists and nurse specialists, working at various memory clinics in The Netherlands. In focus groups, participants individually ranked nine summaries of fictional patients from least to most impairment in daily functioning. Then, they placed bookmarks to demarcate the thresholds for mild, moderate and severe problems. Individual bookmark placements were then discussed to reach consensus. Clinicians completed a survey in which they placed bookmarks, individually. Results While individual categorizations varied somewhat, caregivers and clinicians generally agreed on the thresholds, particularly about the distinction between ‘no’ and ‘mild’ problems. Score categories were no problems ( T -score ≥ 60), mild problems ( T -score 50–59), moderate problems ( T -score 40–49), and severe problems in daily functioning ( T -score < 40), on a scale ranging 20–80. Conclusions Our findings provide categories for determining the level of functional impairment, which can facilitate interpretation of A-IADL-Q scores. These categories can subsequently be used by clinicians to improve communication with patients and caregivers.

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.

Purpose Being able to function independently in society is an important aspect of quality of life. This ability goes beyond self-care, requires higher order cognitive functioning, and is typically measured with instrumental activities of daily living (IADL) questionnaires. Cognitive deficits are frequently observed in brain tumour patients, however, IADL is almost never assessed because no valid and reliable IADL measure is available for this patient group. Therefore, this measure is currently being developed. Methods This international multicentre study followed European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Group module development guidelines. Three out of four phases are completed: phases (I) generation of items, (II) construction of the item list, and (III) pre-testing. This paper reports the item selection procedures and preliminary psychometric properties of the questionnaire. Brain tumour patients (gliomas and brain metastases), their informal caregivers, and health care professionals (HCPs) were included. Results Phase I ( n  = 44 patient-proxy dyads and 26 HCPs) generated 59 relevant and important activities. In phase II, the activities were converted into items. In phase III ( n  = 85 dyads), the 59 items were pre-tested. Item selection procedures resulted in 32 items. Exploratory factor analysis revealed a preliminary dimensional structure consisting of five scales with acceptable to excellent internal consistency ( α  = 0.73–0.94) and two single items. For three scales, patients with cognitive impairments had significantly more IADL problems than patients without impairments. Conclusion A phase IV validation study is needed to confirm the psychometric properties of the EORTC IADL-BN32 questionnaire in a larger international sample.

Background 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. Methods 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. Results 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. Conclusions 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.

To propose a set of internationally harmonized procedures and methods for assessing neurocognitive functions, smell, taste, mental, and psychosocial health, and other factors in adults formally diagnosed with COVID-19 (confirmed as SARS-CoV-2 + WHO definition). We formed an international and cross-disciplinary NeuroCOVID Neuropsychology Taskforce in April 2020. Seven criteria were used to guide the selection of the recommendations' methods and procedures: (i) Relevance to all COVID-19 illness stages and longitudinal study design; (ii) Standard, cross-culturally valid or widely available instruments; (iii) Coverage of both direct and indirect causes of COVID-19-associated neurological and psychiatric symptoms; (iv) Control of factors specifically pertinent to COVID-19 that may affect neuropsychological performance; (v) Flexibility of administration (telehealth, computerized, remote/online, face to face); (vi) Harmonization for facilitating international research; (vii) Ease of translation to clinical practice. The three proposed levels of harmonization include a screening strategy with telehealth option, a medium-size computerized assessment with an online/remote option, and a comprehensive evaluation with flexible administration. The context in which each harmonization level might be used is described. Issues of assessment timelines, guidance for home/remote assessment to support data fidelity and telehealth considerations, cross-cultural adequacy, norms, and impairment definitions are also described. The proposed recommendations provide rationale and methodological guidance for neuropsychological research studies and clinical assessment in adults with COVID-19. We expect that the use of the recommendations will facilitate data harmonization and global research. Research implementing the recommendations will be crucial to determine their acceptability, usability, and validity.

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.

The Amsterdam Instrumental Activities of Daily Living Questionnaire (A-IADL-Q) is well validated and commonly used to assess difficulties in everyday functioning regarding dementia. To facilitate interpretation and clinical implementation across different European countries, we aim to provide normative data and a diagnostic cutoff for dementia. Cross-sectional data from Dutch Brain Research Registry ( = 1,064; mean ( ) age = 62 ± 11 year; 69.5% female), European Medial Information Framework-Alzheimer's Disease 90 + ( = 63; Mage = 92 ± 2 year; 52.4% female), and European Prevention of Alzheimer's Dementia Longitudinal Cohort Study ( = 247; Mage = 63 ± 7 year; 72.1% female) were used. The generalized additive models for location, scale, and shape framework were used to obtain normative values ( -scores). The beta distribution was applied, and combinations of age, sex, and educational attainment were modeled. The optimal cutoff for dementia was calculated using area under receiver operating curves (AUC-ROC) and Youden Index, using data from Amsterdam Dementia Cohort ( = 2,511, Mage = 64 ± 8 year, 44.4% female). The best normative model accounted for a cubic-like decrease of IADL performance with age that was more pronounced in low compared to medium/high educational attainment. The cutoff for dementia was 1.85 standard deviation below the population mean (AUC = 0.97; 95% CI [0.97-0.98]). We provide regression-based norms for A-IADL-Q and a diagnostic cutoff for dementia, which help improve clinical assessment of IADL performance across European countries.