The Lifestyle Intervention in memory clinics of General and academic Hospitals Trial (LIGHT): Rationale and study design of a randomized controlled trial to reduce modifiable dementia risk.

BackgroundDementia risk reduction through lifestyle modification has much potential but is not widely implemented in routine care. Patients referred to memory clinics are at high risk for dementia and tend to have worse health and lifestyle profiles. There is currently no service available to help these persons make lifestyle changes. We aim to improve lifestyle profiles through implementing a personalized and multidomain lifestyle intervention in the memory clinic. Here, we describe the design of our study assessing the effectiveness of this intervention.MethodLifestyle Intervention in the memory clinics of General and academic Hospitals Trial (LIGHT) is a 12‐month multicentre randomized controlled trial investigating the effects of an innovative lifestyle intervention. Starting early 2025, the trial aims to include 300 older adults (≥ 50 years) with subjective cognitive decline (SCD) or mild cognitive impairment (MCI) who have ≥2 modifiable dementia risk factors (to ensure room for improvement) primarily from the memory clinics of Maastricht UMC+ and Amsterdam UMC. Participants are randomized 1:1 to the intervention or usual care with general health advice. The intervention comprises three components: 1) Three individual sessions with a certified lifestyle coach to work on personal goals, 2) Vouchers for access to brain‐healthy activities from local providers, and 3) Online access to a recently developed risk self‐management platform (www.breinzorg.nl). Primary outcome is the 12‐month change in participants dementia risk profiles as measured by the LIfestyle for BRAin Health (LIBRA) index. Secondary outcomes include cognitive functioning, health‐related quality of life, activities of daily living, psychological measures, as well as individual lifestyle components.ResultLIGHT provides insight into the implementability and (cost‐) effectiveness of a lifestyle intervention in a memory clinic setting. Recruitment has started early 2025 and will continue until 2027.ConclusionLIGHT may provide evidence for a personalized multidomain lifestyle intervention for preventing dementia. The results would support implementing personalized lifestyle coaching in the regular service offered by Dutch memory clinics.

BackgroundPlasma biomarkers as a new approach in Alzheimer’s screening and diagnostics are time‐ and cost‐saving. Blood sampling is easier, less risky, and less invasive than other well‐established diagnostic tools, such as cerebrospinal fluid biomarkers (CSF), and is well tolerated by patients. The goal of this study was to test whether and to what extent plasma biomarkers are suitable for the differentiation between the clinical diagnostic groups dementia of Alzheimer’s type (DAT), mild cognitive impairment (MCI) and subjective cognitive decline (SCD) in a routine care memory clinic.MethodWe examined plasma samples of 144 memory clinic patients. Plasma biomarkers were measured through ultrasensitive Single molecule array (Simoa) immunoassay technology. The concentrations of amyloid‐beta42 (Aß42), amyloid‐beta40 (Aß40), phospho‐Tau181 (pTau181), total‐Tau (tTau) and neurofilament‐light (NF‐L) were determined. Statistical analysis, including receiver operating characteristics (ROC) analyses, were performed. Possible cut‐off values are discussed.ResultThrough Aß40 a weak differentiation between SCD and DAT (AUC=0.64) and through Aß42/Aß40 a weak differentiation between SCD and MCI (AUC=0.64), SCD and MCI+DAT (AUC=0.66) and SCD and DAT (AUC=0.67) was possible. PTau181 was able to distinguish between diagnostic groups and showed a weak differentiation between MCI and DAT (AUC=0.69), a strong differentiation between SCD and MCI+DAT (AUC=0.78) and SCD and MCI (AUC=0.72) and an excellent differentiation between SCD and DAT (AUC=0.85). NF‐L weakly distinguished between SCD and MCI+DAT (AUC=0.70) and MCI and DAT (AUC=0.72), but strongly distinguished between SCD and DAT (AUC=0.81). At a cut‐off point of 10.2pg/ml pTau181 showed a sensitivity of 89% and a specificity of 73% to distinguish between SCD and DAT.ConclusionPlasma Aß40, Aß42/Aß40, pTau181 and NF‐L analyzed with the Simoa technology proved to be promising future diagnostic and screening tools in a routine memory clinic setting outside of specific research studies. While amyloid markers showed only moderate discrimination between the groups, pTau181 and NF‐L clearly distinguished between SCD and the more progressed stages of MCI and DAT. These findings agree with the current model of amyloid build‐up already before significant clinical symptoms, and pTau and neurodegeneration correlating with symptomatic progression. In our data, pTau181 provided the best discrimination between the diagnostic groups.

BackgroundMany studies showed that addressing modifiable risk factors has an impact on dementia prevalence and incidence. Most studies have focussed on universal prevention, irrespective of individual risk stage, with risk factors for dementia mainly identified in the general population. Less is known about the most important target risk factors in persons with subjective cognitive decline (SCD) or mild cognitive impairment (MCI), and hence, whether they have a similar potential for risk reduction as the general population. Therefore, this study aims to identify modifiable risk and protective factors for cognitive deterioration and dementia in persons with SCD or MCI.MethodWe use a mixed‐methods approach combining findings from a systematic literature review and an online Delphi study. Four electronic databases (PubMed, EMBASE, PsycINFO, Web of Science) were searched to review relevant literature. A broad search term was developed in consultation with an experienced librarian and consisted of terms linked to SCD, MCI, dementia, modifiable risk factors and disease progression. Observational studies with at least 50 participants and 1 year of follow‐up were considered for inclusion. Twenty international dementia prevention experts were invited to participate in the online Delphi study. In two rounds, experts were asked to spontaneously name, rank and weigh modifiable risk and protective factors in order of importance for the target population.ResultOur search yielded 19,128 abstracts in total. After removal of duplicates, 9,862 abstracts were considered for inclusion and 203 full‐texts were read, of which 69 were included in our review. Several risk and protective factors were encountered including somatic, lifestyle and neuropsychiatric factors, and they are further scrutinized. Eighteen experts named 31 risk and protective factors in the first Delphi study round, of which physical activity, social isolation and hypertension were ranked highest. Results of round two are being collected.ConclusionFindings from the current study will result in an inventory of relevant modifiable risk and protective factors linked with clinical progression in persons with SCD or MCI. Results will serve as the basis for the development and testing of an online dementia risk reduction tool for use in clinical populations with SCD and MCI.

BackgroundModifiable lifestyle factors offer potential to reduce dementia risk, underscoring the need to identify effective behaviour change techniques (BCTs), particularly as the format of interventions change to incorporate more digital solutions. Goal setting is a key BCT that may influence behaviour change for dementia risk reduction (DRR). This study examined whether engagement with goal setting in a digitally delivered intervention was associated with improved DRR behaviours in individuals with subjective cognitive decline (SCD) or mild cognitive impairment (MCI).MethodParticipants with SCD or MCI who completed the intervention arm of the MyCOACH randomised controlled trial (Amos et al., 2023) were included (n = 135, female = 62.2%, Mage = 74.55). A novel framework was developed to evaluate the quality of self‐directed SMART goals from the e‐learning and engagement with practitioner‐led teleconference goal setting were also assessed. A hierarchical regression analysis examined whether engagement with goal setting predicted DRR behaviour change, together with the effects of psychological determinants (attitudes, norms, perceived behavioural control) and baseline dementia risk (low vs. high), while controlling for demographic variables (age, gender, education). Secondary analyses compared the impact of self‐directed versus practitioner‐led goal setting on specific behaviours. Behaviour change was measured as the difference in a modified Australian National University‐Alzheimer's Disease Risk Index score between baseline and immediate follow‐up.ResultEngagement in goal setting alone did not significantly predict behaviour change in this context. Higher baseline dementia risk was the only significant predictor of DRR improvements (β =‐.439, p < .001). Secondary analyses revealed that higher‐quality self‐directed SMART goals were associated with improved MIND diet adherence (β =.024, p =.038), but no associations were found for physical activity behaviours. Practitioner‐led goal setting showed no significant effects.ConclusionFindings indicated that goal setting alone did not significantly predict overall behavioural changes for DRR. However, setting higher‐quality dietary goals may drive changes specific to MIND diet adherence. This underscores the need for future research to explore combining or refining BCTs to determine what works best for different behaviours relevant to DRR. Notably, the impact of goal setting on long‐term outcomes was not assessed here and remains to be explored.

IntroductionDescendants of patients with dementia have a higher risk to develop dementia. This study aims to investigate the uptake and effectiveness of an online tailor-made lifestyle programme for dementia risk...

Dementia risk assessment tools: an update.

Background: To examine the discriminant validity of the Montreal Cognitive Assessment (MoCA) and the Mini-Mental State Examination (MMSE) in detecting patients with cognitive impairment at higher risk for dementia at a memory clinic setting. Methods: Memory clinic patients were administered the MoCA, MMSE, and a comprehensive formal neuropsychological battery. Mild cognitive impairment (MCI) subtypes were dichotomized into two groups: single domain–MCI (sd–MCI) and multiple domain-MCI (md–MCI). Area under the receiver operating characteristic curve (ROC) analysis was used to compare the discriminatory ability of the MoCA and the MMSE. Results: Two hundred thirty patients were recruited, of which 136 (59.1%) were diagnosed with dementia, 61 (26.5%) with MCI, and 33 (14.3%) with no cognitive impairment (NCI). The majority of MCI patients had md–MCI (n= 36, 59%). The MoCA had significantly larger AUCs than the MMSE in discriminating md–MCI from the lower risk group for incident dementia (NCI and sd–MCI) [MoCA 0.92 (95% CI, 0.86– 0.98) vs. MMSE 0.84 (95% CI, 0.75–0.92), p= 0.02). At their optimal cut-off points, the MoCA (19/20) remained superior to the MMSE (23/24) in detecting md–MCI [sensitivity: 0.83 vs. 0.72; specificity: 0.86 vs. 0.83; PPV: 0.79 vs. 0.72; NPV: 0.89 vs. 0.83; correctly classified: 85.1% vs. 78.7%]. Conclusion: The MoCA is superior to the MMSE in the detection of patients with cognitive impairment at higher risk for incident dementia at a memory clinic setting.

BackgroundNearly 1 in 3 older adults are living with mild cognitive impairment (MCI) or subjective cognitive decline (SCD), which places them at increased risk for Alzheimer's disease and related dementias (ADRD). Although multi‐domain interventions may reduce dementia risk, most are time‐intensive and difficult to scale.MethodWe performed a randomized, controlled trial (RCT) comparing 3 brief, online, multi‐domain interventions: 1) Brain Health Academy (BHA: asynchronous educational videos, 30 hours over 3 months); 2) Brain Health Together (BHT: synchronous group education and group mind‐body movement classes + individual brain health coaching, 30 hours over 3 months); 3) Brain Health Together Plus (BHT+: same format as BHT, 45 hours over 6 months). Eligibility criteria were age 55 years or older, English fluency, reside in U.S., self‐report MCI or SCD, and 2 or more dementia risk factors. A blinded assessor measured outcomes at 0, 3, and 6 months (primary: cognitive function [Creyos composite score] and dementia risk [modified Australian National University Alzheimer's Disease Risk Index]; secondary: validated measures of individual risk domains). Net Promoter Scores (NPS) assessed intervention satisfaction (range: ‐100 to 100, higher=better). Linear mixed models estimated standardized effect sizes (ES) for differences between groups and over time.ResultsOf 760 individuals screened, 165 (18%) were eligible, consented, and randomized (55/group). Enrolled participants had a mean (SD) age of 70 (8) years; 74% were female and 28% were non‐White or Hispanic. Groups did not differ significantly at baseline. We observed significant main effects of time for both primary outcomes and most secondary outcomes, suggesting general improvement over time regardless of treatment group (ES range: 0.21 to 0.41). Loneliness declined significantly more with BHT (ES=‐0.34) and BHT+ (ES=‐0.55) than BHA (ES=‐0.01) (p = 0.01). NPS scores were BHA (8), BHT (26), and BHT+ (57).ConclusionBrief, online interventions may help older adults with MCI/SCD improve cognitive function and reduce dementia risk. Synchronous programs that support participant interaction may be needed to improve loneliness. Satisfaction was highest with the longer, synchronous program. Additional studies are needed to determine whether these benefits are maintained over time.

There is very limited data on the prevalence of abnormal cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) and their predictive value for clinical progression in memory clinic patients with subjective cognitive decline (SCD). To assess the frequency of abnormal CSF biomarkers of AD and their predictive value for clinical progression in memory clinic patients with SCD in comparison to patients with mild cognitive impairment (MCI) from the same cohort. We analyzed prospective data from memory clinic patients of the German Competence Network Dementia cohort with a baseline diagnosis of SCD (n = 82) or MCI (n = 134), distinguished by actuarial neuropsychological MCI criteria ("Jak-Bondi criteria"). Risk of clinical progression during 3-year follow-up was evaluated with Cox-Proportional-Hazard models. Prevalence of abnormal values in CSF markers of tau-mediated neurodegeneration (67.8% versus 46.3%) but not of amyloid deposition (40.3% versus 35.4%) was significantly higher in MCI compared to SCD. The rate of incident AD dementia (26.1% versus 12.2%) was also significantly higher in MCI. In SCD, additional 22% progressed to MCI during follow-up. Combined amyloid/tau abnormality was the strongest predictor of clinical progression in both groups. High prevalence of biomarker abnormality and clinical progression, together with the predictive value of CSF biomarkers, in memory clinic patients with SCD support the validity and usefulness of this condition as a "pre-MCI" at risk stage of AD.

Psychological stress has been proposed as a risk factor for cognitive impairment and dementia. However, it remains unclear how an individual's stress-coping ability (i.e., psychological resilience) is related to cognition. This cross-sectional study investigated whether perceived stress and psychological resilience were associated with cognition and a modifiable dementia risk score in a large community-based sample of cognitively normal adults. The moderating effect of psychological resilience was also examined. Participants (mean age = 57 ± 7 years) enrolled in the web-based Healthy Brain Project completed the Perceived Stress Scale and the Connor-Davidson Resilience Scale. Domains of attention and working memory were assessed using the Cogstate Brief Battery (n = 1,709), and associative memory was assessed using the Cambridge Neuropsychological Test Automated Battery (n = 1,522). Dementia risk was estimated for 1,913 participants using a modified version of the Cardiovascular Risk Factors, Aging, and Incidence of Dementia dementia risk score, calculated using only readily modifiable dementia risk factors. In separate linear regression analyses adjusted for age, sex, education, and race, greater levels of perceived stress and lower levels of psychological resilience were associated with poorer performance across all cognitive domains, as well as a higher modifiable dementia risk score. Psychological resilience did not moderate the effect of perceived stress on cognition or the dementia risk score. Higher perceived stress and lower resilience were associated with poorer cognition and a greater burden of modifiable dementia risk factors. Intervention studies are required to determine if lowering stress and building resilience can mitigate cognitive deficits and reduce dementia risk.

Prevalence of mild behavioral impairment in mild cognitive impairment and subjective cognitive decline, and its association with caregiver burden.

Sleep problems are very prevalent in older adults, especially in those at risk for dementia. But the relationships between sleep parameters and subjective or objective cognitive decline are still inconclusive. The study aimed to investigate the self-reported and objectively measured sleep characteristics in older adults with mild cognitive impairment (MCI) and subjective cognitive decline (SCD). This study adopted a cross-sectional design. We included older adults with SCD or MCI. Sleep quality was measured separately by the Pittsburgh sleep quality index (PSQI) and ActiGraph. Participants with SCD were divided into low, moderate, and high levels of SCD groups. Independent samples T-tests, one-way ANOVA, or nonparametric tests were used to compare the sleep parameters across groups. Covariance analyses were also performed to control the covariates. Around half of the participants (45.9%) reported poor sleep quality (PSQI＜7), and 71.3% of participants slept less than 7 hours per night, as measured by ActiGraph. Participants with MCI showed shorter time in bed (TIB) (p＜0.05), a tendency of shorter total sleep time (TST) at night (p = 0.074) and for each 24-hour cycle (p = 0.069), compared to those with SCD. The high SCD group reported the highest PSQI total score and longest sleep latency than all the other three groups (p＜0.05). Both the MCI and high SCD groups had shorter TIB and TST for each 24-hour cycle than the low or moderate SCD groups. Besides, participants with multiple-domain SCD reported poorer sleep quality than those with single-domain SCD (p＜0.05). Sleep dysregulation is prevalent in older adults with a risk for dementia. Our findings revealed that objectively measured sleep duration might be an early sign of MCI. Individuals with high levels of SCD demonstrated poorerself-perceived sleep quality and deserved more attention. Improving sleep quality might be a potential target to prevent cognitive decline for people with a risk for dementia.

P153: The CIMA-Q and CompAS cohort studies on factors associated with Alzheimer's disease (AD): Exploring sociodemographic, health and neuropsychological profile of Subjective Cognitive Decline (SCD) participants from two culturally differentiated samples.

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Subjective cognitive complaints are generally poorly associated with objective memory functioning in older persons. Subjective cognitive decline (SCD) is a key feature in SCD and amnestic mild cognitive impairment (aMCI) which both can represent early Alzheimer's disease (AD). The aim of this study was to assess how memory clinic patients with SCD, MCI and mild AD dementia scored on 3 different complaint measures and if the format of assessment had an impact on the association with cognitive functioning, age, and depressive symptoms. We included 17 SCD patients, 17 aMCI patients, 17 patients with mild AD, and 30 controls. Complaints were assessed with the Cognitive Change Index (CCI), the Subjective Memory Complaints (SMC) scale, and the Memory Complaint Questionnaire (MAC-Q). There were no significant differences between the total scores in the patient groups on the questionnaires. However, significant differences were found in the number of patients classified with impairment when using the CCI, the SMC, and the MAC-Q. Scores on all questionnaires were significantly associated with depressive symptoms, and significant associations with age, gender, and Addenbrookes Cognitive Examination score were found for the SMC. In patients with cognitive dysfunction, lower memory awareness significantly predicted fewer cognitive complaints. SCD patients in a memory clinic setting report the same degree of cognitive impairment as patients with aMCI and mild dementia, and in a hospital-based cohort we extend previous findings from healthy controls, that definition of SCD may depend on the format of assessment.