Interinstrument Reliability Between the Squegg® Smart Dynamometer and Hand Grip Trainer and the Jamar® Hydraulic Hand Dynamometer: A Pilot Study.

IMPORTANCE: Occupational therapists need dependable and accurate instruments for remote assessments and monitoring of hand functionality. These assessments monitor progress, evaluate interventions, and guide independence goals. OBJECTIVE: To assess the interinstrument reliability and concurrent validity of the Squegg® Smart Dynamometer and Hand Grip Trainer and the Jamar® Hydraulic Hand Dynamometer. DESIGN: Repeated-measures design. SETTING: Individual clinic in Bucharest, Romania. PARTICIPANTS: Forty middle-age and older adult volunteers, healthy and free from any neuromuscular, orthopedic dysfunction that affected hand strength. OUTCOMES AND MEASURES: Participants' maximal grip strength (MGS) for both their dominant and nondominant hands was measured with both devices. Participants with odd-numbered IDs were measured with the Squegg first and the Jamar second, and those with even-numbered IDs were measured in opposite sequence. RESULTS: Paired-samples t tests on overall mean MGS and mean MGS (three measures on each hand) showed no statistically significant differences between the two devices. Intraclass correlation analysis showed good to excellent interinstrument agreement. Pearson correlations between measurements across all participants, and hands, indicated strong agreement. CONCLUSIONS AND RELEVANCE: The Squegg shows promise for health care professionals, including occupational therapists, for grip strength assessment in clinical contexts. What This Article Adds: These results offer initial psychometric data for a new remote MGS measurement device. MGS is crucial for assessing the physical function of aging adults. Reliable measurements from such a device are vital for occupational therapists to guide treatment interventions and assess hand function's impact on daily activities.

Masitinib for mild-to-moderate Alzheimer's disease: results from a randomized, placebo-controlled, phase 3, clinical trial.

BACKGROUND: Masitinib is an orally administered tyrosine kinase inhibitor that targets activated cells of the neuroimmune system (mast cells and microglia). Study AB09004 evaluated masitinib as an adjunct to cholinesterase inhibitor and/or memantine in patients with mild-to-moderate dementia due to probable Alzheimer's disease (AD). METHODS: Study AB09004 was a randomized, double-blind, two parallel-group (four-arm), placebo-controlled trial. Patients aged ≥50 years, with clinical diagnosis of mild-to-moderate probable AD and a Mini-Mental State Examination (MMSE) score of 12-25 were randomized (1:1) to receive masitinib 4.5 mg/kg/day (administered orally as two intakes) or placebo. A second, independent parallel group (distinct for statistical analysis and control arm), randomized patients (2:1) to masitinib at an initial dose of 4.5 mg/kg/day for 12 weeks that was then titrated to 6.0 mg/kg/day, or equivalent placebo. Multiple primary outcomes (each tested at a significance level of 2.5%) were least-squares mean change from baseline to week 24 in the Alzheimer's Disease Assessment Scale - cognitive subscale (ADAS-cog), or the Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory scale (ADCS-ADL). Safety for each masitinib dose level was compared against a pooled placebo population. RESULTS: Masitinib (4.5 mg/kg/day) (n=182) showed significant benefit over placebo (n=176) according to the primary endpoint of ADAS-cog, -1.46 (95% CI [-2.46, -0.45]) (representing an overall improvement in cognition) versus 0.69 (95% CI [-0.36, 1.75]) (representing increased cognitive deterioration), respectively, with a significant between-group difference of -2.15 (97.5% CI [-3.48, -0.81]); p<0.001. For the ADCS-ADL primary endpoint, the between-group difference was 1.82 (97.5% CI [-0.15, 3.79]); p=0.038 (i.e., 1.01 (95% CI [-0.48, 2.50]) (representing an overall functional improvement) versus -0.81 (95% CI [-2.36, 0.74]) (representing increased functional deterioration), respectively). Safety was consistent with masitinib's known profile (maculo-papular rash, neutropenia, hypoalbuminemia). Efficacy results from the independent parallel group of titrated masitinib 6.0 mg/kg/day versus placebo (n=186 and 91 patients, respectively) were inconclusive and no new safety signal was observed. CONCLUSIONS: Masitinib (4.5 mg/kg/day) may benefit people with mild-to-moderate AD. A confirmatory study has been initiated to substantiate these data. TRIAL REGISTRATION: EudraCT: 2010-021218-50. CLINICALTRIALS: gov : NCT01872598.

Hypersensitivity reactions to nonsteroidal anti-inflammatory drugs: does age matter?

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are reported to be the leading cause of drug hypersensitivity reactions. The aim of this study was to characterize a cohort of patients with NSAID hypersensitivity and establish if there are any differences between two groups of adult patients, under 55 years old and over 55 years old, and identify safe alternative options. METHODS: Patients with NSAID hypersensitivity who were referred to a single tertiary Allergy center from January 2019 to December 2021 were included. Clinical information was obtained from a review of medical records. RESULTS: A total of 135 patients with a history of NSAID-induced hypersensitivity reactions were included, 80 patients under 55 years old and 55 patients older than 55. Most of the patients enrolled were female (80.74%) and the mean age was 50.21 years, ranging from 18 to 78 years old. The time interval between the first reaction and the allergy work-up was longer in the older group (average timeframe 6.87 years) than in the younger group (average timeframe 3.77 years). The main culprit was metamizole in both groups. An oral provocation test to paracetamol was performed in most of the patients who tolerated the intake of 1000 mg, except for 2 patients who developed angioedema. CONCLUSION: Angioedema was the most encountered symptom in our population. Age does not influence the allergy work-up of patients with a history of NSAID-induced hypersensitivity reactions. The drug provocation challenge remains the gold standard for finding a suitable alternative in patients with NSAID-induced hypersensitivity.

Successful Dabrafenib Desensitization Protocols in a Patient with Metastatic Melanoma.

Dabrafenib and trametinib are two available molecules that have been approved for the treatment of metastatic melanoma with BRAF-V600E or V600K mutations. Their combined therapy has led to long-lasting survival benefits and substantially improved outcomes. Until now, only a few cases of severe hypersensitivity reactions to dabrafenib and vemurafenib have been reported, and even fewer desensitization protocols to these molecules have been documented. We report the case of a 71-year-old female patient with metastatic melanoma harboring a BRAF-V600E mutation undergoing targeted therapy with dabrafenib and trametinib. Two weeks after the initiation of the combined treatment, she developed a hypersensitivity reaction. The cause-effect relationship between dabrafenib and the hypersensitivity reaction was demonstrated twice, when symptoms recurred upon dabrafenib reintroduction. We started a rapid 3-day dabrafenib desensitization protocol, which was well tolerated. When the patient discontinued the drug administration, we decided on a longer protocol that included more steps and more days in order to prevent the occurrence of other hypersensitivity reactions. Our patient tolerated both rapid and slow-going schedules, the first one reaching the final dose within 3 days and the second one reaching the total daily dose within 14 days. Depending on the patient's needs, the severity of the hypersensitivity reaction and the hospital's availability, the doctor may choose either the rapid or slow-going desensitization protocol.

Sulfiredoxin-1 blood mRNA expression levels negatively correlate with hippocampal atrophy and cognitive decline.

Introduction: Cognitive decline, correlating with hippocampal atrophy, characterizes several neurodegenerative disorders having a background of low-level chronic inflammation and oxidative stress. Methods: In this cross-sectional study, we examined how cognitive decline and hippocampal subfields volume are associated with the expression of redox and inflammatory genes in peripheral blood. We analyzed 34 individuals with different cognitive scores according to Mini-Mental State Examination, corrected by age and education (adjMMSE). We identified a group presenting cognitive decline (CD) with adjMMSE<27 (n=14) and a normal cognition (NC) group with adjMMSE≥27 (n=20). A multiparametric approach, comprising structural magnetic resonance imaging measurement of different hippocampal segments and blood mRNA expression of redox and inflammatory genes was applied. Results: Our findings indicate that hippocampal segment volumes correlate positively with adjMMSE and negatively with the blood transcript levels of 19 genes, mostly redox genes correlating especially with the left subiculum and presubiculum. A strong negative correlation between hippocampal subfields atrophy and Sulfiredoxin-1 ( SRXN1) redox gene was emphasized. Conclusions: Concluding, these results suggest that SRXN1 might be a valuable candidate blood biomarker for non-invasively monitoring the evolution of hippocampal atrophy in CD patients.

Alzheimer's disease research progress in the Mediterranean region: The Alzheimer's Association International Conference Satellite Symposium.

As research and services in the Mediterranean region continue to increase, so do opportunities for global collaboration. To support such collaborations, the Alzheimer's Association was due to hold its seventh Alzheimer's Association International Conference Satellite Symposium in Athens, Greece in 2021. Due to the COVID-19 pandemic, the meeting was held virtually, which enabled attendees from around the world to hear about research efforts in Greece and the surrounding Mediterranean countries. Research updates spanned understanding the biology of, treatments for, and care of people with Alzheimer's disease (AD_ and other dementias. Researchers in the Mediterranean region have outlined the local epidemiology of AD and dementia, and have identified regional populations that may expedite genetic studies. Development of biomarkers is expected to aid early and accurate diagnosis. Numerous efforts have been made to develop culturally specific interventions to both reduce risk of dementia, and to improve quality of life for people living with dementia.

Omalizumab for successful chemotherapy desensitisation: What we know so far.

BACKGROUND: Hypersensitivity reactions induced by chemotherapeutic drugs may influence the course of the oncologic disease by preventing doctors from prescribing first-line therapy. In order to prevent another hypersensitivity reaction to the culprit chemotherapeutic agent, the physician can decide between two possibilities: premedication or desensitisation protocols. Rapid drug desensitisation showed successful results for most patients, but some of them may develop symptoms. Although omalizumab is not licensed as premedication or adjuvant therapy in chemotherapy desensitisation protocols, there have been published some case reports and small sample size studies that indicated promising results. METHODS: We reviewed all the published literature regarding the use of omalizumab during chemotherapy desensitisation protocols. RESULTS AND CONCLUSIONS: We found a great heterogeneity between the doses and the interval between omalizumab injections and chemotherapy - rapid drug desensitisation, but most of the studies showed promising results. As a corollary, we propose a dose regimen of omalizumab administered before the first desensitisation protocol. Then, omalizumab should be administered one day before every chemotherapy regimen. Omalizumab might be used as an adjuvant therapy and might be a solution for a hopeless situation.

Drug Provocation Testing in the Diagnosis of Symmetrical Drug-Related Intertriginous and Flexural Exanthema (SDRIFE) Induced by Clarithromycin.

Introduction: Hypersensitivity reactions to macrolides are rarely described in the literature wherefore they are considered one of the safest choices for antibiotic treatment. Out of the reported reactions, cutaneous manifestations have the highest frequency, particularly non-immediate ones. Materials and methods: We report a case of a 71-year-old female who was referred to us for the drug allergy work-up of a rash unaccompanied by systemic signs, compatible with symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) induced by clarithromycin. Results: The diagnosis was confirmed by a drug provocation test, which reproduced the index reaction. Discussion: As SDRIFE is quite infrequent, it can easily be misdiagnosed if the patient cannot present a clear history of the index reaction or the causal connection with the incriminated drug is not clear. Despite the fact that macrolides rarely induce hypersensitivity reactions, they must not be overlooked in the assessment of a drug induced reaction, as they are a potential etiological factor.

Distinctive Under-Expression Profile of Inflammatory and Redox Genes in the Blood of Elderly Patients with Cardiovascular Disease.

PURPOSE: Chronic low-grade inflammation and oxidative stress are present in most of the pathologic mechanisms underlying non-communicable diseases. Inflammation and redox biomarkers might therefore have a value in disease prognosis and therapy response. In this context, we performed a case-control study for assessing in whole blood the expression profile of inflammation and redox-related genes in elderly subjects with various comorbidities. PATIENTS AND METHODS: In the blood of 130 elderly subjects with various pathologies (cardiovascular disease, hypertension, dyslipidemia including hypercholesterolemia, type 2 diabetes mellitus), kept under control by polyvalent disease-specific medication, we investigated by pathway-focused qRT-PCR a panel comprising 84 inflammation-related and 84 redox-related genes. RESULTS: The study highlights a distinctive expression profile of genes critically involved in NF-κB-mediated inflammation and redox signaling in the blood of patients with cardiovascular disease, characterized by significant down-regulation of the genes NFKB2, NFKBIA, RELA, RELB, AKT1, IRF1, STAT1, CD40, LTA, TRAF2, PTGS1, ALOX12, DUOX1, DUOX2, MPO, GSR, TXNRD2, HSPA1A, MSRA, and PDLIM1. This gene expression profile defines the transcriptional status of blood leukocytes in stable disease under medication control, without discriminating between disease- and therapy-related changes. CONCLUSION: The study brings preliminary proof on a minimally invasive strategy for monitoring disease in patients with cardiovascular pathology, from the point of view of inflammation or redox dysregulation in whole blood.

Biomarker counseling, disclosure of diagnosis and follow-up in patients with mild cognitive impairment: A European Alzheimer's disease consortium survey.

OBJECTIVES: Mild cognitive impairment (MCI) is associated with an increased risk of further cognitive decline, partly depending on demographics and biomarker status. The aim of the present study was to survey the clinical practices of physicians in terms of biomarker counseling, management, and follow-up in European expert centers diagnosing patients with MCI. METHODS: An online email survey was distributed to physicians affiliated with European Alzheimer's disease Consortium centers (Northern Europe: 10 centers; Eastern and Central Europe: 9 centers; and Southern Europe: 15 centers) with questions on attitudes toward biomarkers and biomarker counseling in MCI and dementia. This included postbiomarker counseling and the process of diagnostic disclosure of MCI, as well as treatment and follow-up in MCI. RESULTS: The response rate for the survey was 80.9% (34 of 42 centers) across 20 countries. A large majority of physicians had access to biomarkers and found them useful. Pre- and postbiomarker counseling varied across centers, as did practices for referral to support groups and advice on preventive strategies. Less than half reported discussing driving and advance care planning with patients with MCI. CONCLUSIONS: The variability in clinical practices across centers calls for better biomarker counseling and better training to improve communication skills. Future initiatives should address the importance of communicating preventive strategies and advance planning.

Biomarker-based prognosis for people with mild cognitive impairment (ABIDE): a modelling study.

BACKGROUND: Biomarker-based risk predictions of dementia in people with mild cognitive impairment are highly relevant for care planning and to select patients for treatment when disease-modifying drugs become available. We aimed to establish robust prediction models of disease progression in people at risk of dementia. METHODS: In this modelling study, we included people with mild cognitive impairment (MCI) from single-centre and multicentre cohorts in Europe and North America: the European Medical Information Framework for Alzheimer's Disease (EMIF-AD; n=883), Alzheimer's Disease Neuroimaging Initiative (ADNI; n=829), Amsterdam Dementia Cohort (ADC; n=666), and the Swedish BioFINDER study (n=233). Inclusion criteria were a baseline diagnosis of MCI, at least 6 months of follow-up, and availability of a baseline Mini-Mental State Examination (MMSE) and MRI or CSF biomarker assessment. The primary endpoint was clinical progression to any type of dementia. We evaluated performance of previously developed risk prediction models-a demographics model, a hippocampal volume model, and a CSF biomarkers model-by evaluating them across cohorts, incorporating different biomarker measurement methods, and determining prognostic performance with Harrell's C statistic. We then updated the models by re-estimating parameters with and without centre-specific effects and evaluated model calibration by comparing observed and expected survival. Finally, we constructed a model combining markers for amyloid deposition, tauopathy, and neurodegeneration (ATN), in accordance with the National Institute on Aging and Alzheimer's Association research framework. FINDINGS: We included all 2611 individuals with MCI in the four cohorts, 1007 (39%) of whom progressed to dementia. The validated demographics model (Harrell's C 0·62, 95% CI 0·59-0·65), validated hippocampal volume model (0·67, 0·62-0·72), and updated CSF biomarkers model (0·72, 0·68-0·74) had adequate prognostic performance across cohorts and were well calibrated. The newly constructed ATN model had the highest performance (0·74, 0·71-0·76). INTERPRETATION: We generated risk models that are robust across cohorts, which adds to their potential clinical applicability. The models could aid clinicians in the interpretation of CSF biomarker and hippocampal volume results in individuals with MCI, and help research and clinical settings to prepare for a future of precision medicine in Alzheimer's disease. Future research should focus on the clinical utility of the models, particularly if their use affects participants' understanding, emotional wellbeing, and behaviour. FUNDING: ZonMW-Memorabel.

Methodology for assessing end-user requirements in the Ella4Life project: elders' perspectives about self-monitoring.

The purpose of this paper is to explore elders' perspectives about self-monitoring and using specially developed sensor technology for measuring health indicators. The qualitative research method is focus-groups with guidelines that were designed for understanding elder's requirements about monitoring health indicators. We present them two devices: the first sensor is a device for monitoring of cardiac action potential fixed into an armchair, the second sensor for monitoring vital signs is placed in a bathtub. The people express their needs and expectations regarding the idea of having sensors for monitoring health indicators and body movement in their own house.

Association Between Later Life Lifestyle Factors and Alzheimer's Disease Biomarkers in Non-Demented Individuals: A Longitudinal Descriptive Cohort Study.

BACKGROUND: Lifestyle factors have been associated with the risk of dementia, but the association with Alzheimer's disease (AD) remains unclear. OBJECTIVE: To examine the association between later life lifestyle factors and AD biomarkers (i.e., amyloid-ß 1-42 (Aß42) and tau in cerebrospinal fluid (CSF), and hippocampal volume) in individuals with subjective cognitive decline (SCD) and mild cognitive impairment (MCI). In addition, to examine the effect of later life lifestyle factors on developing AD-type dementia in individuals with MCI. METHODS: We selected individuals with SCD (n = 111) and MCI (n = 353) from the DESCRIPA and Kuopio Longitudinal MCI studies. CSF Aß42 and tau concentrations were assessed with ELISA assay and hippocampal volume with multi-atlas segmentation. Lifestyle was assessed by clinical interview at baseline for: social activity, physical activity, cognitive activity, smoking, alcohol consumption, and sleep. We performed logistic and Cox regression analyses adjusted for study site, age, gender, education, and diagnosis. Prediction for AD-type dementia was performed in individuals with MCI only. RESULTS: Later life lifestyle factors were not associated with AD biomarkers or with conversion to AD-type dementia. AD biomarkers were strongly associated with conversion to AD-type dementia, but these relations were not modulated by lifestyle factors. Apolipoprotein E (APOE) genotype did not influence the results. CONCLUSIONS: Later life lifestyle factors had no impact on key AD biomarkers in individuals with SCD and MCI or on conversion to AD-type dementia in MCI.

The impact of automated hippocampal volumetry on diagnostic confidence in patients with suspected Alzheimer's disease: A European Alzheimer's Disease Consortium study.

INTRODUCTION: Hippocampal volume is a core biomarker of Alzheimer's disease (AD). However, its contribution over the standard diagnostic workup is unclear. METHODS: Three hundred fifty-six patients, under clinical evaluation for cognitive impairment, with suspected AD and Mini-Mental State Examination ≥20, were recruited across 17 European memory clinics. After the traditional diagnostic workup, diagnostic confidence of AD pathology (DCAD) was estimated by the physicians in charge. The latter were provided with the results of automated hippocampal volumetry in standardized format and DCAD was reassessed. RESULTS: An increment of one interquartile range in hippocampal volume was associated with a mean change of DCAD of -8.0% (95% credible interval: [-11.5, -5.0]). Automated hippocampal volumetry showed a statistically significant impact on DCAD beyond the contributions of neuropsychology, 18F-fluorodeoxyglucose positron emission tomography/single-photon emission computed tomography, and cerebrospinal fluid markers (-8.5, CrI: [-11.5, -5.6]; -14.1, CrI: [-19.3, -8.8]; -10.6, CrI: [-14.6, -6.1], respectively). DISCUSSION: There is a measurable effect of hippocampal volume on DCAD even when used on top of the traditional diagnostic workup.

MCI Patients in Europe: Medication and Comorbidities. The DESCRIPA Study.

OBJECTIVES: The main objective of the present study was to investigate the prevalence and type of medication taken by MCI patients in the DECRIPA cohort. A secondary objective was to assess the cognitive function of these patients and the relationship between the results of neuropsychometric tests and medication use. MATERIALS AND METHODS: We selected 880 subjects (375 males, 505 females) who were older than 55 years without obvious causes of cognitive impairment. A complete history was obtained for all patients. In addition, demographical data were collected and several factors were studied, including the types and dosages of the medications taken. Comparisons between groups were statistically analyzed in relation to the number of medications. RESULTS: Most patients (85.7%, n=754) were taking at least one medication during the study period. The median (interquartile range-IQ) number of medications per participant was 3 (1-5), whereas 40% of the patients took at least 4 medications. The types of medications that were most often taken were cardiovascular drugs (62.0%), antidepressants (16.8%), sedatives (14.6%), thyroid drugs (10.0%) and anti-diabetic drugs (7.6%). CONCLUSION: On average, MCI patients take three medications for the prevention or treatment of an average of two medical conditions. The most prevalent types of medications were cardiovascular drugs, antidepressants, sedatives and thyroid drugs. Significant differences in the number of medications taken were observed for gender and age.

DNMT3A moderates cognitive decline in subjects with mild cognitive impairment: replicated evidence from two mild cognitive impairment cohorts.

Epigenetic dysregulation has been associated with cognitive decline and Alzheimer's disease. The present study investigated associations between common SNPs in genes regulating DNA methylation and age-related changes in cognitive decline in two independent prospective cohorts of patients suffering from mild cognitive impairment. An association between the rs1187120 SNP in DNMT3A and annual decline in cognitive functioning was discovered and replicated, suggesting that DNMT3A moderates cognitive decline in subjects with mild cognitive impairment.

Single-domain amnestic mild cognitive impairment identified by cluster analysis predicts Alzheimer's disease in the european prospective DESCRIPA study.

BACKGROUND/AIMS: To identify prodromal Alzheimer's disease (AD) subjects using a data-driven approach to determine cognitive profiles in mild cognitive impairment (MCI). METHODS: A total of 881 MCI subjects were recruited from 20 memory clinics and followed for up to 5 years. Outcome measures included cognitive variables, conversion to AD, and biomarkers (e.g. CSF, and MRI markers). Two hierarchical cluster analyses (HCA) were performed to identify clusters of subjects with distinct cognitive profiles. The first HCA included all subjects with complete cognitive data, whereas the second one selected subjects with very mild MCI (MMSE ≥28). ANOVAs and ANCOVAs were computed to examine whether the clusters differed with regard to conversion to AD, and to AD-specific biomarkers. RESULTS: The HCAs identified 4-cluster solutions that best reflected the sample structure. One cluster (aMCIsingle) had a significantly higher conversion rate (19%), compared to subjective cognitive impairment (SCI, p < 0.0001), and non-amnestic MCI (naMCI, p = 0.012). This cluster was the only one showing a significantly different biomarker profile (Aß42, t-tau, APOE ε4, and medial temporal atrophy), compared to SCI or naMCI. CONCLUSION: In subjects with mild MCI, the single-domain amnestic MCI profile was associated with the highest risk of conversion, even if memory impairment did not necessarily cross specific cut-off points. A cognitive profile characterized by isolated memory deficits may be sufficient to warrant applying prevention strategies in MCI, whether or not memory performance lies below specific z-scores. This is supported by our preliminary biomarker analyses. However, further analyses with bigger samples are needed to corroborate these findings.

The association between APOE ε4 and Alzheimer-type dementia among memory clinic patients is confined to those with a higher education. The DESCRIPA Study.

We assessed the interaction between the APOE ε4 allele and education level in the etiology of Alzheimer's disease (AD) among memory clinic patients from the multicenter DESCRIPA study. Subjects (n = 544) were followed for 1 to 5 years. We used Cox's stratified survival modeling, adjusted for age, gender, and center. APOE ε4 predicted the onset of AD-type dementia in middle (HR 3.45 95% CI 1.79-6.65, n = 222) and high (HR 3.67 95% CI 1.36-9.89, n = 139) but not in low educated subjects (HR 0.81, 95% CI 0.38-1.72, n = 183). This suggests that mechanisms in developing Alzheimer-type dementia may differ between educational groups that raises questions related to Alzheimer-type dementia prevention.

Do instrumental activities of daily living predict dementia at 1- and 2-year follow-up? Findings from the Development of Screening guidelines and diagnostic Criteria for Predementia Alzheimer's disease study.

OBJECTIVES: To investigate whether problems in instrumental activities of daily living (IADL) can add to conventionally used clinical measurements in helping to predict a diagnosis of dementia at 1- and 2-year follow-up. DESIGN: Multicenter prospective cohort study. SETTING: Memory clinics in Europe. PARTICIPANTS: Individuals aged 55 and older without dementia. MEASUREMENTS: IADLs were measured using pooled activities from five informant-based questionnaires. Structural equation modeling (SEM) was used to investigate the relation between IADLs and dementia. Age, sex, education, depression, and cognitive measures (Mini-Mental State Examination and verbal memory) were included in the model. RESULTS: Five hundred thirty-one participants had baseline and 1-year follow-up assessments; 69 (13.0%) of these had developed dementia at 1-year follow-up. At 2-year follow-up, 481 participants were seen, of whom 100 (20.8%) had developed dementia. Participants with IADL disabilities at baseline had a higher conversion rate (24.4%) than participants without IADL disabilities (16.7%) (chi-square = 4.28, degrees of freedom = 1, P = .04). SEM showed that IADL disability could help predict dementia in addition to the measured variables at 1-year follow-up (odds ratio (OR) = 2.20, 95% confidence interval (CI) = 1.51-3.13) and 2-year follow-up (OR = 2.11, 95% CI = 1.33-3.33). CONCLUSION: IADL disability is a useful addition to the diagnostic process in a memory clinic setting, indicating who is at higher risk of developing dementia at 1- and 2-year follow-up.