Cambridge Cognitive Examination Research Articles

1. Validity and reliability of CAMCOG‐DS2 and other cognitive outcomes measures for clinical trials of AD in DS

AbstractBackgroundDown syndrome (DS) is an important population to include in clinical trials aiming to prevent or delay Alzheimer’s disease (AD). This talk will summarise previous work in trajectory modelling to identify the earliest ages of change in cognition and the optimal sample sizes needed for clinical trials in DS. It will present validate data on the new version of the Cambridge Cognitive Examination–Down syndrome version II (CAMCOG‐DS‐II) alongside established cognitive tests. The CAMCOG‐DS‐II has been developed to assess cognitive impairments associated with dementia in people with DS.MethodThis was an observational, multicentre, longitudinal study (n = 174) across seven existing cohorts in six different European languages to validate cognitive tests in adults with DS aged 25 years and older. It assessed the relationships between tests of cognition, behaviour, function, and health. Cognitive assessments included the CAMCOG‐DS‐II, the CANTAB Paired Associates Learning (PAL) Task, the modified Cued Recall Test (mCRT) and the Purdue Pegboard Test. We examined correlations between tests, group differences between those with and without dementia and explored test‐retest reliability of the CAMCOG‐DS‐II.ResultOur results showed that completion rates for the CAMCOG‐DS‐II were high, and floor and ceiling effects were low. The CAMCOG‐DS‐II memory sub‐score correlated significantly with the mCRT total recall score (Spearman’s ∼0.5), and the praxis sub‐score significantly correlated with the Purdue Pegboard total score (Spearman’s >0.7).ConclusionThere is currently a critical lack of suitable diagnostic and outcome measures that can be used in clinical trials. These results show that the CAMCOG‐DS‐II is a feasible test of cognition and will help to provide sensitive cognitive endpoints for clinical trials which are seeking to find suitable treatments for AD in adults with DS. Future analysis will include trajectories of change from baseline to one year of follow up for each primary outcome measure.

Associations of Gait and Cognitive Impairment and Dementia in Individuals with Down Syndrome

AbstractBackgroundLife expectancy of individuals with Down syndrome (DS) has increased considerably over the years. Atypical aging in Down syndrome (DS) is associated with neuropathological characteristics consistent with Alzheimer disease (AD). Significant gait alterations are associated with an increased risk of dementia for the general population. The aim of this study was to determine whether gait performance is associated with cognitive performance and dementia in adults with DS.MethodThis study included 66 individuals with DS over 20 years of age, divided into three diagnostic groups: stable cognition, prodromal dementia, and dementia. They were evaluated with the Performance‐Oriented Mobility Assessment (POMA), Timed Up and Go test, and Cambridge Examination for Mental Disorders of Older People with Down’s Syndrome and Others with Intellectual Disabilities (CAMDEX‐DS), which includes the Cambridge Cognitive Examination (CAMCOG). Logistic regression model was used to assess the effects of gait and balance on the diagnosis (prodromal dementia and dementia versus stable cognition) adjusting for age, sex, body mass index (BMI), degree of intellectual disability and physical inactivity.ResultThe score on the POMA‐Gait subscale score and body mass index (BMI) were found to be independent predictors of prodromal dementia and dementia (Poma‐Gait OR = 0.67, 0.53‐0.85 CI, p<0.001; and BMI OR = 1.12, 1.021.24 CI, p<0.001). A lower POMA‐Total score indicates a higher fall risk. With the exception of perception, all cognitive domains correlated with the POMA total score (P<0.05).ConclusionThese data indicate that poor gait performance, as assessed by the POMA, as well as a high BMI, were associated with a diagnosis of prodromal dementia or dementia. In those individuals, applying the POMA could facilitate the early diagnosis of dementia, help identify fall risks, and promote the adoption of geriatric interventions focused on improving functional mobility. There is a need for longitudinal studies to characterize the true nature of the associations found, to validate gait instruments specifics to this population, and for future analyses in order to clarify the role that gait and balance play in cognitive decline and the development of dementia.

24 Individual Differences in CAMCOG-DS Performance in Children and Adults with Down's Syndrome and Relationship to Language and Reasoning

Objective:The Cambridge Cognitive Examination for Down's Syndrome (CAMCOG-DS) was developed to assess cognitive functioning and dementia-related cognitive decline in people with Down's Syndrome (DS). It has been translated into different languages and is often used in international studies. Although adapted for people with intellectual disabilities (ID), many tasks involve verbal responses and instructions are presented orally. Therefore, the administration for people with severe language deficits can be challenging. The aim of this retrospective data analysis is to examine the influence of language ability and reasoning on CAMCOG-DS performance. Study 1 examined the relationship between CAMCOG-DS, picture naming, single word comprehension and reasoning in adults with DS. Study 2 replicates and broadens the findings in a sample of children and adults with DS.Participants and Methods:Study 1 included 40 adults with DS between 18 and 51 years (M = 28.6, SD = 8.4). 25 had a mild and 15 a moderate ID. CAMCOG-DS, the short form of the Boston Naming test (BNT), a test for single word comprehension from the Werdenfelser Testbatterie (WTB) and the Colored Progressive Matrices (CPM) were administered. Study 2 included 38 participants between 8 and 59 years (23 children, M = 11.4; 15 adults; M = 31.3). 3 had a borderline, 23 a mild, and 12 a moderate ID. The same tasks as in Study 1 were applied, but the CPM was replaced by its successor, the Raven's 2.Results:In Study 1, participants with mild ID performed better in all tasks than those with moderate ID (p < .05). Moderate relationships were found between CAMCOG-DS total score and the language tasks (r = .56 and r = .46), which remained significant when level of ID was controlled for. There was also a moderate relationship between CAMCOG-DS and reasoning (r = .46). Regression analysis showed that BNT performance predicted CAMCOG-DS performance (R2 = .31). In Study 2, those with mild ID, compared to those with moderate ID, performed better in all tasks (p < .05), however, regarding the CAMCOG-DS and language tasks, this effect was larger in adults than in children. Adults performed better than children in the CAMCOG-DS and BNT (p < .05), but not in single word comprehension or reasoning. As in Study 1, moderate to large correlations were revealed between CAMCOG-DS and language tasks and between CAMCOG-DS and reasoning (r > .52), remaining significant when age and ID level were controlled for. Regression analysis showed that both naming and reasoning but not single word comprehension or age predicted CAMCOG-DS performance (R2 = .69), however, performance was best predicted by naming (R2 = .65).Conclusions:Our results suggest that language ability and reasoning relate to CAMCOG-DS performance, which is best predicted by BNT picture naming. This should be considered in CAMCOG-DS interpretation, as the capabilities of patients with lesser language ability might be underestimated. Future developments of dementia assessments for people with ID should include more nonverbal tasks.

Association of biological sex with clinical outcomes and biomarkers of Alzheimer's disease in adults with Down syndrome.

The study of sex differences in Alzheimer's disease is increasingly recognized as a key priority in research and clinical development. People with Down syndrome represent the largest population with a genetic link to Alzheimer's disease (>90% in the 7th decade). Yet, sex differences in Alzheimer's disease manifestations have not been fully investigated in these individuals, who are key candidates for preventive clinical trials. In this double-centre, cross-sectional study of 628 adults with Down syndrome [46% female, 44.4 (34.6; 50.7) years], we compared Alzheimer's disease prevalence, as well as cognitive outcomes and AT(N) biomarkers across age and sex. Participants were recruited from a population-based health plan in Barcelona, Spain, and from a convenience sample recruited via services for people with intellectual disabilities in England and Scotland. They underwent assessment with the Cambridge Cognitive Examination for Older Adults with Down Syndrome, modified cued recall test and determinations of brain amyloidosis (CSF amyloid-β 42 / 40 and amyloid-PET), tau pathology (CSF and plasma phosphorylated-tau181) and neurodegeneration biomarkers (CSF and plasma neurofilament light, total-tau, fluorodeoxyglucose-PET and MRI). We used within-group locally estimated scatterplot smoothing models to compare the trajectory of biomarker changes with age in females versus males, as well as by apolipoprotein ɛ4 carriership. Our work revealed similar prevalence, age at diagnosis and Cambridge Cognitive Examination for Older Adults with Down Syndrome scores by sex, but males showed lower modified cued recall test scores from age 45 compared with females. AT(N) biomarkers were comparable in males and females. When considering apolipoprotein ɛ4, female ɛ4 carriers showed a 3-year earlier age at diagnosis compared with female non-carriers (50.5 versus 53.2 years, P = 0.01). This difference was not seen in males (52.2 versus 52.5 years, P = 0.76). Our exploratory analyses considering sex, apolipoprotein ɛ4 and biomarkers showed that female ɛ4 carriers tended to exhibit lower CSF amyloid-β 42/amyloid-β 40 ratios and lower hippocampal volume compared with females without this allele, in line with the clinical difference. This work showed that biological sex did not influence clinical and biomarker profiles of Alzheimer's disease in adults with Down syndrome. Consideration of apolipoprotein ɛ4 haplotype, particularly in females, may be important for clinical research and clinical trials that consider this population. Accounting for, reporting and publishing sex-stratified data, even when no sex differences are found, is central to helping advance precision medicine.

Longitudinal Clinical and Cognitive Changes Along the Alzheimer Disease Continuum in Down Syndrome

Alzheimer disease (AD) is the main medical problem in adults with Down syndrome (DS). However, the associations of age, intellectual disability (ID), and clinical status with progression and longitudinal cognitive decline have not been established. To examine clinical progression along the AD continuum and its related cognitive decline and to explore the presence of practice effects and floor effects with repeated assessments. This is a single-center cohort study of adults (aged >18 years) with DS with different ID levels and at least 6 months of follow-up between November 2012 and December 2021. The data are from a population-based health plan designed to screen for AD in adults with DS in Catalonia, Spain. Individuals were classified as being asymptomatic, having prodromal AD, or having AD dementia. Neurological and neuropsychological assessments. The main outcome was clinical change along the AD continuum. Cognitive decline was measured by the Cambridge Cognitive Examination for Older Adults With Down Syndrome and the modified Cued Recall Test. A total of 632 adults with DS (mean [SD] age, 42.6 [11.4] years; 292 women [46.2%]) with 2847 evaluations (mean [SD] follow-up, 28.8 [18.7] months) were assessed. At baseline, there were 436 asymptomatic individuals, 69 patients with prodromal AD, and 127 with AD dementia. After 5 years of follow-up, 17.1% (95% CI, 12.5%-21.5%) of asymptomatic individuals progressed to symptomatic AD in an age-dependent manner (0.6% [95% CI, 0%-1.8%] for age <40 years; 21.1% [95% CI, 8.0%-32.5%] for age 40-44 years; 41.4% [95% CI, 23.1%-55.3%] for age 45-49 years; 57.5% [95% CI, 38.2%-70.8%] for age ≥50 years; P < .001), and 94.1% (95% CI, 84.6%-98.0%) of patients with prodromal AD progressed to dementia with no age dependency. Cognitive decline in the older individuals was most common among those who progressed to symptomatic AD and symptomatic individuals themselves. Importantly, individuals with mild and moderate ID had no differences in longitudinal cognitive decline despite having different performance at baseline. This study also found practice and floor effects, which obscured the assessment of longitudinal cognitive decline. This study found an association between the development of symptomatic AD and a high risk of progressive cognitive decline among patients with DS. These results support the need for population health plans to screen for AD-related cognitive decline from the fourth decade of life and provide important longitudinal data to inform clinical trials in adults with DS to prevent AD.

Trajectories of cognitive change following stroke: stepwise decline towards dementia in the elderly.

Stroke events increase the risk of developing dementia, 10% for a first-ever stroke and 30% for recurrent strokes. However, the effects of stroke on global cognition, leading up to dementia, remain poorly understood. We investigated: (i) post-stroke trajectories of cognitive change, (ii) trajectories of cognitive decline in those who develop dementia over periods of follow-up length and (iii) risk factors precipitating the onset of dementia. Prospective cohort of hospital-based stroke survivors in North-East England was followed for up to 12 years. In this study, we included 355 stroke survivors of ≥75 years of age, not demented 3 months post-stroke, who had had annual assessments during follow-up. Global cognition was measured annually and characterized using standardized tests: Cambridge Cognition Examination—Revised and Mini-Mental State Examination. Demographic data and risk factors were recorded at baseline. Mixed-effects models were used to study trajectories in global cognition, and logistic models to test associations between the onset of dementia and key risk factors, adjusted for age and sex. Of the 355 participants, 91 (25.6%) developed dementia during follow-up. The dementia group had a sharper decline in Cambridge Cognition Examination—Revised (coeff. = −1.91, 95% confidence interval = −2.23 to −1.59, P < 0.01) and Mini-Mental State Examination (coeff. = −0.46, 95% confidence interval = −0.58 to −0.34, P < 0.01) scores during follow-up. Stroke survivors who developed dementia within 3 years after stroke showed a steep decline in global cognition. However, a period of cognitive stability after stroke lasting 3 years was identified for individuals diagnosed with dementia in 4–6 years (coeff. = 0.28, 95% confidence interval = −3.28 to 3.8, P = 0.88) of 4 years when diagnosed at 7–9 years (coeff. = −3.00, 95% confidence interval = −6.45 to 0.45, P = 0.09); and of 6 years when diagnosed at 10–12 years (coeff. = −6.50, 95% confidence interval = −13.27 to 0.27, P = 0.06). These groups then showed a steep decline in Cambridge Cognition Examination—Revised in the 3 years prior to diagnosis of dementia. Risk factors for dementia within 3 years include recurrent stroke (odds ratio = 3.99, 95% confidence interval = 1.30–12.25, P = 0.016) and previous disabling stroke, total number of risk factors for dementia (odds ratio = 2.02, 95% confidence interval = 1.26–3.25, P = 0.004) and a Cambridge Cognition Examination—Revised score below 80 at baseline (odds ratio = 3.50, 95% confidence interval = 1.29–9.49, P = 0.014). Our unique longitudinal study showed cognitive decline following stroke occurs in two stages, a period of cognitive stability followed by rapid decline before a diagnosis of dementia. This pattern suggests stroke may predispose survivors for dementia by diminishing cognitive reserve but with a smaller impact on cognitive function, where cognitive decline may be precipitated by subsequent events, e.g. another cerebrovascular event. This supports the assertion that the development of vascular dementia can be stepwise even when patients have small stroke lesions.

The Effectiveness of GRADIOR: A Neuropsychological Rehabilitation Program for People with Mild Cognitive Impairment and Mild Dementia. Results of a Randomized Controlled Trial After 4 and 12 Months of Treatment.

Background: Computer-based cognitive training programs have been developed with promising results on the maintenance/improvement of cognitive performance in people with dementia.Objective: The objective was to evaluate the effectiveness of the cognitive rehabilitation program “GRADIOR” in people with mild cognitive impairment and mild dementia.Method: This study was a single-blind multicenter randomized clinical trial. Participants were recruited from hospitals/day centers. The experimental group (EG) and control group (CG) received computer-based cognitive training (CCT) and routine daily care, respectively. Outcome measures at T0: baseline, T1: at 4 months, T2: at 12 months were compared within and between-groups.Results: Significant differences or important effect sizes were detected at the intragroup and intergroup level for most variables, observing a trend of improvement and/or maintenance at 4 months by Visual Reasoning of Cambridge Cognitive Examination (CAMCOG), Digit and Arithmetic of WAIS-III, Semantic Verbal Fluency, Mini-Mental State Exam (MMSE), Trail Making Test (TMT)-A-Mistakes and at 12 months by Visual Reasoning of CAMCOG, Digit Symbol of WAIS-III, TMT-B-mistakes, Visual Memory of Rivermead Behavioural Memory Test, Lexical Verbal Fluency-P, Yesavage’s Geriatric Depression Scale (GDS), TMT-A-time scales whose objective was to evaluate some executive functions and/or the memory. The CG presented a worsening trend for most of the measures towards 12 months. There was also a significant interaction between “time and group” for MMSE (F = 8.971; p = 0.03; η2 = 0.019) and the GDS (F = 3.414; p = 0.04; η2 = 0.041), as well as small effect sizes for TMT-A-time (F = 1.641; p = 0.21; η2 = 0.021) and TMT-A-mistakes (F = 0.908; p = 0.41; η2 = 0.019).Conclusion: CCT with GRADIOR has been proved to benefit cognitive functions (ISRCTN:15742788).

Basal ganglia calcifications: No association with cognitive function

Background and purposeBasal ganglia calcifications (BGC), a form of vascular calcification, are a common brain computed tomography (CT) finding. We investigated whether BGC are associated with cognitive function and examined the association between vascular risk factors and BGC. Material and methodsPatients who visited a memory clinic of a Dutch general hospital between April 2009 and April 2015 were included. The patients underwent a standard diagnostic work up including cognitive tests (Cambridge Cognitive Examination, including the Mini Mental State Examination) and brain CT. Vascular risk factors such as hypertension, diabetes mellitus, hyperlipidemia and smoking were assessed. CTs were analyzed for presence and severity (absent, mild, moderate or severe) of BGC. Multivariable logistic regression was used to identify risk factors for BGC and linear regression for the association between BGC and cognitive function. ResultsOf the 1992 patients, 40.3% was male. The median age was 80 years and 866 patients (43.5%) had BGC. BGC was associated with female gender (odds ratio (OR) 1.27, 95% confidence interval (CI) 1.06–1.53, p 0.011), and inversely associated with hypertension (OR 0.74, 95% CI 0.60–0.89, p 0.002) and use of antihypertensive drugs (OR 0.79, 95% CI 0.64–0.98, p 0.031). No association was found between presence and severity of BGC and cognitive function or other vascular risk factors. ConclusionsNo association with cognitive function was found. Risk factors for BGC were female gender, while hypertension and antihypertensive drug use were associated with a lower risk of BGC.

A multimodal study on the effect of sex on Alzheimer's disease clinical and biomarker changes in adults with Down syndrome

AbstractBackgroundThe study of sex differences in Alzheimer's disease (AD) is gaining increasing attention. Yet, few studies have examined the effect of sex in genetically determined forms of AD. Here, we explored the impact of sex on AD‐related clinical and biomarker changes in a population‐based cohort of adults with Down syndrome, who have a lifetime risk of over 90% to develop AD.MethodThis is a cross‐sectional study of 549 adults with Down syndrome. We compared AD prevalence, as well as cognitive and AD biomarker changes, in relation to age and sex in the whole cohort. Participants underwent neuropsychological examination with the Cambridge Cognitive Examination for Older Adults with Down Syndrome (CAMCOG‐DS) and modified cued recall test (mCRT). Most also had at least one biomarker assessment of amyloid pathology (CSF Aβ42, Aβ42/40 ratio and amyloid‐PET), tau (CSF and plasma p‐Tau‐181) and neurodegeneration (CSF and plasma NfL, FDG‐PET and 3T structural MRI). We used within‐group locally estimated scatterplot smoothing (LOESS) models to compare the trajectory of biomarker changes with age in women versus men, as well as the interaction with the APOE ε4 allele.ResultThe prevalence of AD across five‐year age intervals and the mean age at AD diagnosis was similar between men and women. Men and women had similar trajectories in CAMCOG scores with age, but men showed lower mCRT scores from age 45 years. There were no differences between men and women in the CSF Aβ42/40 ratio or amyloid‐PET, or in the trajectories of tau and neurodegeneration biomarkers. When considering the APOE genotype, women carrying the ε4 allele showed an earlier age at AD diagnosis and higher prevalence of symptomatic AD between ages 40‐45 compared to non‐carriers. The female advantage on mCRT scores was lost in women carrying an ε4 allele.ConclusionSex did not have a main effect on AD risk or biomarker changes. However, APOE ε4 modified the age at symptomatic AD diagnosis and age‐related mCRT scores in women, but not in men. These results emphasize the complexity of the relationship between biological sex and AD, and the need to further explore interactions with APOE ε4.

Neuropsychological correlates of plasma NfL in adults with Down syndrome

AbstractBackgroundThe diagnosis of symptomatic Alzheimer’s disease (AD) in Down syndrome (DS) is challenging, mainly because the variability in cognitive performance associated with the different levels of intellectual disability. Plasma NfL levels are a promising biomarker of axonal damage with good diagnostic and prognostic performance, but its impact on cognitive performance has not been assessed. We aimed to explore this association between NfL levels and both baseline cognitive performance and the longitudinal cognitive decline.MethodProspective longitudinal cohort study. We included adults with DS from the Down Alzheimer Barcelona Neuroimaging Initiative cohort with mild and moderate levels of intellectual disability (ID) who had available plasma and a neuropsychological evaluation (Cambridge Cognitive Examination for Older Adults with Down's syndrome [CAMCOG‐DS] and/or modified Cued Recall Test [mCRT]). Plasma NfL levels were determined by Simoa SR‐XTM. We performed correlation analysis between baseline NfL levels and cognitive scores and linear mixed models to account for longitudinal cognitive measures. Age, sex and cognitive status (asymptomatic, prodromal AD, AD dementia) were considered as co‐variables in the analysis. The analyses were stratified in mild and moderate ID separately.ResultWe selected 378 individuals (mean age: 43.1 [sd 10.9], 46.6% female): 287 had CAMCOG‐DS scores and 224 had mCRT scores. We observed a significant correlation between baseline NfL levels and both CAMCOG‐DS and mCRT (R2=0.18 and R2=0.30, respectively, both p&lt;0.001) (Figure). This correlation remained significant after stratification by ID (R2=0.17 and R2=0.19 for mild ID, R2=0.19 and R2=0.32 for moderate ID, all p&lt;0.001). There was a significant association between longitudinal cognitive scores and baseline NfL levels (β=‐0.0035, p=0.011 for CAMCOG‐DS; β=‐0.015, p&lt;0.001 for mCRT).ConclusionCognitive performance is inversely correlated to plasma NfL levels in adults with DS. This study supports the potential role of plasma NfL levels to identify and track AD‐related cognitive decline in DS.

Brief version of the CAMCOG for illiterate older adults with Alzheimer's dementia.

The Cambridge Cognition Examination (CAMCOG) is one of the most used cognitive assessment batteries for older adults. To evaluate a brief version of the CAMCOG for illiterate older adults (CAMCOG-BILL) with Alzheimer's dementia (AD) and healthy controls (CG). Cross-sectional case-control study with 246 illiterate older adults (AD [n=159] and CG [n=87], composed by healthy seniors without cognitive complaints) who never attended school or took reading or writing lessons. Diagnosis of AD was established based on the NIA-AA and DSM-5 criteria. All participants were assessed with the CAMCOG by a researcher blinded for diagnosis. To assess the consistency of the chosen CAMCOG-BILL sub-items, we performed a binary logistic regression analysis. Both the CAMCOG and the CAMCOG-BILL had satisfactory psychometric properties. The area under the curve (AUC) was 0.932 (p<0.001) for the original version of CAMCOG and 0.936 for the CAMCOG-BILL. Using a cut-off score of ≥60 (CAMCOG) and ≥44 (CAMCOG-BILL), both instruments had the same sensitivity and specificity (89 and 96%, respectively). The CAMCOG-BILL may be a preferred tool because of the reduced test burden for this vulnerable subgroup of illiterate patients with dementia.

Neuropsychiatric Symptoms of Alzheimer's Disease in Down Syndrome and Its Impact on Caregiver Distress.

Neuropsychiatric symptoms (NPS) are non-cognitive manifestations common to dementia and other medical conditions, with important consequences for the patient, caregivers, and society. Studies investigating NPS in individuals with Down syndrome (DS) and dementia are scarce. Characterize NPS and caregiver distress among adults with DS using the Neuropsychiatric Inventory (NPI). We evaluated 92 individuals with DS (≥30 years of age), divided by clinical diagnosis: stable cognition, prodromal dementia, and AD. Diagnosis was determined by a psychiatrist using the Cambridge Examination for Mental Disorders of Older People with Down's Syndrome and Others with Intellectual Disabilities (CAMDEX-DS). NPS and caregiver distress were evaluated by an independent psychiatrist using the NPI, and participants underwent a neuropsychological assessment with Cambridge Cognitive Examination (CAMCOG-DS). Symptom severity differed between-groups for delusion, agitation, apathy, aberrant motor behavior, nighttime behavior disturbance, and total NPI scores, with NPS total score being found to be a predictor of AD in comparison to stable cognition (OR for one-point increase in the NPI = 1.342, p = 0.012). Agitation, apathy, nighttime behavior disturbances, and total NPI were associated with CAMCOG-DS, and 62% of caregivers of individuals with AD reported severe distress related to NPS. Caregiver distress was most impacted by symptoms of apathy followed by nighttime behavior, appetite/eating abnormalities, anxiety, irritability, disinhibition, and depression (R2 = 0.627, F(15,76) = 8.510, p < 0.001). NPS are frequent and severe in individuals with DS and AD, contributing to caregiver distress. NPS in DS must be considered of critical relevance demanding management and treatment. Further studies are warranted to understand the biological underpinnings of such symptoms.

The Impact of a Twelve-Month Comprehensive Program of Cognitive Training for Alzheimer Patients: A Pilot Study

Research has shown that non-pharmacological therapies can be useful in the treatment of Alzheimer’s disease (AD), significantly delaying cognitive decay. However, most AD interventions did not last beyond six months. Hence, little is known about the effect of these programs in the AD patients after six months of treatment. The purpose of this study was to evaluate the efficacy of the twelve-month Comprehensive Program of Cognitive Training (CPCT) for a sample of AD patients and to compare the results with the average annual rate of change. Thirty-nine AD patients participated in the study. The CPCT consists of a set of cognitive stimulations, intervention in activities of daily life (ADL), and motor training for 12 months. All patients were evaluated at baseline and in three-month intervals via the Mini Mental State Examination (MMSE), the Cambridge Cognitive Examination (CAMCOG), the Lawton Instrumental Activities of Daily Living Scale (IADL), and the Global Deterioration Scale (GDS). After CPCT implementation, there were no significant differences in the MMSE, IADL, and GDS evaluations between baseline and twelve months. Concerning the CAMCOG evaluation, there was no significant difference between the baseline and sixth-month assessments. Overall, the participants’ cognitive functioning did not decline when compared to the average annual rate of change. The CPCT extends the benefit of non-pharmacological interventions for AD patients to twelve months. Its implementation might provide the patients’ relatives with some guarantee concerning the delay of the disease. Future research may investigate the efficacy of the CPCT in comparison with a control group and over a more extended period.

Intracranial artery calcifications: Risk factors and association with cardiovascular disease and cognitive function

Background and aimswe know little about clinical outcomes of arterial calcifications. This study investigates the risk factors of intracranial artery calcifications and its association with cardiovascular disease and cognitive function. Methodspatients were recruited from a Dutch memory clinic, between April 2009 and April 2015. The intracranial internal carotid artery (iICA) and basilar artery were analysed on the presence of calcifications. Calcifications in the iICA were also assessed on severity and location in the tunica intima or tunica media. Using logistic regression, risk factors of intracranial artery calcifications were analysed, as well as the association of these calcifications with cardiovascular disease, cognitive function and type of cognitive disorder (including subjective cognitive impairment, mild cognitive impairment and dementia). Cognitive function was assessed with the Cambridge Cognitive Examination. Results1992 patients were included (median age: 78.2 years, ±40% male). The majority of patients had calcifications in the iICA (±95%). Basilar artery calcifications were less prevalent (±8%). Risk factors for cerebral intracranial calcifications were age (p < 0.001), diabetes mellitus (medial iICA, p = 0.004), hypertension (intimal iICA, p < 0.001) and basilar artery, p = 0.019) and smoking (intimal iICA, p = 0.008). iICA calcifications were associated with stroke and intimal calcifications also with myocardial infarction. Intracranial artery calcifications were not associated with cognitive function or type of cognitive disorder. Conclusionthe majority of memory clinic patients had intracranial artery calcifications. Cardiovascular risk factors are differentially related to medial or intimal iICA calcifications. iICA calcifications were associated with myocardial infarction and stroke, but not with cognitive outcomes.

Predictors of Disease Progression in Early-Onset Alzheimer's Dementia: A Retrospective Cohort Study

ObjectivesEarly-onset Alzheimer's disease (EOAD), defined as onset of AD before the age of 65 years, is less common than the late-onset type, and little is known about the factors affecting disease progression. The aim of the study was to investigate factors influencing disease progression in people with EOAD. DesignRetrospective cohort study. Setting and ParticipantsPeople with EOAD who were assessed and attended the specialist memory service at a university teaching hospital in a European setting, between 2000 and 2010. MeasuresSociodemographic details and clinical and cognitive assessments at initial assessment were used as potential predictors of change in clinical status and outcome at final follow-up within the memory service. ResultsOf the 101 people diagnosed with EOAD during this period, 96 patients were followed up (53 women; aged 59 ± 4.9 years; mean follow-up 36.3 ± 29.12 months). Patients were classified as Stable (n = 25) if continued within the memory service or discharged to primary care, and those transferred to other specialist services (n = 66) for further inputs, institutional care (n = 4), or died (n = 1) were classified as Worseners (n = 71). Lower education (P = .008), lower Cambridge Cognition Examination scores (P = .049), and presence of family history of dementia [P = .012, χ2 (1) = 8.84] was associated with worse change in clinical status. Furthermore, cognitive deficits such as lower scores on comprehension, recent memory, and executive functions were found to predict a worse clinical outcome. Conclusions and ImplicationsIdentification of predictors of faster disease progression has significant clinical benefit, allowing clinicians to estimate prognosis and plan patient care accordingly.

Clinical and biomarker changes of Alzheimer's disease in adults with Down syndrome: a cross-sectional study

SummaryBackgroundAlzheimer's disease and its complications are the leading cause of death in adults with Down syndrome. Studies have assessed Alzheimer's disease in individuals with Down syndrome, but the natural history of biomarker changes in Down syndrome has not been established. We characterised the order and timing of changes in biomarkers of Alzheimer's disease in a population of adults with Down syndrome.MethodsWe did a dual-centre cross-sectional study of adults with Down syndrome recruited through a population-based health plan in Barcelona (Spain) and through services for people with intellectual disabilities in Cambridge (UK). Cognitive impairment in participants with Down syndrome was classified with the Cambridge Cognitive Examination for Older Adults with Down Syndrome (CAMCOG-DS). Only participants with mild or moderate disability were included who had at least one of the following Alzheimer's disease measures: apolipoprotein E allele carrier status; plasma concentrations of amyloid β peptides 1–42 and 1–40 and their ratio (Aβ1–42/1–40), total tau protein, and neurofilament light chain (NFL); tau phosphorylated at threonine 181 (p-tau), and NFL in cerebrospinal fluid (CSF); and one or more of PET with 18F-fluorodeoxyglucose, PET with amyloid tracers, and MRI. Cognitively healthy euploid controls aged up to 75 years who had no biomarker abnormalities were recruited from the Sant Pau Initiative on Neurodegeneration. We used a first-order locally estimated scatterplot smoothing curve to determine the order and age at onset of the biomarker changes, and the lowest ages at the divergence with 95% CIs are also reported where appropriate.FindingsBetween Feb 1, 2013, and June 28, 2019 (Barcelona), and between June 1, 2009, and Dec 31, 2014 (Cambridge), we included 388 participants with Down syndrome (257 [66%] asymptomatic, 48 [12%] with prodromal Alzheimer's disease, and 83 [21%] with Alzheimer's disease dementia) and 242 euploid controls. CSF Aβ1–42/1–40 and plasma NFL values changed in individuals with Down syndrome as early as the third decade of life, and amyloid PET uptake changed in the fourth decade. 18F-fluorodeoxyglucose PET and CSF p-tau changes occurred later in the fourth decade of life, followed by hippocampal atrophy and changes in cognition in the fifth decade of life. Prodromal Alzheimer's disease was diagnosed at a median age of 50·2 years (IQR 47·5–54·1), and Alzheimer's disease dementia at 53·7 years (49·5–57·2). Symptomatic Alzheimer's disease prevalence increased with age in individuals with Down syndrome, reaching 90–100% in the seventh decade of life.InterpretationAlzheimer's disease in individuals with Down syndrome has a long preclinical phase in which biomarkers follow a predictable order of changes over more than two decades. The similarities with sporadic and autosomal dominant Alzheimer's disease and the prevalence of Down syndrome make this population a suitable target for Alzheimer's disease preventive treatments.FundingInstituto de Salud Carlos III, Fundació Bancaria La Caixa, Fundació La Marató de TV3, Medical Research Council, and National Institutes of Health.

Cognitive impairment, endothelial biomarkers and mortality in maintenance haemodialysis patients: a prospective cohort study

Haemodialysis (HD) patients have a high prevalence of cardiovascular disease risk factors as well as cognitive impairment. The objective of the present study was to evaluate the interrelationship between cognitive impairment, endothelium-related biomarkers and cardiovascular/non-cardiovascular mortality. A total of 216 outpatients were recruited from three centres in a dialysis network in Brazil between June 2016 and June 2019. Sociodemographic and clinical data were obtained by applying a patient questionnaire, reviewing medical records data and conducting patient interviews. Cognitive function was assessed using the Cambridge Cognitive Examination. Plasma endothelium-related biomarkers [syndecan-1, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion protein-1 (VCAM-1) and angiopoietin-2 (AGPT2)] were measured. Patients were followed for 30 months. Cox proportional hazards regression models were used to assess the associations of the cognitive function scores and each endothelium-related biomarker with cardiovascular/non-cardiovascular mortality. Cognitive function was associated with cardiovascular mortality {each standard deviation [SD] better cognitive score was associated with a 69% lower risk for cardiovascular mortality [hazard ratio (HR) 0.31 [95% confidence interval (CI) 0.17-0.58]} but not with non-cardiovascular mortality. Moreover, cognitive function was also correlated with all endothelial-related biomarkers, except VCAM-1. ICAM-1, AGPT2 and syndecan-1 were also associated with cardiovascular mortality. The association between cognitive function and cardiovascular mortality remained significant with no HR value attenuation [fully adjusted HR 0.32 (95% CI 0.16-0.59)] after individually including each endothelial-related biomarker in the Cox model. In conclusion, cognitive impairment was associated with several endothelium-related biomarkers. Moreover, cognitive impairment was associated with cardiovascular mortality but not with non-cardiovascular mortality, and the association between cognitive impairment and cardiovascular mortality in HD patients was not explained by any of the endothelial-related biomarkers.

Psychometric properties of Cognitive Instruments in Vascular Dementia and Alzheimer's disease: a neuropsychological study

OBJECTIVES:To describe elderly performance in the Bender Gestalt Test (BGT) and to discriminate its score by using types of errors as comparison among healthy controls, Alzheimer’s disease (AD) patients, and vascular dementia (VD) patients.METHODS:We performed a cross-sectional analysis of 285 elderly individuals of both sexes, all over 60 years old and with more than 1 year of schooling. All participants were assessed through a detailed clinical history, laboratorial tests, neuroimaging, and neuropsychological tests including the BGT, the Cambridge Cognitive Examination (CAMCOG), the Mini-Mental State Examination (MMSE), the Geriatric Depression Scale (GDS), and the Pfeffer Functional Activities Questionnaire (PFAQ). The BGT scores were not used to establish diagnosis.RESULTS:Mean BGT scores were 3.2 for healthy controls, 7.21 for AD, and 8.04 for VD with statistically significant differences observed between groups (p<0.0001). Logistic regression analysis was used to identify the main risk factors for the diagnostic groups. BGT’s scores significantly differentiated the healthy elderly from those with AD (p<0.0001) and VD (p<0.0001), with a higher area under the curve, respectively 0.958 and 0.982. BGT’s scores also showed that the AD group presented 12 types of errors. Types of errors evidenced in the execution of this test may be fundamental in clinical practice because it can offer differential diagnoses between senescence and senility.CONCLUSION:A cut-off point of 4 in the BGT indicated cognitive impairment. BGT thus provides satisfactory and useful psychometric data to investigate elderly individuals.

Diagnosis of prodromal and Alzheimer's disease dementia in adults with Down syndrome using neuropsychological tests.

IntroductionWe aimed to define prodromal Alzheimer's disease (AD) and AD dementia using normative neuropsychological data in a large population‐based cohort of adults with Down syndrome (DS).MethodsCross‐sectional study. DS participants were classified into asymptomatic, prodromal AD and AD dementia, based on neurologist's judgment blinded to neuropsychological data (Cambridge Cognitive Examination for Older Adults with Down's syndrome [CAMCOG‐DS] and modified Cued Recall Test [mCRT]). We compared the cutoffs derived from the normative data in young adults with DS to those from receiver‐operating characteristic curve (ROC) analysis.ResultsDiagnostic performance of the CAMCOG‐DS and modified Cued Recall Test (mCRT) in subjects with mild and moderate levels of intellectual disability (ID) was high, both for diagnosing prodromal AD and AD dementia (area under the curve [AUC] 0.73–0.83 and 0.90–1, respectively). The cutoffs derived from the normative data were similar to those derived from the ROC analyses.DiscussionDiagnosing prodromal AD and AD dementia in DS with mild and moderate ID using population norms for neuropsychological tests is possible with high diagnostic accuracy.

Cambridge Cognitive Examination and Hachinski Ischemic Score as predictors of MRI confirmed pathology in dementia: A cross-sectional study.

Dementia is diagnosed through a combination of clinical assessment, cognitive assessment tools and neuroimaging. The aim of this retrospective, naturalistic study was to explore the association between the clinical assessment tools used in a memory clinic and the findings of Magnetic Resonance Imaging (MRI) scans in patients with dementia. Data were collected through routine clinical practice for all patients assessed at a memory assessment clinic in East Sussex, UK. Included patients had an MRI scan and received a formal diagnosis of dementia. Multinomial logistic regression was used to investigate the associations between atrophy on MRI with age, gender, Cambridge Cognitive Examination (CAMCOG) and Hachinski Ischemic Score (HIS). Ordinal logistic regression was used to study the associations between vascular findings on MRI with age, gender, CAMCOG and HIS. Because of the distribution of HIS scores a cut-off of 1 or greater was used in the regression analysis. Male gender was associated with an increased likelihood of moderate atrophy (relative risk ratio (RRR)=1.99, 95% confidence interval (CI)=1.04-3.82), severe atrophy (RRR=3.04, 95%CI=1.38-6.68) and regional atrophy (RRR=2.25, 95%CI=1.26-4.00) on MRI. An increase of one point on the CAMCOG was associated with a decreased risk of regional atrophy (RRR=0.98, 95%CI=0.96-1.00) on MRI. There were no significant associations between age, or HIS, and atrophy on MRI. An increase in age of one year was associated with an increase in severity of vascular pathology reported on MRI (OR=1.08, 95%CI=1.05-1.12). Male gender was associated with reduced severity of vascular pathology reported on MRI (OR=0.53, 95%CI=0.36-0.78). There were no associations between CAMCOG, or HIS, and vascular pathology on MRI. Our data show that CAMCOG was associated with MRI findings of regional atrophy and vascular pathology was greater in older patients. We highlight the importance of using a multi-modal approach to dementia diagnosis.