Development, Spanish Normative Data, and Validation of a Social Cognition Battery in Prodromal Alzheimer’s Disease and Multiple Sclerosis

2020 ◽  
Author(s):  
Alfonso Delgado-Álvarez ◽  
Vanesa Pytel ◽  
Cristina Delgado-Alonso ◽  
Carmen María Olbrich-Guzmán ◽  
Ana Cortés-Martínez ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Social Cognition ◽  
Neuropsychological Tests ◽  
Normative Data ◽  
Reactivity Index ◽  
Cognitive Domains ◽  
Prodromal Ad ◽  
Prodromal Alzheimer’S Disease

Abstract Objectives The assessment of social cognition changes may be challenging, especially in the earliest stages of some neurodegenerative diseases. Our objective was to validate a social cognition battery from a multidomain perspective. In this regard, we aimed to adapt several tests, collect normative data, and validate them in prodromal Alzheimer’s disease (AD) and multiple sclerosis (MS). Methods A total of 92 healthy controls, 25 prodromal AD, and 39 MS patients were enrolled. Age-, gender-, and education-matched control groups were created for comparisons. Social cognition battery was composed of an emotion-labeling task developed from FACES database, the Story-based Empathy test (SET), the Faux Pas test, and the Interpersonal Reactivity Index. Patients were also evaluated with a comprehensive cognitive battery to evaluate the other cognitive domains. Automatic linear modeling was used to predict each social cognition test’s performance using the neuropsychological tests examining other cognitive domains. Results The reliability of the battery was moderate-high. Significant intergroup differences were found with medium-large effect sizes. Moderate correlations were found between social cognition battery and neuropsychological tests. The emotion labeling task and SET showed moderate correlations with age and education, and age, respectively. Regression-based norms were created considering the relevant demographic variables. Linear regression models including other neuropsychological tests explained between 7.7% and 68.8% of the variance of the social cognition tests performance. Conclusions Our study provides a battery for the assessment of social cognition in prodromal AD and MS with Spanish normative data to improve the evaluation in clinical and research settings.

scholarly journals Determining Filipino Normative Data for a Battery of Neuropsychological Tests: The Filipino Norming Project (FNP)

2019 ◽  
Vol 9 (2) ◽  
pp. 260-270
Author(s):  
Jacqueline Cotoong Dominguez ◽  
Thien Kieu Thi Phung ◽  
Ma. Fe Payno de Guzman ◽  
Krizelle Cleo Fowler ◽  
Macario Reandelar Jr ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neuropsychological Tests ◽  
Normative Data ◽  
Neuropsychological Test ◽  
Test Battery ◽  
Cognitive Domains ◽  
Neuropsychological Test Battery ◽  
The Mean ◽  
Effect Of Age

Background: Filipino normative data for neuropsychological tests are lacking. Objectives: This study aimed to determine the Filipino normative data for the Filipino Norming Project (FNP) Neuropsychological Battery, combining the Alzheimer’s Disease Assessment Scale – Cognitive (ADAS-Cog) and the Neuropsychological Test Battery from the Uniform Dataset of Alzheimer’s Disease Center (UDS-ADC). Methods: We recruited participants 60 years and older with normal cognition (MMSE score of 25 and above and did not fulfill criteria for dementia according to DSM-IV criteria). Psychologists administered the tests to the study participants. We conducted multivariate analyses to study the effect of age, gender, and education on test performance. Results: A total of 191 participants underwent the FNP Neuropsychological Test Battery. The mean age was 68.8 years (SD 5.4). The majority were female (84.1%). The mean score of ADAS-Cog was 9.98 (SD 4.74). The effect of education was prominent throughout the cognitive domains tested while the effect of age was limited to a few cognitive domains. The mean ADAS-Cog scores were 11.80 ± 4.40 for primary education, 9.93 ± 5.08 for secondary, and 8.15 ± 3.95 for tertiary. On average, women scored 2.75 points lower than men and performed better on the verbal components. Men performed better on the constructional praxis component. The same effect of education and gender was observed for the UDS-ADC. Conclusion: For the first time, normative data are available for the ADAS-Cog and UDS-ADC for a Filipino older population. This study stresses the importance of establishing population-specific normative data, taking into account the specific sociocultural and linguistic context of that population.

scholarly journals Psychometric Properties of the Clinical Dementia Rating – Sum of Boxes and Other Cognitive and Functional Outcomes in a Prodromal Alzheimer’s Disease Population

2020 ◽  
pp. 1-10
Author(s):  
F. McDougall ◽  
C. Edgar ◽  
M. Mertes ◽  
P. Delmar ◽  
P. Fontoura ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trial ◽  
Psychometric Properties ◽  
Disease Assessment ◽  
Clinical Dementia Rating ◽  
Prodromal Ad ◽  
Ceiling Effects ◽  
Prodromal Alzheimer’S Disease ◽  
Selective Reminding Test

BACKGROUND: The Clinical Dementia Rating–Sum of Boxes (CDR-SB) has been proposed as a primary outcome for use in prodromal AD trials. However, the psychometric properties of this, and of other commonly used measures, have not been well-established in this patient population. OBJECTIVE: To describe the psychometric properties of commonly used efficacy measures in a clinical trial of prodromal AD. SETTING: Data were gathered as part of a two-year clinical trial. PARTICIPANTS: Patients had biomarker confirmed prodromal AD. MEASUREMENTS: Clinical Dementia Rating (CDR), Functional Activities Questionnaire (FAQ), Alzheimer’s Disease Assessment Scale – Cognition Subscale 11 and 13 (ADAS-Cog), Mini Mental State Exam (MMSE), and Free and Cued Selective Reminding Test (FCSRT-IR [words]). Assessments were conducted at least every 24 weeks. RESULTS: For the CDR-SB, test-retest reliability was good (intra-class correlation coefficient [ICC]=0.83); internal consistency was 0.65 at baseline but above 0.8 at later assessments. Relationships between the CDR-SB and other measures were as expected (higher correlations with more closely related constructs), and the CDR-SB differentiated between patients with different severities of dementia (-2.9 points difference between CDR-Global Score 0.5 and 1, P<.0001). Floor and ceiling effects on the CDR-SB total score were minimal; however, at baseline there were ceiling effects in the personal care domain. Further detail is provided on the psychometric properties of ADAS-Cog, MMSE, FCSRT-IR and FAQ in this population. CONCLUSION: The psychometric properties of the CDR-SB are adequate in prodromal AD and continued use is warranted in clinical trials. However, there remains scope for improvement in the assessment of functional constructs and development of novel measures should continue.

scholarly journals CSF in Epileptic Prodromal Alzheimer's Disease: No Diagnostic Contribution but a Pathophysiological One

2021 ◽  
Vol 12 ◽  
Author(s):  
Benjamin Cretin ◽  
Olivier Bousiges ◽  
Geoffroy Hautecloque ◽  
Nathalie Philippi ◽  
Frederic Blanc ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
White Matter ◽  
White Matter Hyperintensities ◽  
Surrogate Marker ◽  
Brain Magnetic Resonance Imaging ◽  
Csf Biomarkers ◽  
Epileptiform Discharges ◽  
Prodromal Ad ◽  
Prodromal Alzheimer’S Disease

Objective: To study whether cerebrospinal fluid (CSF) analysis may serve as a diagnostic test for the screening of epilepsy in sporadic prodromal Alzheimer's disease (AD).Methods: A total of 29 patients with epileptic prodromal sporadic AD patients (epADs) were included and were retrospectively compared with 38 non-epileptic prodromal AD patients (nepADs) for demographics, clinical features, Mini-Mental Status Examination (MMSE) results, CSF biomarkers, and electro-radiological features.Results: Our study did not show any significant differences in CSF biomarkers regarding neurodegeneration, albumin levels, and inflammation between epADs and nepADs. The epADs were significantly older at diagnosis (p = 0.001), more hypertensive (p = 0.01), and displayed larger white matter hyperintensities on brain magnetic resonance imaging (MRI; p = 0.05). There was a significant correlation between the CSF Aβ-42 and Aβ-40 levels with interictal epileptiform discharges and delta slowing on EEGs recordings, respectively (p = 0.03).Conclusions: Our study suggests that CSF may not serve as a surrogate marker of epilepsy in prodromal AD and cannot circumvent the operator-dependent and time-consuming interpretation of EEG recordings. In humans, AD-related epileptogenesis appears to involve the Aβ peptides but likely also additional non-amyloid factors such as small-vessel disease (i.e., white matter hyperintensities).

scholarly journals Economic evaluation of supplementing the diet with Souvenaid in patients with prodromal Alzheimer’s disease

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Javier Mar ◽  
Ania Gorostiza ◽  
Oliver Ibarrondo ◽  
Igor Larrañaga ◽  
Arantzazu Arrospide ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Societal Perspective ◽  
Cost Utility ◽  
Simulated Patients ◽  
Parameter Uncertainties ◽  
Modest Improvement ◽  
Prodromal Ad ◽  
Prodromal Alzheimer’S Disease ◽  
The Cost

Abstract Background The LipiDiDiet trial showed that Souvenaid, a medical food, might delay progression to dementia in prodromal Alzheimer’s disease (AD). The objective of this study was to assess the cost-utility of Souvenaid compared to placebo in patients with prodromal AD under the conditions applied in that trial. Methods A discrete event simulation model was developed based on the LipiDiDiet trial and a literature review to assess the cost-utility of Souvenaid from a societal perspective considering direct and indirect costs. For both intervention and control groups, patient trajectories in terms of functional decline on the Clinical Dementia Rating Sum of Boxes (CDR-SB) scale in LipiDiDiet were reproduced statistically with mixed models by assigning time until events to simulated patients. From the societal perspective, four scenarios were analysed by combining different options for treatment duration and diagnostic test cost. Univariate sensitivity analysis assessed parameter uncertainties. Results Validation results at year 2 of disease progression fit with CDR-SB progression in LipiDiDiet. The incremental cost-utility ratio (ICUR) in the baseline case was €22,743/quality-adjusted life year (QALY). All scenarios rendered an ICUR lower than €25,000/QALY (the societal threshold). Moreover, the treatment option was cost-saving and increased health benefits when diagnostic costs were not considered and treatment was only administered during the prodromal stage. Conclusions Treating prodromal AD with Souvenaid is a cost-effective intervention in all scenarios analysed. The LipiDiDiet trial showed a modest improvement in disease course but as the social costs of AD are very high, the intervention was efficient. Assessing small benefits at specific stages of AD is relevant because it is reasonable to expect that no effective, safe and affordable disease-modifying therapies will become available in the short to medium term.

MRI-Based Alzheimer’s Disease-Resemblance Atrophy Index in the Detection of Preclinical and Prodromal Alzheimer’s Disease

2020 ◽  
Author(s):  
Wanting Liu ◽  
Lisa Wing Chi Au ◽  
Jill Abrigo ◽  
Yishan Luo ◽  
Adrian Wong ◽  
...  
Keyword(s):  
Machine Learning ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Hippocampal Volume ◽  
Prodromal Stage ◽  
Preclinical Ad ◽  
Volume Sensitivity ◽  
Prodromal Ad ◽  
Prodromal Alzheimer’S Disease ◽  
Higher Sensitivity

Abstract Background: We aimed to validate the performance of an MRI-based machine learning derived Alzheimer’s Disease-resemblance atrophy index (AD-RAI) in detecting preclinical and prodromal AD. Methods: A total of 62 subjects (mild cognitive impairment [MCI]=25, cognitively unimpaired [CU]=37) underwent MRI, 11C- PIB, and 18F-T807 PET. We investigated the performance of AD-RAI at the pre-specified cutoff of ≥ 0.5 in detecting preclinical and prodromal AD and compared its performance with that of visual and volumetric hippocampal measures. Results: AD-RAI achieved the best metrics among all subjects (sensitivity 0.73, specificity 0.91, accuracy 87.10%) and among MCI subgroup (sensitivity 0.91, specificity 0.79, accuracy 84.00%) in detecting A+T+ subjects over other measures. Among CU subgroup, hippocampal volume (sensitivity 0.75, specificity 0.88, accuracy 86.49%) achieved a higher sensitivity than AD-RAI (sensitivity 0.25, specificity 0.97, accuracy 89.19%) in detecting preclinical AD.Conclusions: AD-RAI aids the detection of early AD, in particular at the prodromal stage.

scholarly journals Brainstem Volumetric Integrity in Preclinical and Prodromal Alzheimer’s Disease

2020 ◽  
Vol 77 (4) ◽  
pp. 1579-1594 ◽  
Author(s):  
Shubir Dutt ◽  
Yanrong Li ◽  
Mara Mather ◽  
Daniel A. Nation ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Locus Coeruleus ◽  
Region Of Interest ◽  
Intracranial Volume ◽  
Cognitively Normal ◽  
Normal Individuals ◽  
Prodromal Ad ◽  
Brainstem Nuclei ◽  
Prodromal Alzheimer’S Disease

Background: Neuropathological studies have suggested the tau pathology observed in Alzheimer’s disease (AD) originates in brainstem nuclei, but no studies to date have quantified brainstem volumes in clinical populations with biomarker-confirmed mild cognitive impairment (MCI) or dementia due to AD or determined the value of brainstem volumetrics in predicting dementia. Objective: The present study examined whether MRI-based brainstem volumes differ among cognitively normal older adults and those with MCI or dementia due to AD and whether preclinical brainstem volumes predict future progression to dementia. Methods: Alzheimer’s Disease Neuroimaging Initiative participants (N = 1,629) underwent baseline MRI scanning with variable clinical follow-up (6–120 months). Region of interest and voxel-based morphometric methods assessed brainstem volume differences among cognitively normal (n = 814), MCI (n = 542), and AD (n = 273) participants, as well as subsets of cerebrospinal fluid biomarker-confirmed MCI (n = 203) and AD (n = 160) participants. Results: MCI and AD cases showed smaller midbrain volumes relative to cognitively normal participants when normalizing to whole brainstem volume, and showed smaller midbrain, locus coeruleus, pons, and whole brainstem volumes when normalizing to total intracranial volume. Cognitively normal individuals who later progressed to AD dementia diagnosis exhibited smaller baseline midbrain volumes than individuals who did not develop dementia, and voxel-wise analyses revealed specific volumetric reduction of the locus coeruleus. Conclusion: Findings are consistent with neuropathological observations of early AD-related pathology in brainstem nuclei and further suggest the clinical relevance of brainstem substructural volumes in preclinical and prodromal AD.

scholarly journals APOE ɛ4 Allele and Financial Capacity Performance in Mild Alzheimer’s Disease: A Pilot Study

2021 ◽  
Vol 5 (1) ◽  
pp. 93-97
Author(s):  
Vaitsa Giannouli ◽  
Magda Tsolaki
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neuropsychological Tests ◽  
Property Law ◽  
Legal Capacity ◽  
Specific Test ◽  
Cognitive Domains ◽  
Financial Capacity ◽  
E4 Allele ◽  
Capacity Performance

This study aims to explore a little investigated topic, i.e., whether the presence of the APOE eɛ4 allele in patients with a diagnosis of mild Alzheimer’s disease (AD) can influence financial capacity. Twenty-eight elders with mild AD carrying the APOE ɛ4 allele and 28 matched non-carrier patients were examined with an extensive battery of neuropsychological tests, and a specific test measuring financial capacity: Legal Capacity for Property Law Transactions Assessment Scale (LCPLTAS). The presence of the APOE ɛ4 allele does not differentiate the group of mild AD patients regarding a number of cognitive domains necessary for financial capacity scores as measured by LCPLTAS.

scholarly journals Plasma sex hormone-binding globulin predicts neurodegeneration and clinical progression in prodromal Alzheimer's disease

2019 ◽  
Author(s):  
Wei Xu ◽  
Bing-Jie Su ◽  
Xue-Ning Shen ◽  
Yan-Lin Bi ◽  
Chen-Chen Tan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Brain Metabolism ◽  
Sex Hormone ◽  
Sex Hormone Binding Globulin ◽  
Hormone Binding ◽  
Clinical Progression ◽  
Cross Sectional ◽  
Prodromal Ad ◽  
Prodromal Alzheimer’S Disease

Abstract Background: Sex hormone-binding globulin (SHBG) in plasma has been found to be significantly elevated in subjects with AD. We aimed to investigate whether plasma SHBG was associated with AD biomarkers and could predict neurodegeneration and clinical progression in prodromal AD.Methods: The study tested the cross-sectional relationship between plasma SHBG and CSF AD biomarkers in 707 non-demented adults. Next, the longitudinal influences of plasma SHBG at baseline on dynamic changes of CSF Aβ42, hippocampus volume, brain metabolism, and cognition were explored in 448 non-demented adults from the Alzheimer’s disease Neuroimaging Initiative (ADNI). Finally, the influence of plasma SHBG on the risk of incident AD was explored. Results: This study included 707 participants (mean [SD] age, 62.5 [10.5] years, 416 [58.8%] female) from CABLE and 448 from ADNI-1 (mean [SD] age, 74.8 [7.2] years, 166 [37.5%] female). A positive correlation was found for SHBG levels in plasma and CSF (p = 2.12 × 10 -10, r = 0.44). Cross-sectional analyses indicated that individuals with higher plasma SHBG had lower levels of CSF Aβ42 (p < 0.005), after adjusting for age, gender, education, APOE4 allele, and cognitive scores. The longitudinal data showed that higher levels of plasma SHBG contribute to accelerated CSF Aβ42 decrease (p < 0.0005), brain metabolism decline (p < 0.05), hippocampus atrophy (p < 0.01), cognitive decline (p < 0.01), and higher risk of AD dementia (p < 0.05).Conclusions: Plasma SHBG is associated with CSF Aβ42 levels and could predict neurodegeneration and clinical progression in prodromal AD. This finding indicates plasma SHBG is a potentially useful, early biomarker for AD.

Alzheimer’s Disease

2017 ◽  
Author(s):  
Michael S. Rafii
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Memory Impairment ◽  
Memory Function ◽  
Hippocampal Atrophy ◽  
Gradual Decline ◽  
Common Cause ◽  
Cognitive Domains ◽  
Prodromal Ad ◽  
Asymptomatic Phase

Alzheimer’s disease (AD) is the most common cause of dementia worldwide, and is characterized by a protracted asymptomatic phase estimated to begin approximately 15 to 20 years. Clinically, AD initially manifests itself by progressive memory impairment, specifically, a loss of episodic memory function characterized by impaired free recall that does not improve with cueing. This is followed by a gradual decline in other cognitive domains leading to functional dependency, which essentially defines the dementia phase of the illness and has been the cornerstone of diagnostic criteria. About 50% of all MCI patients progress to Alzheimer’s dementia, and therefore MCI is thought to represent prodromal AD when they harbor the pathological changes associated with AD, including hippocampal atrophy, elevated CSF amyloid and Tau, as well as the presence of amyloid on PET scan.

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