P3-025: Correlation between ecological evaluation of communication and cognitive test in Alzheimer's disease and normal elderly

AbstractConventional neuropsychological assessments for Alzheimer’s disease are burdensome and inaccurate at detecting mild cognitive impairment and predicting Alzheimer’s disease risk. Altoida’s Digital Neuro Signature (DNS), a longitudinal cognitive test consisting of two active digital biomarker metrics, alleviates these limitations. By comparison to conventional neuropsychological assessments, DNS results in faster evaluations (10 min vs 45–120 min), and generates higher test-retest in intraindividual assessment, as well as higher accuracy at detecting abnormal cognition. This study comparatively evaluates the performance of Altoida’s DNS and conventional neuropsychological assessments in intraindividual assessments of cognition and function by means of two semi-naturalistic observational experiments with 525 participants in laboratory and clinical settings. The results show that DNS is consistently more sensitive than conventional neuropsychological assessments at capturing longitudinal individual-level change, both with respect to intraindividual variability and dispersion (intraindividual variability across multiple tests), across three participant groups: healthy controls, mild cognitive impairment, and Alzheimer’s disease. Dispersion differences between DNS and conventional neuropsychological assessments were more pronounced with more advanced disease stages, and DNS-intraindividual variability was able to predict conversion from mild cognitive impairment to Alzheimer’s disease. These findings are instrumental for patient monitoring and management, remote clinical trial assessment, and timely interventions, and will hopefully contribute to a better understanding of Alzheimer’s disease.

Download Full-text

Enhanced adrenal sensitivity to adrenocorticotrophic hormone (ACTH) is evidence of HPA axis hyperactivity in Alzheimer's disease

Psychological Medicine ◽

10.1017/s0033291700033675 ◽

1996 ◽

Vol 26 (1) ◽

pp. 7-14 ◽

Cited By ~ 40

Author(s):

J. T. O'Brien ◽

D. Ames ◽

I. Schweitzer ◽

M. Mastwyk ◽

P. Colman

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Hpa Axis ◽

Low Dose ◽

Age At Onset ◽

Neuronal Loss ◽

Inverse Correlation ◽

Cognitive Test ◽

Cortisol Response ◽

Adrenocorticotrophic Hormone

SynopsisAdrenal sensitivity was assessed in 16 non-depressed patients with NINCDS/ADRDA Alzheimer's disease (AD) and 18 control subjects by measuring cortisol response to low dose (0·05 μg/kg i.v.) exogenous adrenocorticotrophic hormone (ACTH). Controlling for sex and medication, both peak cortisol level (peak–baseline) and area under cortisol response curve (AUC above baseline) were significantly greater in AD subjects. This shows that HPA axis hyperactivity, as demonstrated by enhanced adrenal sensitivity to ACTH, occurs in AD. Similar findings have been reported to occur in depression. Among AD subjects, AUC cortisol response correlated with current age (r= 0·70,P= 0·001) and age at onset of dementia (r= 0·73,P= 0·001) and an inverse correlation was seen between cortisol AUC and cognitive test (CAMCOG) score (r= −0·51,P= 0·044). Our findings suggest that HPA axis hyperactivity in AD is associated with advancing age and cognitive dysfunction. Such changes may be cause, or consequence, of neuronal loss.

Download Full-text

Callosal Atrophy Correlates with Temporal Lobe Volume and Mental Status in Alzheimer's Disease

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/s0317167100000846 ◽

2000 ◽

Vol 27 (3) ◽

pp. 204-209 ◽

Cited By ~ 23

Author(s):

Sandra E. Black ◽

Scott D. Moffat ◽

David C. Yu ◽

Jayson Parker ◽

Peter Stanchev ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Temporal Lobe ◽

Rating Scale ◽

Anterior Commissure ◽

Cognitive Status ◽

Cognitive Test ◽

Temporal Lobes ◽

Cerebral Commissures ◽

State Examination

Background:Recent studies have reported significant atrophy of the corpus callosum (CC) in Alzheimer's Disease (AD). However, it is currently unknown whether CC atrophy is associated with specific cortical volume changes in AD. Moreover, possible atrophy in extra-callosal commissures has not been examined to date. The purpose of the present study was to quantify atrophy in two cerebral commissures [the CC and the anterior commissure (AC)], to correlate this measure with cognitive status, and to relate commissural size to independent measures of temporal lobe volume in AD patients.Methods:A sample of AD patients and of age- and education-matched normal control subjects (NCs) underwent MRI and a cognitive test battery including the Dementia Rating Scale and Mini Mental State examination. Mid-sagittal regional areas within CC and AC were measured along with superior, middle and inferior temporal lobes volumes.Results:Alzheimer's Disease patients had significantly smaller callosa than did NCs. The callosal regions most affected in AD included the midbody, isthmus and genu. The isthmus and midbody areas of the CC were positively correlated with cognitive performance and with superior temporal lobe volume in AD patients. The mid-sagittal area of the AC and the superior temporal volumes did not differ between AD patients and NCs.Conclusion:The study demonstrated that the regional morphology of the CC correlates with current cognitive status and temporal lobe atrophy in AD. As well, the lack of difference for the AC suggests that commissural atrophy in AD is regionally specific.

Download Full-text

SHORT-TERM PRACTICE EFFECTS AND AMYLOID DEPOSITION: PROVIDING INFORMATION ABOVE AND BEYOND BASELINE COGNITION

Journal of Prevention of Alzheimer's Disease ◽

10.14283/jpad.2017.9 ◽

2017 ◽

pp. 1-6

Author(s):

K. Duff ◽

D.B. Hammers ◽

B.C.A. Dalley ◽

K.R. Suhrie ◽

T.J. Atkinson ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Clinical Trials ◽

Test Scores ◽

Amyloid Deposition ◽

Cognitive Testing ◽

Practice Effects ◽

Cognitive Test ◽

Cognitive Tests ◽

Short Term

Background: Practice effects, which are improvements in cognitive test scores due to repeated exposure to testing materials, may provide information about Alzheimer’s disease pathology, which could be useful for clinical trials enrichment. Objectives: The current study sought to add to the limited literature on short-term practice effects on cognitive tests and their relationship to amyloid deposition on neuroimaging. Participants: Twenty-seven, non-demented older adults (9 cognitively intact, 18 with mild cognitive impairment) received amyloid imaging with 18F-Flutemetamol, and two cognitive testing sessions across one week to determine practice effects. Results: A composite measure of 18F-Flutemetamol uptake correlated significantly with all seven cognitive tests scores on the baseline battery (r’s = -0.61 – 0.59, all p’s<0.05), with higher uptake indicating poorer cognition. Practice effects significantly added to the relationship (above and beyond the baseline associations) with 18F-Flutemetamol uptake on 4 of the 7 cognitive test scores (partial r’s = -0.45 – 0.44, p’s<0.05), with higher uptake indicating poorer practice effects. The odds ratio of being “amyloid positive” was 13.5 times higher in individuals with low practice effects compared to high practice effects. Conclusions: Short-term practice effects over one week may be predictive of progressive dementia and serve as an affordable screening tool to enrich samples for preventative clinical trials in Alzheimer’s disease.

Download Full-text

Ventricular expansion, white matter hyperintensities, and global cognition in Alzheimer’s disease and normal aging

10.1101/2020.11.30.20240879 ◽

2020 ◽

Author(s):

Sabrina Adamo ◽

Joel Ramirez ◽

Melissa F. Holmes ◽

Fuqiang Gao ◽

Ljubica Zotovic ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

White Matter ◽

White Matter Hyperintensities ◽

Small Vessel Disease ◽

Normal Aging ◽

Small Vessel ◽

Cognitive Test ◽

Vessel Disease ◽

Link Type

ABSTRACTBackgroundThe progression of Alzheimer’s Disease (AD) may be tracked by measuring the growth of the ventricular cerebrospinal fluid (vCSF) over time. AD is commonly comorbid with markers of cerebral small vessel disease (SVD), viewed on MRI as white matter hyperintensities (WMH). Larger WMH volumes are correlated with poorer cognitive test scores. Additionally, periventricular WMHs have a proposed relationship to the vCSF.PurposeThis study will examine ventricular expansion and its associations between periventricular/deep WMH and cognition in AD and normal aging.MethodsBaseline and 1-year follow-up data were collected from AD (n=117) and cognitively normal control (NCs; n=49) participants taking part in the Sunnybrook Dementia Study. MRI (1.5T) and scores from both the Mini-Mental State Examination (MMSE) and the Dementia Rating Scale (DRS) were assessed at each time point. Volumetric data was generated using a semi-automated pipeline and each individual’s vCSF and WMHs were transformed to an intermediate space to determine volumetric growth. Regressions were used to determine relationships between vCSF growth measures, SVD burden, and cognition, accounting for demographics and individual interscan intervals.ResultsThe AD group displayed 14.6% annual ventricular growth as opposed to NC who had only 11.8% annual growth. AD showed significant growth in vCSF (p < 0.001), a trend toward greater pWMH growth (p = 0.06) and no difference in dWMH growth volumes compared to NC. vCSF growth was positively associated with pWMH (β = 0.32, p < 0.001) but not dWMH growth in AD while in NC it was associated with both pWMH (β = 0.48, p < 0.001) and dWMH growth (β = 0.35, p = 0.02). In AD, vCSF growth was associated with the both the MMSE (β = -0.30, p < 0.001) and the DRS (β = -0.31, p < 0.001) in separate models.ConclusionsThe findings from this study suggest that in just under 1.5 years, the significantly rapid ventricular expansion observed in AD may be closely related to periventricular small vessel disease. As vCSF growth rates are an important biomarker of AD neurodegeneration that corresponds with cognitive decline, future research should further explore atrophy associated with periventricular vasculopathy.Trial RegistrationClinicalTrials.gov, NCT01800214. Registered on 27 February 2013.

Download Full-text

Neuropsychiatric symptoms and executive function impairments in Alzheimer’s disease and vascular dementia: The role of subcortical circuits

Dementia & Neuropsychologia ◽

10.1590/1980-57642018dn13-030005 ◽

2019 ◽

Vol 13 (3) ◽

pp. 293-298 ◽

Cited By ~ 2

Author(s):

Chan Tiel ◽

Felipe Kenji Sudo ◽

Ana Beatriz Calmon

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Executive Function ◽

Vascular Dementia ◽

Neuropsychiatric Symptoms ◽

Vascular Lesions ◽

Cognitive Test ◽

Pathophysiological Mechanism ◽

Clinical Dementia Rating

ABSTRACT Neuropsychiatric symptoms (NPS) in dementia are prevalent, under-recognized and little studied regarding their pathophysiological aspects. The pathophysiological mechanism, as well as the possible role of vascular lesions in the genesis of these symptoms, are still matters of debate. Objective: to describe and compare the prevalence and severity of NPS in subjects with Alzheimer's disease (AD) and vascular dementia (VaD). Methods: a cross-sectional study involving 82 outpatients, divided into two groups (AD × VaD), was conducted. Patients were submitted to the Cambridge Cognitive Test (CAMCOG), the Clock Drawing Test (CLOX 1 and 2), the Neuropsychiatric Inventory (NPI) and the Clinical Dementia Rating (CDR) scale. Neuroimaging was scored using the de Leon and Fazekas scales. Results: 90.8% of the patients had at least one neuropsychiatric symptom. There were statistical differences on the CLOX test and in the apathy symptoms between AD and VaD groups. Apathy and disinhibition proved more prevalent in patients with higher vascular load. Conclusion: apathy and impaired executive function may reflect vascular damage in subcortical circuits in dementia patients.

Download Full-text

Automatic Prediction of Cognitive and Functional Decline Can Significantly Decrease the Number of Subjects Required for Clinical Trials in Early Alzheimer’s Disease

Journal of Alzheimer s Disease ◽

10.3233/jad-210664 ◽

2021 ◽

pp. 1-8

Author(s):

Neda Shafiee ◽

Mahsa Dadar ◽

Simon Ducharme ◽

D. Louis Collins ◽

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Clinical Trials ◽

Cognitive Decline ◽

Functional Decline ◽

Amyloid Β ◽

Cognitive Test ◽

Disease Heterogeneity ◽

Early Alzheimer’S Disease

Background: While both cognitive and magnetic resonance imaging (MRI) data has been used to predict progression in Alzheimer’s disease, heterogeneity between patients makes it challenging to predict the rate of cognitive and functional decline for individual subjects. Objective: To investigate prognostic power of MRI-based biomarkers of medial temporal lobe atrophy and macroscopic tissue change to predict cognitive decline in individual patients in clinical trials of early Alzheimer’s disease. Methods: Data used in this study included 312 patients with mild cognitive impairment from the ADNI dataset with baseline MRI, cerebrospinal fluid amyloid-β, cognitive test scores, and a minimum of two-year follow-up information available. We built a prognostic model using baseline cognitive scores and MRI-based features to determine which subjects remain stable and which functionally decline over 2 and 3-year follow-up periods. Results: Combining both sets of features yields 77%accuracy (81%sensitivity and 75%specificity) to predict cognitive decline at 2 years (74%accuracy at 3 years with 75%sensitivity and 73%specificity). When used to select trial participants, this tool yields a 3.8-fold decrease in the required sample size for a 2-year study (2.8-fold decrease for a 3-year study) for a hypothesized 25%treatment effect to reduce cognitive decline. Conclusion: When used in clinical trials for cohort enrichment, this tool could accelerate development of new treatments by significantly increasing statistical power to detect differences in cognitive decline between arms. In addition, detection of future decline can help clinicians improve patient management strategies that will slow or delay symptom progression.

Download Full-text

Impact of hearing loss and vestibular decline on cognition in Alzheimer’s disease: a prospective longitudinal study protocol (Gehoor, Evenwicht en Cognitie, GECkO)

BMJ Open ◽

10.1136/bmjopen-2020-039601 ◽

2020 ◽

Vol 10 (9) ◽

pp. e039601

Author(s):

Joyce Bosmans ◽

Cathérine Jorissen ◽

Patrick Cras ◽

Angelique Van Ombergen ◽

Sebastiaan Engelborghs ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Hearing Loss ◽

Longitudinal Study ◽

Study Protocol ◽

Cognitive Test ◽

Secondary Outcome ◽

Prospective Longitudinal Study ◽

Prospective Longitudinal ◽

Mci Due To Ad

IntroductionDementia is a prevalent disease affecting a growing number of the ageing population. Alzheimer’s disease (AD) is the most common cause of dementia. Previous research investigated the link between hearing loss and cognition, and the effect of vestibular dysfunction on cognition. Hearing loss and, to a lesser extent, vestibular decline both result in a decreasing cognitive function. However, their interaction should not be underestimated. The aim of this study is to assess the effect of hearing loss, vestibular decline and their interaction on cognition in people suffering from mild cognitive impairment (MCI) and dementia due to AD (ADD).Methods and analysisWe designed a prospective longitudinal study to assess the effect of hearing loss and vestibular decline on cognition. A total of 100 cognitively impaired elderly (between 55 and 84 years of age), consisting of 60 patients with MCI due to AD and 40 patients with ADD will be included. The control group will consist of individuals with preserved cognition group-matched based on age, hearing level and vestibular function. A comprehensive assessment is performed at baseline, 12-month and 24-month follow-ups. The primary outcome measure is the change in the Repeatable Battery for the Assessment of Neuropsychological Status adjusted for Hearing-impaired individuals total score, a cognitive test battery assessing different cognitive domains. Secondary outcome measures include additional neuropsychological assessments, cortical auditory-evoked potentials, and evaluation of general and disease-specific health-related quality of life. Variables include cognitive, audiological and vestibular evaluation. Variance analyses will assess the effect of hearing loss and vestibular decline on cognition. More precisely, the link between hearing loss and non-spatial cognitive functioning, the effect of vestibular decline on spatial cognition and the impact of both factors on the rate of conversion from MCI due to AD to ADD will be investigated.Ethics and disseminationThe study protocol was approved by the ethical committee of the Antwerp University Hospital on 4 February 2019 with protocol number B300201938949. The findings will be disseminated through peer-reviewed publications and conference presentations.Trial registration numberClinicalTrials.gov Registry (NCT04385225).

Download Full-text

Lack of relation between race and cognitive test performance in Alzheimer's disease

Neurology ◽

10.1212/wnl.50.5.1499 ◽

1998 ◽

Vol 50 (5) ◽

pp. 1499-1501 ◽

Cited By ~ 15

Author(s):

M. C. Carlson ◽

J. Brandt ◽

K. A. Carson ◽

C. H. Kawas

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Test Performance ◽

Cognitive Test ◽

Cognitive Test Performance

Download Full-text

Can the CAMCOG be a good cognitive test for patients with Alzheimer's disease with low levels of education?

International Psychogeriatrics ◽

10.1017/s104161021000116x ◽

2010 ◽

Vol 23 (1) ◽

pp. 96-101 ◽

Cited By ~ 13

Author(s):

Ivan Aprahamian ◽

José Eduardo Martinelli ◽

Juliana Cecato ◽

Rafael Izbicki ◽

Mônica Sanches Yassuda

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Test ◽

Cross Sectional ◽

Educational Levels ◽

Mean Values ◽

Group 3 ◽

Low Levels ◽

Group 2 ◽

Group 1

ABSTRACTBackground: The Cambridge Cognitive Examination (CAMCOG) is a useful test in screening for Alzheimer's disease (AD). However, the interpretation of CAMCOG cut-off scores is problematic and reference values are needed for different educational strata. Given the importance of earlier diagnoses of mild dementia, new cut-off values are required which take into account patients with low levels of education. This study aims to evaluate whether the CAMCOG can be used as an accurate screening test among AD patients and normal controls with different educational levels.Methods: Cross-sectional assessment was undertaken of 113 AD and 208 elderly controls with heterogeneous educational levels (group 1: 1–4 years; group 2: 5–8 years; and group 3: ≥ 9 years) from a geriatric clinic. submitted to a thorough diagnostic evaluation for AD including the Cambridge Examination for Mental Disorders of the Elderly (CAMDEX). Controls had no cognitive or mood complaints. Sensitivity (SE) and specificity (SP) for the CAMCOG in each educational group was assessed with receiver-operator-characteristic (ROC) curves.Results: CAMCOG mean values were lower when education was reduced in both diagnostic groups (controls – group 1: 87; group 2: 91; group 3: 96; AD – group 1: 63; group 2: 62; group 3: 77). Cut-off scores for the three education groups were 79, 80 and 90, respectively. SE and SP varied among the groups (group 1: 88.1% and 83.5%; group 2: 84.6% and 96%; group 3: 70.8% and 90%).Conclusion: The CAMCOG can be used as a cognitive test for patients with low educational level with good accuracy. Patients with higher education showed lower scores than previously reported.

Download Full-text