Working Memory Functioning in Alzheimer's Disease and Vascular Dementia (MEMTRAV-COG)

Efficacy of Working Memory Maintenance Mechanisms in Alzheimer's Disease and Vascular Dementia

The aim of the present study is to investigate potential cognitive mechanisms contributing to working memory impairment in Alzheimer's disease and vascular dementia. The investigators consider a new hypothesis suggesting that difficulties in mobilizing maintenance strategies of information could explain this working memory deficit. More specifically, the investigators assume that patient groups will have difficulties in employing both refreshing and elaborative strategies during a working memory task (i.e., complex span task), as compared to a control group.

Study Overview

• Status: Not yet recruiting
• Conditions: Alzheimer Disease; Vascular Dementia; Mixed Dementias
• Intervention / Treatment: Behavioral: Complex span task; Diagnostic test: Clinical neuropsychological assessment; Diagnostic test: Clinical neurospychological assessement

Detailed Description

Working memory is considered as a central hub in human cognition. Good working memory capacities are fundamental for daily life. However, previous research has indicated that patients with Alzheimer's disease or vascular dementia have significant working memory impairment. Currently, there is no consensus on the cognitive mechanisms responsible for this deficit. Prior findings have highlighted that patients with Alzheimer's disease and/or vascular dementia demonstrate specific difficulties in dual-task situations. In this context, the investigators hypothesize that the continuous alternation between maintenance and processing phases involved in working memory could be impaired for these patients. Thus, the aim of the present study is to investigate if patients with Alzheimer's disease and/or vascular dementia can use maintenance strategies of information in working memory, as typically observed in individuals without cognitive impairments.

To this end, the investigators propose a short working memory task in which they manipulate the opportunities to use refreshing strategies and elaborative strategies. The investigators expect that patients with Alzheimer's disease, vascular dementia, or mixed dementia will benefit less than healthy older adults from the increased opportunities to employ refreshing and elaboration. These difficulties could account for the impaired working memory performance associated with these diseases.

In a second step, the investigators formulate distinctive hypotheses between patient sub-groups:

• On the one hand, Alzheimer's disease is characterized by salient impairment of episodic long-term memory. Consequently, the investigators hypothesize that the working memory decline could be related to this deficit in long-term memory. Specifically, patients with Alzheimer's disease would have greater difficulty in implementing elaboration strategies. Thus, these patients' recall performance should benefit less from semantic links between the to-be-remembered items compared to patients with vascular dementia.
• On the other hand, vascular dementia is characterized by a significant impairment of executive functioning. Thus, the investigators hypothesize that the working memory decline could be related to difficulties in implementing refreshing strategies (i.e., voluntary control of attention). Thus, the recall performance of these patients should benefit less from increased free time during the task, compared to patients with Alzheimer's disease.
• Finally, very few studies have been carried out on patients with mixed dementia (from both Alzheimer's disease and vascular dementia). The investigators assume that the recall performance of these patients will benefit less from elaborative opportunities compared to patients with dementia vascular, and less from refreshing opportunities compared to patients with Alzheimer's disease.

• Study Type: Observational
• Enrollment (Estimated): 120

Contacts and Locations

• Study Contact: Name: Amelie Bichon; Phone Number: 0476728161; Email: abichon@chu-grenoble.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

The population of this study will consist of patients performing a neuropsychological assessment at Grenoble-Alpes University Hospital. These patients consult because of cognitive disorders. The patients are dividied into these three subgroups according to their medical diagnosis of Alzheimer's disease, vascular dementia, or mixed dementia (diagnostic criteria : Dubois et al. (2021) for Alzheimer's disease; VASCOG diagnostic criteria : Sachdev et al., 2015 for vascular dementia; and diagnostic criteria : DSM-V (APA, 2013) for mixed dementia due to Alzheimer and vascular etiology). The population of this study will also include healthy participants (carers/visitors of patients at the Gerontology centre or volunteers at Gerontology centre).

Description

Inclusion Criteria:

• For patient and control groups: Adults ≥ 65 years of age
• For patient and control groups: Native French speaker
• For patient and control groups: Vision for easy reading
• For patient and control groups: Hearing for easy instruction understanding
• For patient and control groups: Back span ≥ 3 during the "Digit Span Backward" subtest (WAIS-IV)
• For patient and control groups: Formulation of the non-opposition to participate in this study
• For patient group only: Consultation in Grenoble University Hospital (Centre de Gérontologie Sud - Gerontology center) for clinical neuropsychological assessment due to suspected cognitive impairment
• For patient group only: Diagnosis of Alzheimer's disease, vascular dementia, or mixed dementia (i.e., Alzheimer's disease and vascular dementia)
• For patient group only: Have undergone a neuropsychological assessment at the day clinic, less than 6 months old.
• For patient group only: Have obtained a medical opinion stating that there is no contraindication to participate in this study and no concurrent pathology that could impair the patient's cognitive abilities.
• For patient group only: Absence of praxis and language disorders thath might prevent the carrying out of the experimental task.
• For patient group only: MMSE score between 18 and 25 included
• For control group only: External visitor/carer of a patient/resident of Grenoble University Hospital or volunteers at Grenoble University Hospital.
• For control group only: MMSE score ≥ 26

Exclusion Criteria:

• For patient and control groups: People under guardianship or deprived of their freedom
• For patient and control groups: Diagnosis of severe psychiatric disorders
• For patient and control groups: Suspicion of pathologies related to alcohol dependence
• For patient and control groups: No French social security coverage
• For patient and control groups: Refusal to voluntarily participate in this study
• For patient and control groups: People covered by articles L1121-5 to L1121-8 of the French Public Health Code
• For patient group only: Suspicion of another neurodegenerative disease, such as fronto-temporal dementia, Parkinson's disease, Lewy body disease.
• For patient group only: Clinical neuropsychological assessment did not reveal any cognitive impairment.

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Alzheimer disease; Alzheimer's disease is define on the basis of the medical diagnostic. As part of routine care, they undergo a standardized clinical neuropsychological assessment that evaluates several cognitive functions. For the study and during the day of medical consultations, each patient will perform a working memory task, lasting approximately 30 minutes. If the patient is accompanied by a family member, the investigators ask the latter to complete a questionnaire on patient's daily executive functioning (French version of the Behavior rating inventory of executive function [BRIEF-A]).	Behavioral: Complex span task; The intervention consists in a computerized working memory task. This task follows the design of a complex span task, involving alternation between memorization and processing steps. For each trial, participants have to memorize French words. These words are sequentially displayed on the screen. Between each word, participants perform a processing task consisting in a spatial location task: They have to determine if a shape is at the top or at the bottom of the screen. After each processing episode, participants have a free time (i.e., available time to maintain information in WM). At the end of each trial, participants perform an orally immediate recall. This experimental task involves several conditions in order to manipulate the opportunities for the spontaneous use of refreshing and elaborative strategies.; Other Names: Working memory task; Diagnostic test: Clinical neuropsychological assessment; As part of routine care, participants in the patient group undergo a standardized clinical neuropsychological assessment that evaluates several cognitive functions. The investigators hypothesize correlations between working memory performance during the experimental task and the results of neuropsychological tests. Thus, the investigators consider the results to several French versions of neuropsychological tests: MMSE (Mini-Mental State Examination); "Digit Span Backward" subtest (WAIS-IV); Stroop Test; Trail Making Test (TMT); Rappel Libre - Rappel Indicé à 16 items or GERIA-12; Category fluences; Instrumental Activities of Daily Living and ADL .
Vascular dementia; Vascular dementia is define on the basis of the medical diagnostic. As part of routine care, they undergo a standardized clinical neuropsychological assessment that evaluates several cognitive functions. For the study and during the day of medical consultations, each patient will perform a working memory task, lasting approximately 30 minutes. If the patient is accompanied by a family member, the investigators ask the latter to complete a questionnaire on patient's daily executive functioning (French version of the Behavior rating inventory of executive function [BRIEF-A]).	Behavioral: Complex span task; The intervention consists in a computerized working memory task. This task follows the design of a complex span task, involving alternation between memorization and processing steps. For each trial, participants have to memorize French words. These words are sequentially displayed on the screen. Between each word, participants perform a processing task consisting in a spatial location task: They have to determine if a shape is at the top or at the bottom of the screen. After each processing episode, participants have a free time (i.e., available time to maintain information in WM). At the end of each trial, participants perform an orally immediate recall. This experimental task involves several conditions in order to manipulate the opportunities for the spontaneous use of refreshing and elaborative strategies.; Other Names: Working memory task; Diagnostic test: Clinical neuropsychological assessment; As part of routine care, participants in the patient group undergo a standardized clinical neuropsychological assessment that evaluates several cognitive functions. The investigators hypothesize correlations between working memory performance during the experimental task and the results of neuropsychological tests. Thus, the investigators consider the results to several French versions of neuropsychological tests: MMSE (Mini-Mental State Examination); "Digit Span Backward" subtest (WAIS-IV); Stroop Test; Trail Making Test (TMT); Rappel Libre - Rappel Indicé à 16 items or GERIA-12; Category fluences; Instrumental Activities of Daily Living and ADL .
Mixed dementia; Mixed dementia (i.e., Alzheimer's disease and vascular dementia) is define on the basis of the medical diagnostic. As part of routine care, they undergo a standardized clinical neuropsychological assessment that evaluates several cognitive functions . For the study and during the day of medical consultations, each patient will perform a working memory task, lasting approximately 30 minutes. If the patient is accompanied by a family member, the investigators ask the latter to complete a questionnaire on patient's daily executive functioning (French version of the Behavior rating inventory of executive function [BRIEF-A]).	Behavioral: Complex span task; The intervention consists in a computerized working memory task. This task follows the design of a complex span task, involving alternation between memorization and processing steps. For each trial, participants have to memorize French words. These words are sequentially displayed on the screen. Between each word, participants perform a processing task consisting in a spatial location task: They have to determine if a shape is at the top or at the bottom of the screen. After each processing episode, participants have a free time (i.e., available time to maintain information in WM). At the end of each trial, participants perform an orally immediate recall. This experimental task involves several conditions in order to manipulate the opportunities for the spontaneous use of refreshing and elaborative strategies.; Other Names: Working memory task; Diagnostic test: Clinical neuropsychological assessment; As part of routine care, participants in the patient group undergo a standardized clinical neuropsychological assessment that evaluates several cognitive functions. The investigators hypothesize correlations between working memory performance during the experimental task and the results of neuropsychological tests. Thus, the investigators consider the results to several French versions of neuropsychological tests: MMSE (Mini-Mental State Examination); "Digit Span Backward" subtest (WAIS-IV); Stroop Test; Trail Making Test (TMT); Rappel Libre - Rappel Indicé à 16 items or GERIA-12; Category fluences; Instrumental Activities of Daily Living and ADL .
Control group; Control group includes healthy older adults (without cognitive impairment). As patient group, control group will perform the working memory task. However, control group does not undergo the clinical neuropsychological assessment.	Behavioral: Complex span task; The intervention consists in a computerized working memory task. This task follows the design of a complex span task, involving alternation between memorization and processing steps. For each trial, participants have to memorize French words. These words are sequentially displayed on the screen. Between each word, participants perform a processing task consisting in a spatial location task: They have to determine if a shape is at the top or at the bottom of the screen. After each processing episode, participants have a free time (i.e., available time to maintain information in WM). At the end of each trial, participants perform an orally immediate recall. This experimental task involves several conditions in order to manipulate the opportunities for the spontaneous use of refreshing and elaborative strategies.; Other Names: Working memory task; Diagnostic test: Clinical neurospychological assessement; Participants in the control group undergo 2 tests clinical that evaluate cognitive functioning. The investigators consider the results to French versions of these neuropsychological tests: MMSE (Mini-Mental State Examination; ); "Digit Span Backward" subtest (WAIS-IV)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Memory performance in the Working memory task	Percentage of correct immediate recall, computed with strict serial recall criterion (item identity + correct position) and computed with item recall criterion (item identity only).	15 minutes
Processing performance in the Working memory task	Percentage of correct response in the spatial part of working memory task	15 minutes
Reaction time	Reaction time for each distractor (in ms) in the spatial part of working memory task	30 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mini-Mental State Examination (MMSE)	MMSE is a test evaluate global cognitive functioning Score from 0 to 30 A higher score mean a better cognitive efficiency	15 minutes
Digit span forward WAIS IV (digit number)	The participant's span is noted, corresponding to the longest number of sequential digits that can be repeated forward.	5 minutes
Digit span forward WAIS IV (standard note)	This scale permitted to obtain a standard note from 0 to 19 A higher score means a better performance	5 minutes
Digit span backward WAIS IV (digit number)	The participant's span is noted, corresponding to the longest number of sequential digits that can be repeated backward.	5 minutes
Digit span backward WAIS IV (standard note)	This scale permitted to obtain a standard note from 0 to 19 A higher score means a better performance	5 minutes
Stroop Test - denomination part	the denomination part of stroop test measures processing speed time is taken, in seconds	30 secondes
Stroop Test - minor interference part (Time)	this part of stroop test measures low inhibition process time is taken, in seconds	30 secondes
Stroop Test - minor interference part (errors)	this part of stroop test measures low inhibition process number of errors is noted, from 0 to 24	30 secondes
Stroop Test - major interference part (time)	this part of stroop test measures strong inhibition process time is taken, in seconds	90 secondes
Stroop Test - major interference part (errors)	this part of stroop test measures strong inhibition process number of errors is noted, from 0 to 24	90 secondes
Trail Making Test - Part A (time)	This test evaluate motor speed processing Time in seconds	2 minutes
Trail Making Test - Part A (errors)	This test evaluates motor speed processing Number of errors is noted	2 minutes
Trail Making Test - Part B (time)	This test evaluates mental flexibility Time in seconds	5 minutes
Trail Making Test - Part B (errors)	This test evaluates mental flexibility Number of errors is noted	5 minutes
Category fluences	Number of correct words is noted	5 minutes
Memory evaluation (16-item Free and Cued Recall, or GERIA-12)	These tests evaluate verbal episodic memory Scores are noted for each trail, from 0 to 16 (RL-RI/16) or 0 to 12 (Geria-12) A higher score means a better performance	40 minutes
Naming task	This test evaluate the capacity to correctly name a picture Score is noted, from 0 to 40 A higher score means a better performance	40 minutes
Behavior rating inventory of executive function	Questionnaire (french version) on patient's daily executive functioning, completed by a relative of the patient, if present Global score from 75 to 225, composing by several composite scores. A higher score means a more severe executive dysfonctionning in daily life	10 minutes
Instrumental Activities of Daily Living	Questionnaire completed by a professional (nurse or doctor) with the patient and an accompagniant if present Score from 0 to 8 A higher score mean a better autonomy in daily life	5 minutes
Activities of Daily Living	Questionnaire completed by a professional (nurse or doctor) with the patient and an accompagniant if present Score from 0 to 6 A higher score mean a better autonomy in daily life	5 minutes

Collaborators and Investigators

• Sponsor: University Hospital, Grenoble
• Collaborators: University Grenoble Alps; Centre National de la Recherche Scientifique, France; Laboratoire de Psychologie et NeuroCognition; Université Savoie Mont Blanc
• Investigators: Study Chair: Benoit Lemaire, Laboratoire de Psychologie et NeuroCognition; Study Chair: Sophie Portrat, Laboratoire de Psychologie et NeuroCognition

Publications and helpful links

General Publications

• Folstein MF, Folstein SE, McHugh PR. "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975 Nov;12(3):189-98. doi: 10.1016/0022-3956(75)90026-6. No abstract available.
• KATZ S, FORD AB, MOSKOWITZ RW, JACKSON BA, JAFFE MW. STUDIES OF ILLNESS IN THE AGED. THE INDEX OF ADL: A STANDARDIZED MEASURE OF BIOLOGICAL AND PSYCHOSOCIAL FUNCTION. JAMA. 1963 Sep 21;185:914-9. doi: 10.1001/jama.1963.03060120024016. No abstract available.
• Conway AR, Kane MJ, Bunting MF, Hambrick DZ, Wilhelm O, Engle RW. Working memory span tasks: A methodological review and user's guide. Psychon Bull Rev. 2005 Oct;12(5):769-86. doi: 10.3758/bf03196772.
• Tombaugh TN. Trail Making Test A and B: normative data stratified by age and education. Arch Clin Neuropsychol. 2004 Mar;19(2):203-14. doi: 10.1016/S0887-6177(03)00039-8.
• Lawton MP, Brody EM. Assessment of older people: self-maintaining and instrumental activities of daily living. Gerontologist. 1969 Autumn;9(3):179-86. No abstract available.
• Bartsch LM, Singmann H, Oberauer K. The effects of refreshing and elaboration on working memory performance, and their contributions to long-term memory formation. Mem Cognit. 2018 Jul;46(5):796-808. doi: 10.3758/s13421-018-0805-9.
• Belleville S, Chertkow H, Gauthier S. Working memory and control of attention in persons with Alzheimer's disease and mild cognitive impairment. Neuropsychology. 2007 Jul;21(4):458-69. doi: 10.1037/0894-4105.21.4.458.
• Camos V, Johnson M, Loaiza V, Portrat S, Souza A, Vergauwe E. What is attentional refreshing in working memory? Ann N Y Acad Sci. 2018 Jul;1424(1):19-32. doi: 10.1111/nyas.13616. Epub 2018 Mar 15.
• Inasaridze K, Foley JA, Logie RH, Sala SD. Dual task impairments in vascular dementia. Behav Neurol. 2010;22(1-2):45-52. doi: 10.3233/BEN-2009-0252.
• Zheng C, Zhang RS, Wan T, Zhao JS. Topological Alterations of Working Memory Impairment in Aged Patients With Vascular Dementia. Front Aging Neurosci. 2021 Oct 4;13:741445. doi: 10.3389/fnagi.2021.741445. eCollection 2021.
• Baddeley AD, Baddeley HA, Bucks RS, Wilcock GK. Attentional control in Alzheimer's disease. Brain. 2001 Aug;124(Pt 8):1492-508. doi: 10.1093/brain/124.8.1492.
• Belleville S, Peretz I, Malenfant D. Examination of the working memory components in normal aging and in dementia of the Alzheimer type. Neuropsychologia. 1996 Mar;34(3):195-207. doi: 10.1016/0028-3932(95)00097-6.
• Foley JA, Cocchini G, Logie RH, Della Sala S. No dual-task practice effect in Alzheimer's disease. Memory. 2015;23(4):518-28. doi: 10.1080/09658211.2014.908922. Epub 2014 Apr 30.
• Gagnon LG, Belleville S. Working memory in mild cognitive impairment and Alzheimer's disease: contribution of forgetting and predictive value of complex span tasks. Neuropsychology. 2011 Mar;25(2):226-36. doi: 10.1037/a0020919.
• Jahn H. Memory loss in Alzheimer's disease. Dialogues Clin Neurosci. 2013 Dec;15(4):445-54. doi: 10.31887/DCNS.2013.15.4/hjahn.
• Jellinger KA, Attems J. Prevalence and pathology of vascular dementia in the oldest-old. J Alzheimers Dis. 2010;21(4):1283-93. doi: 10.3233/jad-2010-100603.
• Korczyn AD, Vakhapova V, Grinberg LT. Vascular dementia. J Neurol Sci. 2012 Nov 15;322(1-2):2-10. doi: 10.1016/j.jns.2012.03.027. Epub 2012 May 8.
• McGuinness B, Barrett SL, Craig D, Lawson J, Passmore AP. Executive functioning in Alzheimer's disease and vascular dementia. Int J Geriatr Psychiatry. 2010 Jun;25(6):562-8. doi: 10.1002/gps.2375.
• O'Brien JT, Thomas A. Vascular dementia. Lancet. 2015 Oct 24;386(10004):1698-706. doi: 10.1016/S0140-6736(15)00463-8.
• Raoux N, Le Goff M, Auriacombe S, Dartigues JF, Amieva H. [Semantic and letter fluency tasks: normative data in an elderly population of 70 years old and over from the PAQUID cohort]. Rev Neurol (Paris). 2010 Jun-Jul;166(6-7):594-605. doi: 10.1016/j.neurol.2010.01.012. Epub 2010 Mar 16. French.
• Vandenberghe M, Michiels J, Vanderaspoilden V, Claes T, Fery P. [Creation and normalisation of a verbal episodic memory task in elderly adults: "GERIA-12"]. Rev Neurol (Paris). 2015 Dec;171(12):853-65. doi: 10.1016/j.neurol.2015.08.001. Epub 2015 Nov 10. French.
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• Roy, A., Fournet, N., Le Gall, D., Roulin, J. L. BRIEF. Inventaire d'évaluation comportementale des fonctions exécutive - Adaptation française. Hogrèfe France Editions (2014).
• Logie, R., Camos, V., & Cowan, N. Working memory: State of the science. Oxford University Press. (2020).
• Grober E., & Buschke H. . Genuine memory deficits in dementia. Developmental Neuropsychology,(1987) 5, 13-36.
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• Bayard, S., Erkes, J., & Moroni, C. (2009). Test du Stroop Victoria-Adaptation Francophone. CPCN-LR, Gignac.

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2024
• Primary Completion (Estimated): September 1, 2025
• Study Completion (Estimated): October 1, 2025

Study Registration Dates

• First Submitted: February 5, 2024
• First Submitted That Met QC Criteria: March 18, 2024
• First Posted (Actual): March 20, 2024

Study Record Updates

• Last Update Posted (Actual): March 20, 2024
• Last Update Submitted That Met QC Criteria: March 18, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Working memory; Alzheimer disease; Vascular dementia; Mixed dementia; Complex span task
• Additional Relevant MeSH Terms: Mental Disorders; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Tauopathies; Intracranial Arterial Diseases; Intracranial Arteriosclerosis; Leukoencephalopathies; Dementia; Alzheimer Disease; Dementia, Vascular; Mixed Dementias
• Other Study ID Numbers: 38RC23.0381

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No