Working Memory Functioning in Alzheimer's Disease and Vascular Dementia

Alzheimer Disease Clinical Trial

— MEMTRAV-COG  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06321380
• Other study ID #: 38RC23.0381
• Status: Not yet recruiting
• Start date: April 2024
• Est. completion date: October 2025

Study information

• Verified date: March 2024
• Source: University Hospital, Grenoble
• Contact: Amelie Bichon
• Phone: 0476728161
• Email: abichon[@]chu-grenoble.fr
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 120
• Est. completion date: October 2025
• Est. primary completion date: September 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 65 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Alzheimer Disease
• Dementia
• Dementia, Vascular
• Vascular Dementia

Intervention

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.

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 .
• 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)

Locations

Country	Name	City	State
n/a

Sponsors (5)

Lead Sponsor	Collaborator
University Hospital, Grenoble	Centre National de la Recherche Scientifique, France, Laboratoire de Psychologie et NeuroCognition, Université Savoie Mont Blanc, University Grenoble Alps

References & Publications (27)

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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. — View Citation

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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. — View Citation

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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. — View Citation

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Vergauwe E, Ricker TJ, Langerock N, Cowan N. What do people typically do between list items? The nature of attention-based mnemonic activities depends on task context. J Exp Psychol Learn Mem Cogn. 2019 May;45(5):779-794. doi: 10.1037/xlm0000625. Epub 2018 Jul 19. — View Citation

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. — View Citation

* Note: There are 27 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Processing performance in the Working memory task	Percentage of correct response in the spatial part of working memory task	15 minutes
Primary	Reaction time	Reaction time for each distractor (in ms) in the spatial part of working memory task	30 minutes
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Stroop Test - denomination part	the denomination part of stroop test measures processing speed time is taken, in seconds	30 secondes
Secondary	Stroop Test - minor interference part (Time)	this part of stroop test measures low inhibition process time is taken, in seconds	30 secondes
Secondary	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
Secondary	Stroop Test - major interference part (time)	this part of stroop test measures strong inhibition process time is taken, in seconds	90 secondes
Secondary	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
Secondary	Trail Making Test - Part A (time)	This test evaluate motor speed processing Time in seconds	2 minutes
Secondary	Trail Making Test - Part A (errors)	This test evaluates motor speed processing Number of errors is noted	2 minutes
Secondary	Trail Making Test - Part B (time)	This test evaluates mental flexibility Time in seconds	5 minutes
Secondary	Trail Making Test - Part B (errors)	This test evaluates mental flexibility Number of errors is noted	5 minutes
Secondary	Category fluences	Number of correct words is noted	5 minutes
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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