Transcranial Alternating Current Stimulation (tACS) Combined With Cognitive Training in Alzheimer's Disease (AD_tACSrehab)
Interventional Study to Evaluate the Effectiveness of Transcranial Alternating Current Stimulation (tACS) Combined With Cognitive Training on Cognitive Performance in Patients With Alzheimer's Disease
The aim of the study is to evaluate the clinical and biological efficacy, as well as predictors of efficacy, of a home-based intervention combining transcranial alternating current stimulation (tACS) with individualized computerized cognitive training in patients with mild Alzheimer's disease (AD).
In neurodegenerative diseases, including AD, neurodegeneration is accompanied by alterations in brain oscillatory activity. Restoration of these oscillations through neuronal entrainment has shown beneficial effects in animal models, while previous studies in patients with AD have demonstrated that gamma-frequency tACS applied over the precuneus is safe and well tolerated and is associated with improvements in cognitive performance and cholinergic function, as well as modulation of brain oscillatory activity. Cognitive rehabilitation may also improve memory performance in patients with mild AD. Based on this evidence, the present study investigates a multimodal approach combining gamma-tACS with individualized computerized memory training.
The study is a multicenter, randomized, placebo-controlled, double-blind trial involving 30 participants with mild AD. Participants will be randomly assigned to one of two groups: Group 1 will receive real gamma-tACS for 8 weeks (5 sessions/week, 60 minutes/session) combined with cognitive training (2 sessions/week, 30 minutes/session); Group 2 will receive sham tACS according to the same schedule, combined with the same cognitive training. tACS will be applied over the precuneus. Treatment will initially be performed in the hospital and will subsequently be administered at home under remote supervision by the study team.
Assessments will be performed at baseline (T00), after 8 weeks of treatment (T08), and at follow-up visits at 16 weeks (T16) and 24 weeks (T24) from baseline. At each time point, participants will undergo clinical and neuropsychological assessment, blood sampling, and transcranial magnetic stimulation (TMS). The occurrence of adverse events will be monitored throughout the duration of the study.
The main objectives of the study are: 1) to evaluate the short- and long-term effects of the combined intervention on cognitive performance; 2) to investigate intervention-induced changes in biological markers of neurodegeneration, inflammation, and synaptic function; 3) to evaluate the effects of the intervention on cholinergic transmission through the TMS short-latency afferent inhibition (SAI) measure; and 4) to investigate potential predictors of treatment efficacy.
Aperçu de l'étude
Statut
Les conditions
Type d'étude
Inscription (Estimé)
Phase
- N'est pas applicable
Contacts et emplacements
Lieux d'étude
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Milan, Italie
- Pas encore de recrutement
- IRCCS S. Maria Nascente - Fondazione Don Carlo Gnocchi
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Contact:
- Francesca Baglio, MD
- Numéro de téléphone: +390240308951
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Brescia
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Brescia, Brescia, Italie, 25125
- Recrutement
- IRCCS Istituto Centro San Giovanni Di Dio - Fatebenefratelli
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Chercheur principal:
- Barbara Borroni, MD
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Contact:
- Barbara Borroni, MD
- Numéro de téléphone: +39 0303501358
- E-mail: bborroni@fatebenefratelli.eu
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Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
Inclusion Criteria:
Patients:
- Male or female participants aged ≥18 years at the time of signing the informed consent form;
- Clinical diagnosis of mild Alzheimer's disease (AD) according to current clinical criteria;
- Availability of a caregiver who can assist the participant and who has successfully completed the required training for the use of the device at home.
Caregivers:
- Male or female caregivers aged ≥18 years;
- Compliance with participation in the in-hospital training;
- Mini-Mental State Examination (MMSE) score >27/30.
Exclusion Criteria:
- Age below that specified in the inclusion criteria;
- Inability to understand;
- Contraindications to tACS and TMS (e.g., presence of a cardiac pacemaker or metallic implants incompatible with electrical or magnetic fields, history of epilepsy, or current pregnancy, as assessed using the safety questionnaire).
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Tripler
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
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Comparateur factice: TACS factices
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Participants will receive individualized computerized memory training for 8 weeks (2 sessions/week, 30 minutes/session) through synchronous telerehabilitation. The memory training will be individualized based on each participant's performance on the Face-Name Association Task (FNAT) and will use an errorless learning approach. 40 at-home sessions (5 days/week for 8 weeks), each consisting of the application of sham tACS applied over the precuneus for a duration of 60 minutes each. The electrode placement will be identical to that used for real stimulation. However, the electrical current will be automatically interrupted approximately 5 seconds after the start of stimulation, making it impossible for the participant to distinguish between sham and real stimulation. |
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Expérimental: Real tACS
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40 at-home sessions (5 days/week for 8 weeks), each consisting of the application of tACS (real, 40 Hz) applied over the precuneus for a duration of 60 minutes each. Participants will receive individualized computerized memory training for 8 weeks (2 sessions/week, 30 minutes/session) through synchronous telerehabilitation. The memory training will be individualized based on each participant's performance on the Face-Name Association Task (FNAT) and will use an errorless learning approach. |
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Mini-Mental State Examination (MMSE)
Délai: Change from baseline to week 24
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The global cognitive functioning will be assessed by Mini-Mental State Examination (MMSE); MMSE scores range from 0 to 30, with higher scores indicating a more preserved cognition. |
Change from baseline to week 24
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Semantic Fluency Test
Délai: Change from baseline to week 8, 16, and 24
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Lexical-semantic access and executive functioning will be evaluated by Semantic Fluency Test. Participant is asked to generate as many words as possible from a given category within a limited time (60 seconds); higher scores indicate better performance. |
Change from baseline to week 8, 16, and 24
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Trail Making Test (TMT - A, B)
Délai: Change from baseline to week 8, 16, and 24
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Executive function will be assessed using the Trail Making Test, including Part A (visual attention and processing speed) and Part B (task switching and cognitive flexibility). Higher completion times reflect poorer performance. |
Change from baseline to week 8, 16, and 24
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Rey Auditory Verbal Learning Test (RAVLT)
Délai: Change from baseline to week 8, 16 and 24
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Verbal memory will be assessed using the Rey Auditory Verbal Learning Test (RAVLT), including immediate recall (sum of trials), delayed recall after 15 minutes. Scores reflect the number of correctly recalled items. |
Change from baseline to week 8, 16 and 24
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Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog-13)
Délai: Change from baseline to week 8, 16 and 24
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The ADAS-Cog-13 consists of 13 tasks assessing cognitive domains including memory, language, praxis, orientation, and attention. Total scores range from 0 to 85, with higher scores indicating greater cognitive impairment. |
Change from baseline to week 8, 16 and 24
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Face-Name Associative Memory Test (FNAT)
Délai: Change from baseline to week 8, 16 and 24
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The Face-Name Associative Memory Test is used to assess the participant's associative memory and is composed of encoding and retrieval phases, with higher scores indicating better function. |
Change from baseline to week 8, 16 and 24
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Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL)
Délai: Change from baseline to week 8, 16 and 24
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ADCS-ADL evaluates activities of daily living. The scores range from 0-78 with lower scores indicating more severe functional impairment. |
Change from baseline to week 8, 16 and 24
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Neuropsychiatric Inventory (NPI)
Délai: Change from baseline to week 8, 16 and 24
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Neuropsychiatric Inventory (NPI) is designed to be a structured clinical interview about neuropsychiatric and behavioral symptoms; the score ranges from 0 (no symptoms) to 144 (severe symptoms). |
Change from baseline to week 8, 16 and 24
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Clinical Dementia Rating scale - Sum of Boxes (CDR-SoB)
Délai: Change from baseline to week 8, 16 and 24
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The Clinical Dementia Rating-Sum of Boxes (CDR-SB) assesses cognitive and functional impairment across six domains: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. Total scores range from 0 to 18, with higher scores indicating greater cognitive and functional impairment. |
Change from baseline to week 8, 16 and 24
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Clinical Dementia Rating scale - Global Score (CDR-GS)
Délai: Change from baseline to week 8, 16 and 24
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The Clinical Dementia Rating Global Score (CDR-GS) assesses the overall severity of cognitive and functional impairment across six domains: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. Global scores range from 0 to 3, with higher scores indicating greater impairment. |
Change from baseline to week 8, 16 and 24
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Zarit Burden Interview (ZBI)
Délai: Change from baseline to week 8, 16, and 24
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The Zarit Burden Interview (ZBI) assesses the perceived burden experienced by caregivers of individuals with dementia. It consists of 22 items rated on a 5-point scale. Total scores range from 0 to 88, with higher scores indicating greater caregiver burden. |
Change from baseline to week 8, 16, and 24
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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Change in SAI measurements
Délai: Change from baseline to week 8, 16, and 24
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By using transcranial magnetic stimulation (TMS), the investigators will evaluate the effects of gamma tACS on short latency afferent inhibition (SAI), which is a marker of cholinergic transmission. SAI is expressed as percent of the unconditioned motor evoked potential. |
Change from baseline to week 8, 16, and 24
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Change From Baseline in Biological Marker Concentrations
Délai: Change from baseline to week 8, 16, and 24
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A venous blood draw will be performed at each timepoint. Samples will be processed for serum, plasma, and DNA extraction. Changes from baseline in biological marker concentrations, including plasma p-tau217, will be evaluated over time. |
Change from baseline to week 8, 16, and 24
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Demographic characteristics
Délai: Baseline
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Demographic characteristics (age, gender, and level of education) will be evaluated as predictors of treatment efficacy and examined for associations with differential treatment response. |
Baseline
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Baseline Clinical Dementia Rating-Sum of Boxes (CDR-SB)
Délai: Baseline
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The Clinical Dementia Rating-Sum of Boxes (CDR-SB) will be used to assess disease severity at baseline and evaluated as a predictor of treatment efficacy and examined for associations with differential treatment response. The CDR-SB assesses cognitive and functional impairment across six domains: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. Total scores range from 0 to 18, with higher scores indicating greater disease severity. |
Baseline
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Baseline Clinical Dementia Rating - Global Score (CDR-GS)
Délai: Baseline
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The Clinical Dementia Rating - Global Score (CDR-GS) will be used to assess disease severity at baseline and evaluated as a predictor of treatment efficacy and examined for associations with differential treatment response. The CDR-SB assesses cognitive and functional impairment across six domains: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. Global scores range from 0 to 3, with higher scores indicating greater impairment. |
Baseline
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Level of Education and Occupational Attainment as Proxies of Cognitive Reserve
Délai: Baseline
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Level of education and occupational attainment will be assessed at baseline as proxy measures of cognitive reserve and examined for associations with differential treatment response. |
Baseline
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Plasma Biomarker Profile
Délai: Baseline
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The plasma biomarker profile will be evaluated as a predictor of treatment efficacy and examined for associations with differential treatment response. |
Baseline
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Collaborateurs et enquêteurs
Publications et liens utiles
Publications générales
- Cummings JL, Mega M, Gray K, Rosenberg-Thompson S, Carusi DA, Gornbein J. The Neuropsychiatric Inventory: comprehensive assessment of psychopathology in dementia. Neurology. 1994 Dec;44(12):2308-14. doi: 10.1212/wnl.44.12.2308.
- Bahar-Fuchs A, Clare L, Woods B. Cognitive training and cognitive rehabilitation for mild to moderate Alzheimer's disease and vascular dementia. Cochrane Database Syst Rev. 2013 Jun 5;2013(6):CD003260. doi: 10.1002/14651858.CD003260.pub2.
- Antal A, Alekseichuk I, Bikson M, Brockmoller J, Brunoni AR, Chen R, Cohen LG, Dowthwaite G, Ellrich J, Floel A, Fregni F, George MS, Hamilton R, Haueisen J, Herrmann CS, Hummel FC, Lefaucheur JP, Liebetanz D, Loo CK, McCaig CD, Miniussi C, Miranda PC, Moliadze V, Nitsche MA, Nowak R, Padberg F, Pascual-Leone A, Poppendieck W, Priori A, Rossi S, Rossini PM, Rothwell J, Rueger MA, Ruffini G, Schellhorn K, Siebner HR, Ugawa Y, Wexler A, Ziemann U, Hallett M, Paulus W. Low intensity transcranial electric stimulation: Safety, ethical, legal regulatory and application guidelines. Clin Neurophysiol. 2017 Sep;128(9):1774-1809. doi: 10.1016/j.clinph.2017.06.001. Epub 2017 Jun 19.
- Nitsche MA, Cohen LG, Wassermann EM, Priori A, Lang N, Antal A, Paulus W, Hummel F, Boggio PS, Fregni F, Pascual-Leone A. Transcranial direct current stimulation: State of the art 2008. Brain Stimul. 2008 Jul;1(3):206-23. doi: 10.1016/j.brs.2008.06.004. Epub 2008 Jul 1.
- Costa A, Bagoj E, Monaco M, Zabberoni S, De Rosa S, Papantonio AM, Mundi C, Caltagirone C, Carlesimo GA. Standardization and normative data obtained in the Italian population for a new verbal fluency instrument, the phonemic/semantic alternate fluency test. Neurol Sci. 2014 Mar;35(3):365-72. doi: 10.1007/s10072-013-1520-8. Epub 2013 Aug 21.
- Herrmann CS, Rach S, Neuling T, Struber D. Transcranial alternating current stimulation: a review of the underlying mechanisms and modulation of cognitive processes. Front Hum Neurosci. 2013 Jun 14;7:279. doi: 10.3389/fnhum.2013.00279. eCollection 2013.
- Benussi A, Cantoni V, Cotelli MS, Cotelli M, Brattini C, Datta A, Thomas C, Santarnecchi E, Pascual-Leone A, Borroni B. Exposure to gamma tACS in Alzheimer's disease: A randomized, double-blind, sham-controlled, crossover, pilot study. Brain Stimul. 2021 May-Jun;14(3):531-540. doi: 10.1016/j.brs.2021.03.007. Epub 2021 Mar 21.
- Benussi A, Cantoni V, Grassi M, Brechet L, Michel CM, Datta A, Thomas C, Gazzina S, Cotelli MS, Bianchi M, Premi E, Gadola Y, Cotelli M, Pengo M, Perrone F, Scolaro M, Archetti S, Solje E, Padovani A, Pascual-Leone A, Borroni B. Increasing Brain Gamma Activity Improves Episodic Memory and Restores Cholinergic Dysfunction in Alzheimer's Disease. Ann Neurol. 2022 Aug;92(2):322-334. doi: 10.1002/ana.26411. Epub 2022 Jun 6.
- Davis RN, Massman PJ, Doody RS. Cognitive intervention in Alzheimer disease: a randomized placebo-controlled study. Alzheimer Dis Assoc Disord. 2001 Jan-Mar;15(1):1-9. doi: 10.1097/00002093-200101000-00001.
- Galasko D, Bennett D, Sano M, Ernesto C, Thomas R, Grundman M, Ferris S. An inventory to assess activities of daily living for clinical trials in Alzheimer's disease. The Alzheimer's Disease Cooperative Study. Alzheimer Dis Assoc Disord. 1997;11 Suppl 2:S33-9.
- Amodio P, Wenin H, Del Piccolo F, Mapelli D, Montagnese S, Pellegrini A, Musto C, Gatta A, Umilta C. Variability of trail making test, symbol digit test and line trait test in normal people. A normative study taking into account age-dependent decline and sociobiological variables. Aging Clin Exp Res. 2002 Apr;14(2):117-31. doi: 10.1007/BF03324425.
- Kujirai T, Caramia MD, Rothwell JC, Day BL, Thompson PD, Ferbert A, Wroe S, Asselman P, Marsden CD. Corticocortical inhibition in human motor cortex. J Physiol. 1993 Nov;471:501-19. doi: 10.1113/jphysiol.1993.sp019912.
- Clare L, Woods RT, Moniz Cook ED, Orrell M, Spector A. Cognitive rehabilitation and cognitive training for early-stage Alzheimer's disease and vascular dementia. Cochrane Database Syst Rev. 2003;(4):CD003260. doi: 10.1002/14651858.CD003260.
- McCue M, Fairman A, Pramuka M. Enhancing quality of life through telerehabilitation. Phys Med Rehabil Clin N Am. 2010 Feb;21(1):195-205. doi: 10.1016/j.pmr.2009.07.005.
- Clare L, Wilson BA, Carter G, Breen K, Gosses A, Hodges JR. Intervening with everyday memory problems in dementia of Alzheimer type: an errorless learning approach. J Clin Exp Neuropsychol. 2000 Feb;22(1):132-46. doi: 10.1076/1380-3395(200002)22:1;1-8;FT132.
- Williams MM, Storandt M, Roe CM, Morris JC. Progression of Alzheimer's disease as measured by Clinical Dementia Rating Sum of Boxes scores. Alzheimers Dement. 2013 Feb;9(1 Suppl):S39-44. doi: 10.1016/j.jalz.2012.01.005. Epub 2012 Aug 1.
- Massimini M, Ferrarelli F, Huber R, Esser SK, Singh H, Tononi G. Breakdown of cortical effective connectivity during sleep. Science. 2005 Sep 30;309(5744):2228-32. doi: 10.1126/science.1117256.
- Cotelli M, Calabria M, Zanetti O. Cognitive rehabilitation in Alzheimer's Disease. Aging Clin Exp Res. 2006 Apr;18(2):141-3. doi: 10.1007/BF03327429.
- Hoy KE, Bailey N, Arnold S, Windsor K, John J, Daskalakis ZJ, Fitzgerald PB. The effect of gamma-tACS on working memory performance in healthy controls. Brain Cogn. 2015 Dec;101:51-6. doi: 10.1016/j.bandc.2015.11.002. Epub 2015 Nov 12.
- Carlesimo GA, De Risi M, Monaco M, Costa A, Fadda L, Picardi A, Di Gennaro G, Caltagirone C, Grammaldo L. Normative data for measuring performance change on parallel forms of a 15-word list recall test. Neurol Sci. 2014 May;35(5):663-8. doi: 10.1007/s10072-013-1573-8. Epub 2013 Nov 12.
- Clare L, Wilson BA, Carter G, Hodges JR, Adams M. (2001). Long-term maintenance of treatment gains following a cognitive rehabilitation intervention in early dementia of Alzheimer type: a single case study. Neuropsychological Rehabilitation. 11:477-494. doi: 10.1080/09602010042000213
- Clare L, Wilson BA, Breen K, Hodges JR. (1999). Errorless learning of face-name associations in early Alzheimer's disease. Neurocase. 5:37-46. doi: 10.1080/13554799908404063
- Verma N, Beretvas SN, Pascual B, Masdeu JC, Markey MK; Alzheimer's Disease Neuroimaging Initiative. New scoring methodology improves the sensitivity of the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) in clinical trials. Alzheimers Res Ther. 2015 Nov 12;7(1):64. doi: 10.1186/s13195-015-0151-0.
- Tokimura H, Di Lazzaro V, Tokimura Y, Oliviero A, Profice P, Insola A, Mazzone P, Tonali P, Rothwell JC. Short latency inhibition of human hand motor cortex by somatosensory input from the hand. J Physiol. 2000 Mar 1;523 Pt 2(Pt 2):503-13. doi: 10.1111/j.1469-7793.2000.t01-1-00503.x.
- Rentz DM, Amariglio RE, Becker JA, Frey M, Olson LE, Frishe K, Carmasin J, Maye JE, Johnson KA, Sperling RA. Face-name associative memory performance is related to amyloid burden in normal elderly. Neuropsychologia. 2011 Jul;49(9):2776-83. doi: 10.1016/j.neuropsychologia.2011.06.006. Epub 2011 Jun 12.
- Hajos M, Boasso A, Hempel E, Shpokayte M, Konisky A, Seshagiri CV, Fomenko V, Kwan K, Nicodemus-Johnson J, Hendrix S, Vaughan B, Kern R, Megerian JT, Malchano Z. Safety, tolerability, and efficacy estimate of evoked gamma oscillation in mild to moderate Alzheimer's disease. Front Neurol. 2024 Mar 6;15:1343588. doi: 10.3389/fneur.2024.1343588. eCollection 2024.
- Cotelli M, Manenti R, Brambilla M, Petesi M, Rosini S, Ferrari C, Zanetti O, Miniussi C. Anodal tDCS during face-name associations memory training in Alzheimer's patients. Front Aging Neurosci. 2014 Mar 19;6:38. doi: 10.3389/fnagi.2014.00038. eCollection 2014.
- Clare L, Wilson BA, Carter G, Roth I, Hodges JR. Relearning face-name associations in early Alzheimer's disease. Neuropsychology. 2002 Oct;16(4):538-47. doi: 10.1037//0894-4105.16.4.538.
- Cappa SF, Benke T, Clarke S, Rossi B, Stemmer B, van Heugten CM; European Federation of Neurological Societies. EFNS guidelines on cognitive rehabilitation: report of an EFNS task force. Eur J Neurol. 2003 Jan;10(1):11-23. doi: 10.1046/j.1468-1331.2003.00537.x.
- Cantoni V, Casula EP, Tarantino B, Cupidi C, Huber N, Altomare D, Premi E, Zummo E, Esposito R, Leonardi C, Herukka SK, Solje E, Ferrari A, Cotelli MS, Gasparotti R, Martorana A, Fracassi C, Santarnecchi E, Koch G, Haapasalo A, Grassi M, Benussi A, Borroni B. Home-Based Gamma Transcranial Alternating Current Stimulation in Patients With Alzheimer Disease: A Randomized Clinical Trial. JAMA Netw Open. 2025 Dec 1;8(12):e2546556. doi: 10.1001/jamanetworkopen.2025.46556.
- Benussi A, Grassi M, Palluzzi F, Koch G, Di Lazzaro V, Nardone R, Cantoni V, Dell'Era V, Premi E, Martorana A, di Lorenzo F, Bonni S, Ranieri F, Capone F, Musumeci G, Cotelli MS, Padovani A, Borroni B. Classification Accuracy of Transcranial Magnetic Stimulation for the Diagnosis of Neurodegenerative Dementias. Ann Neurol. 2020 Mar;87(3):394-404. doi: 10.1002/ana.25677. Epub 2020 Jan 23.
- Backman L, Dixon RA. Psychological compensation: a theoretical framework. Psychol Bull. 1992 Sep;112(2):259-83. doi: 10.1037/0033-2909.112.2.259.
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude (Estimé)
Achèvement primaire (Estimé)
Achèvement de l'étude (Estimé)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Réel)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
- Maladies du cerveau
- Maladies du système nerveux central
- Maladies du système nerveux
- Les troubles mentaux
- Troubles neurocognitifs
- Démence
- Tauopathies
- Maladies neurodégénératives
- Maladie d'Alzheimer
- Thérapeutique
- Disciplines et activités comportementales
- Thérapie de stimulation électrique
- Thérapie convulsive
- Thérapies somatiques psychiatriques
- Électrochoc
- Techniques psychologiques
- Stimulation de courant direct transcrânien
Autres numéros d'identification d'étude
- AD_tACSrehab
Informations sur les médicaments et les dispositifs, documents d'étude
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