Spatial Memory Training and Cognitive Function

Overview

Mild cognitive impairment (MCI) is often considered a transitional stage between normal aging and dementia, particularly Alzheimer's disease (AD). Patients with MCI have subjective memory complaints corroborated by standard neuropsychological tests but remain functionally autonomous. One of the first brain regions to show AD pathology is the hippocampus (HPC). Reduction in HPC volume is a strong predictor of AD dementia. Therefore, improvement or restoration of HPC structure and function is thus an attractive target for improvement in memory and AD prevention strategies. In the current study, the investigators propose to examine the effects of a 3-month long spatial memory program on spatial memory and the hippocampus in patients diagnosed with MCI. Neuropsychological tests are also administered before and after the training to assess the effects of the intervention on cognition. In our previous research, the investigators have shown that spatial memory intervention program (SMIP) improves cognition and hippocampal based spatial memory compared to controls.

Detailed description

The hippocampus (HPC) is a labile structure capable of neurogenesis and synaptic plasticity throughout the lifespan, which is thought to underlie its role in learning and memory, particularly of autobiographical and spatial events. Numerous studies have associated the integrity of the hippocampus with performance in way-finding. In fact, it has been demonstrated that individuals who acquired a cognitive representation of an environment with greater ease possessed more hippocampal gray matter, which was positively correlated with experience. These and other similar studies have suggested that the hippocampus' ability to process spatial memory can be modulated by experience or practice.

Studies have demonstrated increased grey matter in the HPC of both young and older human adults as a function of memory training. Interestingly, the HPC shows signs of neurogenesis across the entire lifespan and, in adult primates, this HPC neurogenesis can be stimulated through learning and memory programs that increase HPC cellular survival. Similar training programs may thus enhance HPC cellular survival in Mild Cognitive Impairment (MCI) patients by focusing on the region where the pathology first emerges. While several memory intervention studies have shown success in alleviating memory impairments in participants with subjective cognitive impairment, MCI, and in patients with Alzheimer's disease by presumably affecting the HPC, this has not yet been supported by brain imaging or assessment. By contrast, using virtual reality-based tools, the investigators have developed an innovative learning and memory program. In previous research with healthy older adults, the investigators have shown that spatial memory intervention program (SMIP) improves cognition and hippocampal-based spatial memory compared to controls. In addition, the investigators have shown a positive impact of such training on HPC grey matter. These grey matter changes in the HPC were beneficial to healthy cognition as they correlated to improvements in memory.

In the current study, the investigators propose a randomized controlled trial comparing the effects of a 12-week spatial memory intervention to an active control condition. The design will be stratified according to age, education, and sex. After an eligibility assessment at baseline, participants meeting inclusion criteria will be randomly allocated to one of the two groups with a 50% probability of being enrolled in either a spatial memory intervention or an active placebo condition. In addition, participants will be given a pre-training psychometric battery, which will be repeated twice during two post-training sessions (at one- and 26 weeks post-training) to assess cognition, daily functioning, stress, health, physical activity, quality of life, and self-esteem. The battery will also include independent computerized spatial memory tests assessing the generalization of cognitive improvement in the spatial domain, as well as paper and pencil memory tests described below.

Interventions

• Behavioral SMIP
  Participants will undergo a 3-month-long regimen of 60 minutes spatial memory training sessions held twice a week, consisting of a series of computerized virtual reality tasks.
• Other No intervention
  Control participants will not receive spatial memory intervention training. They will watch documentaries and then complete multiple choice quizzes on its content to ensure they are paying attention. The placebo condition will match the experimental condition in terms of duration and visit frequency.

Primary outcome measures

• Change in hippocampal atrophy score using SNIPE (Scoring by Non-local Image Patch Estimator) [Time frame: From study entry to Week 16 in hippocampus SNIPE grading.]

Secondary outcome measures (12)

• Hippocampal volume. [Time frame: From study entry to weeks 16 and 41.]
• Change in hippocampal atrophy score using SNIPE (Scoring by Non-local Image Patch Estimator) at 41 weeks post-study entry. [Time frame: From study entry to Week 41.]
• Changes in spatial memory performance. [Time frame: From study entry to weeks 15 and 40.]
• Changes in spatial memory performance: radial maze task. [Time frame: From study entry to weeks 15 and 40.]
• Changes in spatial memory performance: Paired arms radial maze task. [Time frame: From study entry to weeks 15 and 40.]
• Changes in spatial memory performance: Way-finding task. [Time frame: From study entry to weeks 15 and 40.]
• Changes in verbal learning performance [Time frame: From study entry to weeks 15 and 40.]
• Change in visual memory performance. [Time frame: From study entry to weeks 15 and 40.]
• Changes in general cognition. [Time frame: From study entry to weeks 15 and 40.]
• Changes in general intelligence level. [Time frame: From study entry to weeks 15 and 40.]
• Changes in selective attention performance. [Time frame: From study entry to weeks 15 and 40.]
• Changes in visuomotor working memory performance: Trail making [Time frame: From study entry to weeks 15 and 40.]

Eligibility criteria

Inclusion criteria

• Age 55 years and above.
• Primary language is English or French.
• Individuals having received a diagnosis of Mild Cognitive Impairment (MCI).

Exclusion criteria

• Self-reported having either of the following:

Current post-traumatic stress disorder and/or generalized anxiety disorder; Substance use disorder; Significant heart disease (i.e., stroke occurring during 5 years prior to study assessment or cardiac disease non-stabilized with medication); Severe Depression, or a Geriatric Depression Scale (GDS) score greater than 12; Current insomnia disorder.

• Current medications for sleep problems, or use of medications that affect sleep.
• Use of antidepressant and anti-anxiety medication for less than 3 months prior to study entry.
• Use of analgesics with codeine (or other opioids).
• Use of antipsychotic medication (past or current).
• Having undergone brain surgery or ECT.
• Self-reported colour-blindness.
• General anesthesia in the past year.
• Current smoker.
• Suspected or confirmed traumatic brain injury during the last 24 months.
• Motion sickness or intolerant to virtual reality tasks.
• Cholesterol or hypertension medication for less than 3 months or changes expected within the next 9 months.
• History or presence of neurological or psychiatric disorders (other than MCI) that in the opinion of the investigator may compromise patient safety or study objectives.
• Current severe medical conditions (e.g. untreated diabetes, cancer) that in the opinion of the investigator may compromise patient safety or study objectives.
• For female participants, severe menopausal symptoms, including hot flashes (determined from the Greene climacteric scale - any participants scoring over 15 is excluded).
• Use of computer games that are designed to help with memory or general cognition.
• Presence of any medical or psychological condition that, in the opinion of the principal investigator, may compromise the study objectives.
• Presence of contra-indications for MRI scanning.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

Canada · 1 center

• Douglas Mental Health University Institute — Verdun

Publications

• Bohbot VD, Iaria G, Petrides M. Hippocampal function and spatial memory: evidence from functional neuroimaging in healthy participants and performance of patients with medial temporal lobe resections. Neuropsychology. 2004 Jul;18(3):418-25. doi: 10.1037/0894-4105.18.3.418. PMID 15291720
• Bohbot VD, Lerch J, Thorndycraft B, Iaria G, Zijdenbos AP. Gray matter differences correlate with spontaneous strategies in a human virtual navigation task. J Neurosci. 2007 Sep 19;27(38):10078-83. doi: 10.1523/JNEUROSCI.1763-07.2007. PMID 17881514
• Iaria G, Petrides M, Dagher A, Pike B, Bohbot VD. Cognitive strategies dependent on the hippocampus and caudate nucleus in human navigation: variability and change with practice. J Neurosci. 2003 Jul 2;23(13):5945-52. doi: 10.1523/JNEUROSCI.23-13-05945.2003. PMID 12843299

Identifiers

NCT: NCT07002996 · Auto-SMIP-001 · 488505

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗