Low Dose Ionizing Radiation Using CT Scans as a Potential Therapy for Alzheimer's Dementia: A Pilot Study

Study Overview
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Brief Summary
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The goal of this project is to determine whether low doses of ionizing radiation (LDIR) from repeat CT scanning improves function, cognition and/or behavior in severe AD.

Detailed Description
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Alzheimer's dementia (AD) is a disorder of uncertain cause and pathogenesis that primarily affects older adults. It accounts for more than 50 percent of cases of dementia in the elderly and is a leading source of morbidity and mortality in the aging population. The most essential and often earliest symptom is selective memory impairment. While treatments can improve some symptoms, there is no cure or disease-modifying therapy, and the disease inevitably progresses in all patients. The mainstay of management is still symptomatic treatment of behavioral disturbances, environmental manipulations to prevent behavioural disturbances, and counseling with respect to safety issues. The goal of this project is to determine whether low doses of ionizing radiation (LDIR) from repeat CT scanning improves function, cognition and/or behavior in severe AD. This is based upon the treatments given in 2015 to a patient in hospice in the USA with advanced AD. On July 23, she received two CT scans of her brain. Two weeks later she received a third CT scan, and two weeks after this, a fourth CT scan. She partially improved and was discharged to an Alzheimer care home. In terms of the mechanism whereby CT scanning might lead to improvement, reactive oxygen species (ROS) are produced abundantly and constantly by aerobic metabolism in all organisms, damaging biomolecules including those in the brain. AD is postulated to be caused by the accumulation of oxidative stress damage in the brain that was not prevented, repaired or removed by the patient's own biological protective mechanisms. These systems, characterized genetically, operate against all toxins regardless of whether they are produced endogenously or by external physical, chemical or biological agents. As people age, their protection systems become progressively weaker. LDIR is postulated to stimulate adaptive protection systems. This may produce beneficial effects including improvement in AD symptoms. With about three-quarters of human tissue being water, most of the initial radiation-induced damage is radiolysis of water, producing ROS and hydrogen peroxide (H2O2). LDIR leads to mild oxidative stress and strong signaling, which up-regulates protection.The degree of stimulation likely depends upon individual genetic factors. CT scans are approved for clinical diagnostic imaging. Approval will be requested from the Research Ethics Board (REB) at Baycrest Health Sciences and from Health Canada to use CT scanning for the experimental treatment of AD. If this pilot study is successful, i.e., if improvement is observed in the participants, then a proposal will be prepared for more comprehensive clinical studies of this novel treatment.

Official Title
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Low Dose Ionizing Radiation Using CT Scans as a Potential Therapy for Alzheimer's Dementia (LDIR-CT-AD) Trial: A Pilot Study

Conditions
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Dementia Alzheimers

Intervention / Treatment
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* Radiation: CT scan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females with severe AD dementia (MMSE<12) between the ages of 70 to 90 years. Meet the criteria of AD (NIA-AA). If on any of the following medications: acetylcholinesterase inhibitors and/or memantine, participants must be on a stable dose for at least 60 days. Clinically stable for at least 3 months. Exclusion Criteria: Current or past history of malignancy. Previous history of radiotherapy. Neurological disorder other than AD. Currently receiving other experimental treatments. Clinical or imaging evidence of stroke (with more than 1-2 lacunar infarcts on CT scan or MRI). Major depression, bipolar affective disorder or psychosis.

Ages Eligible for Study
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Minimum Age: 70 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CT scan subjects<br>Three participants with severe Alzheimer's dementia will be studied | Radiation: CT scan<br>* Participants will receive the first LDIR treatment in one session on the same day, i.e., two CT scans of the brain that delivers a total X-ray dose (CTDIvol)10 of about 80 mGy. Participants will then be transported back to Baycrest Health Sciences. Participants will receive another LDIR treatment, i.e. a single CT scan of the brain (40 mGy), 2 weeks after the first session. They will receive a third LDIR treatment, i.e., a single CT scan of the brain (40 mGy), 2 weeks after the second session. Date, time and X-ray dose will be recorded for each participant and sent to their family physician for entry into in their health record.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Alzheimer Disease Functional Assessment and Change Scale (ADFACS) | is a specific scale for the functional assessment of people with Alzheimer Disease. A number of specific descriptions of performance levels for each item is offered, and the caregiver is asked to identify the one that most accurately describes the patient's performance . The scale consists of 16 items for the assessment of ADL, i.e. 6 items for BADL, 10 for IADL. items are scored from 0 to 4: 0 = no impairment, 1 = mild impairment, 2 = moderate impairment, 3 = severe impairment and 4 = nonassessable, with a range from 0 to 30. BADL items are scored from 0 to 5: 0 = no impairment, 1 = mild impairment, 2 = moderate impairment, 3 = severe impairment, 4 = very severe impairment and 5 = nonassessable, with a range from 0 to 24. In each part, the 'nonassessable' answer is substituted by an estimation from the average of the responded items. The total score (IADL + BADL) ranges from 0 to 54 (from best to worst). | 20 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Severe Impairment Battery (SIB) | to assess cognition | 30 minutes | 
| Cohen-Mansfield Agitation Index (CMAI) | The Cohen-Mansfield Agitation Index (CMAI) is a caregivers' rating questionnaire consisting of 29 agitated behaviours, each rated on a 7-point scale of frequency. It assesses the frequency of agitated behaviours in elderly persons in the long-term care setting. | 30 minutes |