By Jessica Orner, MD

Family Medicine Physician, Special Interest: Integrative Medicine, LGHP Family Medicine Quentin, Lebanon, PA

Dr. Orner reports no financial relationships relevant to this field of study.

SYNOPSIS: Progressive aerobic exercise training appears to be a low-risk and effective intervention for improving cognitive function in community-dwelling adults with mild subcortical ischemic vascular cognitive impairment.

SOURCE: Liu-Ambrose T, Best JR, Davis JC, et al. Aerobic exercise and vascular cognitive impairment: A randomized controlled trial. Neurology 2016;87:2082-2090.

Cognitive impairment affects an estimated 16 million people in the United States. Dementia affects between 2.4-5.5 million, with approximately 1 million new cases projected per year.1 Cognitive decline and dementia are common concerns among older adults and can place significant financial and emotional burdens on many families. In 2012, the total healthcare cost for dementia was approximately $200 billion annually, not including the estimated $210 billion from informal care givers.1 With all these concerns, there is increasing research on preventive treatment options for cognitive impairment. Generally, cognitive impairment is a limitation in mental functioning. Cognitive impairment can be divided into areas such as mild cognitive impairment and dementia. Whereas mild cognitive impairment does not affect independent activities of daily living (IADL), dementia is defined as a decline in at least two of five cognitive domains (memory, attention, language, praxis, and executive functioning) not due to another medical or psychiatric condition and that affects IADLs.1

This article focused on subcortical ischemic vascular cognitive impairment (SIVCI), a subset of vascular cognitive impairment. Although vascular dementia is the second most common cause of dementia, SIVCI is the most common form of vascular dementia.2 With the criteria used in this study, the participants were classified as exhibiting mild cognitive impairment with a high risk of developing dementia.

In this proof-of-concept, blind, randomized, controlled trial, the researchers examined the role of a progressive exercise training program on cognitive and functional symptoms in adults with mild SIVCI. The researchers considered a proof-of-concept study because of its small size and preliminary evidence of efficacy. They also believed that application of biomarkers would be useful to evaluate the role of exercise in cognitive functioning more rigorously.2

Participants included adults with a clinical diagnosis of mild SIVCI based on the presence of small vessel ischemic disease and cognitive syndrome. Small vessel ischemic disease was defined as evidence of neurologic signs consistent with subcortical brain lesions and evidence of cerebrovascular disease on brain MRI or CT. Cognitive syndrome was defined as a Montreal Cognitive Assessment (MoCA) score < 26/30 and a Mini-Mental Status Examination (MMSE) ≥ 20 at the initial screening.2

Study participants were randomized to progressive aerobic training for six months or usual care with education on vascular cognitive impairment. Participants were assessed at baseline, after six months of intervention, and six months after formal cessation of aerobic training.2 The aerobic training involved thrice-weekly classes lasting 60 minutes: 10-minute warm-up, 40-minute walk, and 10-minute cool down. The intensity of the program was monitored using heart rate, the Borg Rating of Perceived Exertion, and the “talk test.” The talk test was defined as starting at a pace that allowed comfortable conversation and progressing to a pace at which conversation was difficult.2 The initial intensity of 40% of age-specific target heart rate increased to 60-70% over the first 12 weeks of therapy, with a goal of 65%. Once at that goal, it was sustained for the remainder of the intervention period. If patients were on a beta-blocker, the subjective measures were given priority.

Study participants in the usual care with education group received monthly phone calls from research staff and education materials about vascular cognitive impairment and healthy nutrition. Based on the article, it is unclear if the aerobic training group also received educational materials.

For assessment, the researchers chose to assess cognitive performance primarily, global executive functions, and performance on ADL. The Alzheimer’s Disease Assessment Scale-Cognitive (ADAS-Cog), Executive Interview (EXIT), and Alzheimer’s Disease Cooperative Study-Activities of Daily Living (ADCS-ADL), respectively, were chosen as the assessment tools. Secondary outcomes included: six-minute walk test, body mass index, resting heart rate, and blood pressure. Seventy-one individuals were recruited, of which 70 were included in the analyses. One participant was deemed ineligible because of a diagnosis of mixed dementia.

At six months, there were statistically significant differences in the ADAS-Cog performance (-1.71 point difference; 95% confidence interval [CI], -3.15 to -0.26; P = 0.02), six-minute walk test (30.35 meter difference; 95% CI, 5.82-54.86; P = 0.02), and diastolic blood pressure (-6.89 mmHg difference; 95% CI, -12.52 to -1.26; P = 0.02), which decreased and were no longer significant by the six-month post-intervention assessment. No statistically significant differences were observed for EXIT or ADCS-ADL at the end of the intervention or six months post-intervention. There were three adverse events, all of which were falls. Two occurred in the aerobic training group and one in the usual care group.

Compliance and feasibility were assessed during the study. The researchers determined that the intervention would be feasible if the following conditions were met:

  1. Recruitment rate > 15%;
  2. Withdrawal rate < 15%;
  3. Average aerobic training class compliance of 60%.

The observed recruitment rate via telephone was 16%, while in person, the rate was 85%. The withdrawal rate was 10% in the overall sample, with 17% in the usual care group and 3% in the intervention group. Compliance with the aerobic training group was measured through attendance and was 68%.

The authors noted several concerns and possible pitfalls. As mentioned above, the positive cognitive effects of progressive aerobic training dissolved by the six-month post-intervention re-evaluation.2 The reason for this was unclear. Further studies are needed to determine ways to improve compliance and if sustaining the regimen would leave positive effects intact. The authors mentioned that there may be a more sensitive tool for detecting modest changes in cognition, such as Vascular dementia Assessment Scale-cognitive (VADAS-Cog) instead of ADAS-Cog, but there were not enough data on these tools at the time of their intervention.2

COMMENTARY

This study suggests that progressive aerobic exercise therapy can improve cognitive function in mild sub-cortical ischemic vascular cognitive impairment. It is a low-risk intervention provided the participant can exercise safely. It is also feasible to provide in the community setting.

Accessing instructors for progressive exercise therapy may be difficult in some areas. However, clinicians could calculate the goal heart rate and instruct patients on how to take their pulse and perform the talk test when exercising, provided their cognitive impairment does not affect understanding of the tasks. It may be useful to elicit the help of the patient’s support system.

Vascular cognitive impairment is second to Alzheimer’s disease as the most common cause of dementia. The improvements in ADAS-Cog correlated with decreased diastolic blood pressure, and this may be a way in which aerobic exercise improved cognition in those with mild SIVCI.2 It would be interesting to see if the results could be generalizable to people with other types of dementia, including Alzheimer’s disease, and non-community dwelling elders, such as those in nursing facilities.

It is also notable that many of the assessment tools were not created specifically to study vascular cognitive impairment. The ADAS-Cog is designed to measure cognitive areas that are seen to decline in Alzheimer’s disease.3 It is the most commonly used cognitive testing instrument for measuring cognitive change in dementia studies.3 It consists of 11 parts and assesses cognitive functions, such as praxis, learning, and memory. However, studies show that ADAS-Cog is more precise for measuring the severity of cognitive dysfunction than the MMSE most used in the clinical setting.4

Designed to be administered by trained personnel, the EXIT is a 25-item questionnaire that assesses executive cognitive dysfunction in patients with mild dementia. ADCS-ADL is available in two versions: a 19-item version for patients with more severe dementia and a 23-item version for the assessment of ADLs in mild to moderate dementia.5 The 23-item version was used for this study.

Although this study is promising for the possibility of using exercise training for treatment of cognitive impairment, more evidence is needed on the role of exercise in the prevention of dementia or cognitive decline.6

REFERENCES

  1. Lin JS, O’Connor E, Rossom RC, et al. Screening for cognitive impairment in older adults: An evidence update for the U.S. Preventive Services Task Force. Available at: http://bit.ly/2EBt2z5. Accessed Dec. 30, 2017.
  2. Liu-Ambrose T, Best JR, Davis JC, et al. Aerobic exercise and vascular cognitive impairment: A randomized controlled trial. Neurology 2016;87:2082-2090.
  3. Connor DJ, Sabbagh MN. Administration and scoring variance on the ADAS-Cog. J Alzheimers Dis 2008;15:461-464.
  4. Balsis S, Benge JF, Lowe DA, et al. How do scores on the ADAS-Cog, MMSE, and CDR-SOB correspond? Clin Neuropsychol 2015;29:1002-1009.
  5. Robert P, Ferris S, Gauthier S, et al. Review of Alzheimer’s disease scales: Is there a need for a new multi-domain scale for therapy evaluation in medical practice? Alzheimers Res Ther 2010;2:24.
  6. Barreto PS, Demougeot L, Vellas B, Rolland Y. Exercise training for preventing dementia, mild cognitive impairment, and clinically meaningful cognitive decline: A systematic review and meta-analysis. J Gerontol A Biol Sci Med Sci 2017; Dec. 5. doi:10.1093/gerona/glx234. [Epub ahead of print].