Alisa G. Woods, PhD

People with Alzheimer disease and even mild cognitive impairment may be dangerous to themselves or others on the road. Assessments of driving ability could be useful for evaluating whether or not people with impaired cognition should in fact drive at all.

A new study out of Toronto provides more information about driving ability in the cognitively impaired and how it can be assessed. The recent report appeared in the Journal of Alzheimer’s Disease.

The investigators, led by Megan Hird of the Neuroscience Research Program, St. Michael’s Hospital, Toronto, Canada, wanted The scientists performed a systematic review of the literature and meta-analysis of driving assessment methods. These included actual on-road driving, cognitive tests, and driving simulations. They assessed the predictive ability of the tests as well as specific areas of driving impairment in these individuals.

The review and meta-analysis included a total of 32 articles, including 1,293 subjects with Alzheimer disease, 92 subjects with mild cognitive impairment, and 2,040 healthy controls. Researchers used several different outcome measurements to test for driving ability, including on-road test scores, pass/fail classifications, errors; caregiver reports; real world crash involvement; and driving simulator collisions/risky behavior.

The study authors identified several statistically significant predictors of driving performance. These included global cognition, visuospatial function, attention, and executive function. Two tests were the most effective for predicting driving performance: the Trail Making Test part B and the Maze test. In the Trail Making Test part B, a subject is required to connect alternating encircled numbers and letters. The test measures visual attention and the ability to switch tasks. In the Maze test a subject draws through mazes of increasing complexity, without back-tracking. It is designed to measure planning and foresight.

The scientists further discovered that even people with very mild Alzheimer disease are more likely to fail a driving test compared to healthy control subjects.

Overall, Hird and colleagues concluded that, “The driving ability of patients with MCI and AD appears to be related to degree of cognitive impairment. Across studies, there are inconsistent cognitive predictors and reported driving outcomes in MCI and AD patients.”

Although the meta-analysis and systematic review provides some information about driving ability and cognition, more studies with greater specificity are still needed. For example, the effect of mild cognitive impairment on driving is not yet clear, possibly because studies of driving tend to focus more on Alzheimer disease-notable by the lower total subjects with mild cognitive impairment assessed in this meta-analysis compared to those with Alzheimer disease.

The authors also suggest that specific subject characteristics need to be assessed, namely “Future large-scale studies should investigate the driving performance and associated neural networks of subgroups of AD (very mild, mild, moderate) and [mild cognitive impairment] (amnestic, non-amnestic, single-domain, multiple-domain).”

Further prospective clinical trials may aid in the development of cognitive tests that can assess whether or not an impaired individual should drive. According to the American Academy of Neurology (AAN) 

, a mini mental State Exam of 24 or less can indicate risk for unsafe driving. AAN guidelines also note that caregivers may be best to assess whether or not an individual with Alzheimer should drive. Future studies may concentrate on the predictive ability of direct cognitive tests, along with caregiver assessments.

A systematic review and meta-analysis of on-road simulator and cognitive driving assessment in Alzheimer's disease and mild cognitive impairment

Articles

Investigators questioned whether cognitive tests could predict driving ability in people with Alzheimer disease and mild cognitive impairment.

Driving with Cognitive Impairment

A new study from researchers in Texas and Alabama suggests that a busy lifestyle in older adults could help improve and sustain memory. The research report appeared in the journal 

Prior research suggests that performing mentally challenging tasks can help older adults retain memory, but what about those individuals who are busy as part of their general lifestyle?

“We were surprised at how little research there was on busyness, given that being too busy seems to be a fact of modern life for so many,” noted Denise Park, one of the study authors.

Led by Sara B. Festini of the School of Behavioral and Brain Sciences, University of Texas at Dallas, the investigators wanted to test the effects of an engaged lifestyle on cognition. They studied 330 adults between the ages of 50 to 89 who were participants in the 

 The DLBS is a large research project that aims to study the healthy brain in adults, in the decades from age 20 to 90. More than 500 individuals enrolled in the study, and they are evaluated every four years.

In this particular sub-analysis of the DLBS, subjects completed several tests, including of working and long-term memory, reasoning, and crystallized knowledge (such as vocabulary). The cognitive tests were given over 2 days, in 2- to 3-hour sessions per day.

Martin and Park Environmental Demands Questionnaire (MPED)

. This is a self-report instrument designed to measure day-to-day events experienced by adults between the ages of 35 to 84. The busyness assessment included questions such as “How busy are you during an average day? How often do you have too many things to do each day to actually get them all done? How often do you have so many things to do that you go to bed later than your regular bedtime?” Participants rated each question on a scale of 1-5.

Overall, Festini and colleagues found that greater busyness corresponded with better cognition.  They measured the greatest effects for episodic memory; including knowledge of events, times, and places. Busy individuals also had better processing speed for memory, and superior working memory, reasoning, and crystallized knowledge.

The correspondence of busyness and better cognition was consistent in adults of all ages, from 50-89. Other research studies have shown that new learning retains neurons in the hippocampus, which the authors suggested as one possible mechanism for the results observed. The hippocampus processes episodic memory in particular, as well as the transition of short-term to long-term memory.

The authors noted, however, that the results are a correlation, so it is not clear whether busyness improves cognitive or if people with better mental abilities tend to engage in more activities. In their published report they noted “Although correlational in nature, these results are in line with an engagement framework, and they have implications for the usefulness of engagement training programs. Additional experimental work should be conducted to determine if manipulations of busyness influence cognition in a similar manner.”

Future studies from this research group may focus on whether cognition improves in people who increase their activity and which types of activities are most useful.

Festini and colleagues emphasized the likely benefits of an active lifestyle, noting “Overall, our findings offer encouragement to maintain active, busy lifestyles throughout middle and late adulthood.”

The busier the better: greater busyness is associated with better cognition

Did an active schedule help or hinder cognitive skills such as memory, reasoning, and crystallized knowledge in a group of adults aged 50-89 years?

Does a Busy Lifestyle Improve Memory?

In a mouse model of stroke, Johns Hopkins researchers have found that intrinsic nervous system repair mechanisms could allow mice to recover more quickly. Specifically, mice partially lost the use of their front paws following an initial stroke, but were able to successfully grab food pellets after a second stroke.

The research appeared in the online journal 

The scientists first trained animals to perform a grasping task then gave them a stroke using photocoagulation. After 7 days, the animals were retrained in the reaching task, for a total of nineteen days. The animals did not fully recover, and were given a second stroke. The researchers then retrained the animals in the reaching task after only one day post-recovery, for a total of nine days. The animals fully recovered to normal performance following the second stroke.

The findings build upon the idea that neurons may have more plasticity, i.e., capacity for repair in adulthood, than previously believed.

The authors noted in their report that the findings in no way suggest that inducing a stroke is a viable treatment option. However, the findings do open up the intriguing possibility that the nervous system has intrinsic repair mechanisms that could be exploited. If the mechanisms mediating repair after a second stroke could be uncovered, this might open up new avenues for stroke treatments and for the prevention of neural damage following stroke.

“If we can better understand how to reopen or extend the optimal recovery period after a stroke, then we might indeed change how we treat patients for the better,” remarked Steven Zeiler, MD, PhD, in a press release. Zeiler is an assistant professor of neurology at the Johns Hopkins University School of Medicine. “Our study adds new strong and convincing evidence that there is a sensitive period following stroke where it’s easiest to relearn motor movements - a topic that is still debated among stroke researchers” he added.

The research is a follow-up to a prior Johns Hopkins study, which identified the first seven days as the optimal recovery time following induced stroke in mice.

 However, in this study the scientists were able to extend the stroke recovery window by giving animals the antidepressant fluoxetine right after the stroke. Because fluoxetine works as a serotonin reuptake inhibitor, the effects observed could be due to actions on the serotonergic system.

The antidepressant increased the animals’ ability to learn the same pellet-grabbing task. However, the study did not show that it could be possible to reopen the learning period. These new results suggest that learning can indeed occur again.

In their study report, the investigators concluded “New ischemia can reopen a sensitive period of heightened responsiveness to training and mediate full recovery from a previous stroke.”

The research could have implications for recovery of function in individuals who have suffered more than one stroke. However, at present the results have only been observed in an animal model. Further investigations of recovery of function following stroke and the mechanisms underlying it need to be conducted in humans.

Paradoxical motor recovery from a first stroke after induction of a second stroke: reopening a postischemic sensitive period

. Neurorehabil Neural Repair. 2015 Dec 31.

Research in mice shows potential value of common antidepressant in stroke victims too sick for immediate rehab

New research in a mouse model could have implications for recovery of function in individuals who have suffered more than one stroke.

Can Stroke Initiate New Neurological Repair Mechanisms?

Researchers at Brigham and Women’s Hospital (BWH) and the National Institute of Neurological Disorders and Stroke (NINDS) have initiated a new project to identify those at risk for multiple sclerosis (MS).

“By focusing on first-degree family members of MS patients, the research team seeks to better understand the sequence of events that leads some people to develop the disease. Their work also sets the stage for developing and testing interventions with which to block the onset of MS.”

The scientists introduced the Genes and Environment in Multiple Sclerosis (GEMS) project via a new report published in the Annals of Neurology.

 The investigators will assess risk using both genetic and environmental assessments in 2632 first-degree relatives of people with MS residing in the United States.

“This first report from the GEMS study is important because it shows that we can recruit the large number of family members that is necessary to perform a well-powered study of MS risk factors,” noted first author Zongqi Xia, PhD, of BWH’s Ann Romney Center for Neurologic Diseases.

In the initial analysis, the researchers found a subset of family members that may be at higher risk for MS. The risk factor assessment could help identify those individuals who might be most likely to develop MS, although further work is needed to refine the MS risk algorithm.

“Early detection of MS means the possibility of earlier treatment, which could delay the accumulation of disability,” remarked author Phil De Jager, MD, PhD, Director of the Program in Translational NeuroPsychiatric Genomics at the Ann Romney Center for Neurologic Diseases at BWH. “Our long-term goal is to map out the sequence of events leading from health to disease, in order to be able to identify and intervene early in individuals at high-risk of MS,” he added.

Recruitment has been accomplished through both patient advocacy groups including the National Multiple Sclerosis Society, as well as through Facebook. A 

 has been set up as well, through which the public can gain information about the study. A total enrollment of 5000 first-degree relatives is planned, with the project continuing for the next 20 years.

Several measurements are being collected for the study, including a medical history questionnaire, family history, and exposures from the environment, as well as saliva collection for DNA analysis.

“Since the disease likely starts many years before the first symptom appears, we do not yet understand how genetic and environmental risk factors come together to trigger MS,” stated co-senior author Daniel Reich, MD, PhD, of the Division of Neuroimmunology and Neurovirology at the NINDS. “When a patient comes to see a neurologist for the first time, the process of brain inflammation is well underway, since many lesions have few or no symptoms.”

The initial report and overall project could greatly help in assessing risk and facilitating prevention of MS.

“This report is an important first step. We do not yet have a tool that we can use clinically to predict MS. To develop such tools further, and to develop a platform for testing strategies to prevent the disease altogether, we are expanding GEMS into a larger collaborative study that will accelerate the progress of discovery and bring together a community of investigators to overcome this important challenge,” says De Jager. “Overall, the risk of MS remains very small for most family members. The most effective therapies for MS will ultimately be those that prevent its onset, as halting inflammation and disease progression are much more difficult once the disease has become established.”

Genes and environment in multiple sclerosis project: a platform to investigate multiple sclerosis risk

2. EurekAlert. Predicting who will develop multiple sclerosis. 8 Feb 2016. 

http://www.eurekalert.org/pub_releases/2016-02/bawh-pww020816.php

By studying first-degree relatives of patients with MS, can researchers perfect a risk algorithm for the disease?

Alisa G. Woods, PhD

Articles

Driving with Cognitive Impairment

Does a Busy Lifestyle Improve Memory?

Can Stroke Initiate New Neurological Repair Mechanisms?

Predicting Multiple Sclerosis Risk: GEMS Project