Cognitive Rehabilitation Strengthens Brain Connections

There is increased interest in brain and cognitive rehabilitation to treat people with mild thinking and memory problems. Parkinson’s disease, while typically viewed as a neurodegenerative motor disorder, also affects thinking and memory. In a small clinical trial with Parkinson’s disease patients, patients received either occupational therapy or cognitive rehabilitation. Those who had cognitive rehabilitation showed increases in functional connectivity (a measure of time-linked correlations between changes in blood flow in different parts of the brain) between the left inferior temporal lobe and the left and right dorsolateral prefrontal cortex. These are brain areas important for a number of cognitive functions including memory, planning, and mental manipulation of information. Those who did not receive cognitive intervention did not have increases in connectivity.

What does this mean for Parkinson’s disease and for cognitive rehabilitation? It’s difficult to say with this small study. It’s also unknown how long the changes last. Without a restructuring of the brain and continued cognitive rehabilitation it is not likely that the effects will last more than weeks or months after the rehabilitation ends.

To expand on this study (to bring in other research) and put things in simple terms, if people want to protect their brains they best they can as they age, they need to remain physically and mentally active and in good physical and mental shape. Learn new things. Travel to new locations. Take up a physically demanding hobby or dedicated exercise. This won’t solve all our aging problems but it will help a lot.

Reference

Díez-Cirarda, M., Ojeda, N., Peña, J. et al. Brain Imaging and Behavior (2016). doi:10.1007/s11682-016-9639-x

Memory Problems in Some With Parkinson’s Disease

From a recent news release by Jill Pease at the University of Florida.

Using a combination of neuropsychological testing and brain imaging, University of Florida researchers have discovered that in a group of recently-diagnosed patients with Parkinson’s disease, about one quarter have significant memory problems.

Parkinson’s disease is commonly known as a movement disorder that leads to tremors and muscle rigidity, but there is growing recognition of cognitive problems associated with the disease. One of the most common is slower thinking speed that causes patients to have trouble quickly retrieving information. The UF study identifies a subset of patients who have a different kind of cognitive issue — memory problems, or difficulty learning and retaining new information.

The findings were published July 24 in the journal PLOS ONE.

“While a large proportion of people with Parkinson’s will experience slower thinking speed, which may make them less quick to speak or have difficulty doing two things at once, we now know that there are a subset of individuals with Parkinson’s disease who have memory problems,” said Catherine Price, Ph.D., the study’s senior author and an associate professor in the UF College of Public Health and Health Professions’ department of clinical and health psychology, part of UF Health. “It is important to recognize which people have issues with learning and memory so we can improve diagnostic accuracy and determine if they would benefit from certain pharmaceutical or behavioral interventions.”

For the UF study, 40 people in the early stages of Parkinson’s disease and 40 healthy older adults completed neuropsychological assessments and verbal memory tests.

About half the participants with Parkinson’s disease struggled with an aspect of memory, such as learning and retaining information, or recalling verbal information, said lead author Jared Tanner, Ph.D., an assistant research professor in the UF department of clinical and health psychology who conducted the study as part of his dissertation research for a UF doctoral degree in clinical psychology.

“And then half of those participants, or nearly one quarter of all participants with Parkinson’s, were really having a difficult time consistently with their memory, enough that it would be noticeable to other people,” said Tanner, adding that researchers were encouraged by the fact that most participants in the initial stages of Parkinson’s were not having significant memory problems.

All participants received brain scans, which used new imaging techniques that allowed the scientists to navigate the pathways of white matter fibers, the tissue through which messages travel across the brain. The methodology was developed by the research group ofThomas Mareci, Ph.D., a professor of biochemistry and molecular biology in the UF College of Medicine, and is described in a paper published July 14 in PLOS ONE.

Experts have theorized that cognitive problems in Parkinson’s are caused by a shortage of the brain chemical dopamine, which is responsible for patients’ motor issues. But with the help of imaging, the UF researchers were able to spot changes in the brain’s gray and white matter that appear unrelated to dopamine loss and are specific to those patients with Parkinson’s who have memory problems.

“Not only is gray matter important for memory, in Parkinson’s disease white matter connections between the temporal lobe and a region in the posterior portion of the brain called the retrosplenial cortex were particularly important in the recall of verbal information,” Tanner said. “People with Parkinson’s disease who had stronger connections between these areas of the brain did better at remembering information.”

Tanner’s study is part of a larger research project supported by a $2.1 million grant from the National Institute of Neurological Disorders and Stroke of the National Institutes of Health. Researchers led by Price are using imaging and cognitive testing to determine profiles for the cognitive problems that most commonly affect patients with Parkinson’s. The information gleaned from the research could help clinicians foreshadow the type of cognitive impairment a patient may experience over time, if any, and tailor treatment plans accordingly.

The Magic of Deep Brain Stimulation Surgery

Deep brain stimulation (DBS) is a neurosurgery where an electrode (or electrodes) is implanted within the deep portions of the brain with the hope of changing an abnormally functioning brain. DBS is used to treat Parkinson’s disease, essential tremor, multiple sclerosis, and even some intractable depression and obsessive-compulsive disorder. It is an exciting area of research and clinical work. Here is a video of a neurosurgeon and a neurologist talking about their work with DBS. It almost seems like magic. Like magic, it can be dangerous without proper controls. It does wonders for many people though.

 

Early Signs of Parkinson’s Disease

Parkinson’s disease is what is known as a slowly progressing neurological disorder. It usually has an onset around or after age 60 with an average of 14 years between diagnosis and death (which means that there is a slightly reduced lifespan compared to peers without Parkinson’s disease). While symptoms vary – resting tremor, gait disturbances, flattened emotions – there are some early signs that indicate that someone might have or be developing Parkinson’s disease. If you or someone you know is experiencing a number of these symptoms, contact your primary care physician. Having one or all of these symptoms does not mean you have Parkinson’s disease (I know individuals with a number of these symptoms but they do not have Parkinson’s disease) but if you are experiencing some of them and are concerned, talk with your doctor.

  1. Shaking when at rest. This usually occurs on one side of the body, often in your extremities, such as a finger or foot or a hand. The shaking might also be worse when you are tired or stressed.
  2. Reduction in sense of smell.
  3. Constipation
  4. Stooped posture where you feel like you cannot stand up straight.
  5. Changes in your walking – tripping more, difficulty picking up your feet, reduced arm swing (typically on one side).
  6. Balance problems – you feel like you are more unsteady on your feet; you might not have fallen but you feel like you might.
  7. Lightheadedness when arising from a sitting position. This is called orthostatic hypotension (drop in blood pressure that occurs when changing from a non-moving state). Again, this is only one of many potential signs; by itself it is not concerning.
  8. Changes in your handwriting, particularly if it seems sloppier, smaller, or slower.
  9. Changes in your fine finger dexterity – difficulty with small buttons, for example.
  10. Stiffness in joints or pain in parts of your body. This can seem like arthritis (and might coexist with arthritis) but is a symptom of Parkinson’s disease.
  11. Have people telling you that you do not seem as engaged in life as you used to be (i.e., emotionally). This is one way I’ve heard people talk about how the “masked face” of Parkinson’s appears. A person might appear less emotional than he used to (or even more sad).
  12. Feeling like your thinking has slowed down.
  13. Feelings of depression or just that you do not have the energy or desire to do as much as you used to do. What is often mistaken as depression is apathy, which is quite common in Parkinson’s disease. Apathy can be a sign of depression but someone can be apathetic without being depressed.

There are other signs of Parkinson’s disease but this list covers the major and some of the minor ones. Which ones are major? Loss (reduction) of sense of smell, constipation, and resting tremor are all very common in Parkinson’s disease; loss of smell and constipation often occur before tremor so they are often missed as signs of potential Parkinson’s disease. Having none, one, or all of the above symptoms does not mean you do or do not have Parkinson’s disease. Many of the symptoms above can be signs of other disorders or can be part of the ‘normal’ aging process (e.g., slightly stooped posture, slowed thinking). However, if you are experiencing some of these symptoms, please talk to your doctor, even if for nothing more than ease of mind.

Parkinson’s Disease and the Brain

The Michael J. Fox Foundation has a good, basic introduction to the neurobiology of Parkinson’s disease. The brief animate video provides an overview of affected parts of the brain as well as the role that dopamine, a neurotransmitter – a chemical in the brain that allows brain cells to communicate with each other – plays in Parkinson’s disease. Click on the link below and then click on the video link titled PARKINSON’S AND THE BRAIN to learn more about how Parkinson’s disease affects the brain.

Learn More

Can We Cure Parkinson’s Disease?

The National Parkinson’s Foundation produced a series of brief videos providing overviews of Parkinson’s disease related topics by prominent clinicians and researchers in the field of Parkinson’s disease. In one video, we are provided with an overview of the questions of whether or not we can cure Parkinson’s disease and how do we treat Parkinson’s disease.

The short answer is: no, we cannot right now cure Parkinson’s disease. We have hopes that stem cell therapies will work but there are a number of issues related to stem cells that make them potentially problematic (e.g., how do we make sure they don’t turn into cancers).

We can, however, treat symptoms of Parkinson’s disease with drug, physical, and cognitive therapies. L-dopa is effective at reducing tremors in most people and well as increasing rate and speed of movement. In some cases, deep brain stimulation is warranted. It has shown to be quite effective for many people. But for now we cannot cure Parkinson’s disease.

Common Misconceptions about Parkinson’s Disease

This brief video provides an overview of some of the common misconceptions about Parkinson’s disease, including causes, course, and outcome. For example, a single head injury will not cause Parkinson’s disease, at least there is no scientific evidence of it occurring. However, repeated head injuries might result in someone who is predisposed to Parkinson’s appear with symptoms earlier than they otherwise would be. This is the same with any environmental factors, such as pesticides or heavy metals (researchers have not shown a solid link between environmental hazards and Parkinson’s disease).

Watch this brief video for a few other misconceptions about Parkinson’s disease.

The Relationship Between Executive Function and Processing Speed

Understanding the relationship between brain (specifically subcortical structures) and cognitive processes is a field still in its infancy. The rise of structural and functional neuroimaging that started in the 1970s and really began to mature in the 1990s (with even greater changes and advancements being made today), led to the ability to measure the structure and function of various brain regions in vivo. This was and is important for neuropsychologists because it allowed them to more accurately assess the relationship between the brain and cognitive and behavioral functions.

Processing speed is a basic cognitive or brain processes that subserves many other higher-order cognitive domains. Among those higher domains is executive functioning, a somewhat broad construct that involves the organization of behaviors and behavior responses, selective attention of pertinent information and suppression of unnecessary information, and maintenance and shifting of cognitive sets. Thus, executive functioning is dependent on processing speed but processing speed is not dependent on executive functioning. If executive functioning is a car, processing speed is the engine. Having a faster or more powerful engine means that the car can go faster. More efficient engines allow the car to function at a higher level of efficiency. Thus, while processing speed and executive functions are distinct, they are related with processing speed as one of the basic cognitive processes driving executive functions.

As an example of the interaction between executive functions and processing speed in clinical applications we can look at the Stroop Color-Word task. A person who is not only able to read the words or name the colors quickly but also able to inhibit the undesired but automatic process (namely, word reading on the incongruent color-word task) will receive a higher score on the Stroop task. This would, in combination with other executive function tests, be evidence for intact or even good executive functioning.

Even on non-speeded executive tasks those with fast processing speed can benefit because they can sort through information more quickly and hopefully, efficiently – speed and efficiency are related but not exactly the same. However, not all tests of executive function rely on processing speed. A person, for example, could be slow on the Wisconsin Card Sort Test, yet not exhibit any “executive dysfunction” in that they could complete all the categories and not have an abnormal number of perseverative errors. This simply demonstrates that “executive functions” are diverse and varied.

As a basic process that is dependent on basic neuronal function and glial support, any sort of focal or diffuse injury to the brain can affect processing speed. An example of this is traumatic brain injury, which frequently results in diffuse axonal injury; this diffuse injury negatively affects cognitive processing speed. Any time the white matter is focally or grossly disrupted, processing speed is in danger of disruption itself. This disruption of white matter could be anything from axonal damage, loss of oligodendroglia (which form the myelin), or even low levels of neurotransmitters.

White matter disruption also occurs in multiple sclerosis where diffuse lesions are apparent in the white matter. This disruption also occurs more often in people with heightened vascular risk factors, such as hypertension, diabetes, and cardiovascular disease. People who have these vascular risk factors and subsequent damage to their white matter (this damage or disruption is frequently termed leukoaraiosis) have reduced processing speed and attention (Viana-Baptista et al., 2008). Lesions to subcortical structures, such as the caudate, also result in reduced processing speed (Benke et al., 2003) in addition to executive dysfunction.

In subcortical disease processes such as Huntington’s disease, which usually starts with atrophy of the caudate nuclei, or Parkinson’s disease, which starts with a loss of the majority of dopaminergic cells in the substantia nigra, processing speed is consistently affected. Some common symptoms of Parkinson’s disease are freezing and a shuffling gait; even though these symptoms are motoric, they can be indicative of the global cognitive slowing that also occurs. However, it seems that processing speed is heavily dependent on the integrity of white matter.

Because of the diffusivity of processing speed, I am not aware of any areas of the brain shown to be necessary for processing speed, outside of global white matter. As I mentioned above, damage to the caudate has been shown to affect processing speed but damage to almost any area of the brain, especially if the white matter is disrupted results in slowed processing speed. Neuropsychologists often talk about a patient who has executive dysfunction, slowed speed of processing, as well as some other cognitive deficits as exhibiting signs of a frontal-subcortical disruption – a frontal-subcortical profile. So far, no one has localized processing speed to a single area – many brain structures or areas affect it.

At this point, processing speed and executive functions cannot be “mapped” to separate basal ganglia structures or loops. Of the three classically recognized cortico-striato-thalamo-cortical loops involved in cognitive and emotional processes rather than basic motor processes, which were first introduced by Alexander, Delong, and Strick (1986), the dorsolateral prefrontal cortex circuit appears to be most correlated with processing speed (Mega & Cummings, 1994). This is also the circuit most strongly linked with executive functioning. It appears that rather than utilizing different circuits processing speed and executive functions utilize the same circuits; however, processing speed is much more globalized.

References

Alexander, G. E., DeLong, M. R., & Strick, P. L. (1986). Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Annual Review of Neuroscience, 9, 357-381.

Benke, T., Delazer, M., Bartha, L., Auer, A. (2003). Basal ganglia lesions and the theory of fronto-subcortical loops: Neuropsychological findings in two patients with left caudate lesions. Neurocase, 9, 70-85.

Mega, M. S., & Cummings, J. L. (1994). Frontal-subcortical circuits and neuropsychiatric disorders. The Journal of Neuropsychiatry and Clinical Neurosciences, 6, 358-370.

Viana-Baptista M, Bugalho P, Jordão C, Ferreira N, Ferreira A, Forjaz Secca M, Esperança-Pina JA, Ferro JM. (2008). Cognitive function correlates with frontal white matter apparent diffusion coefficients in patients with leukoaraiosis. Journal of Neurology, 255, 360-366.

PBS Frontline Explores Parkinson’s Disease

Here is the video PBS recently made about Parkinson’s disease called My Father, My Brother, and Me. From what I’ve watched so far, it’s done a good job putting a face to Parkinson’s disease while also focusing on the research and clinical aspects of it.

Symptoms of Parkinson’s Disease

Parkinson’s disease (PD) affects an estimated 1.5 million Americans and about 2% of people over 65 in the U.K. Its prevalence increases with age, although roughly 15% of Americans with Parkinson’s disease are 50 or younger. Parkinson’s disease is part of a broader spectrum of disorders known as parkinsonism. While it was viewed as fairly homogeneous in the past, researchers and clinicians now recognize the complexity of the disease and its related diseases.

The defining neurological marker of Parkinson’s disease is the destruction of the substantia nigra pars compacta, a small nucleus in the brain that is one of the major dopamine-producing brain areas. Symptoms of PD are not evident until around 80% of the neurons in the substantia nigra (literally translated as “black substance”) are destroyed. Because the substantia nigra produces dopamine, which is an important neurotransmitter, the depletion of dopamine in the brain that is associated with PD affects the striatum, which in part suppresses the subthalamic nucleus. This in turn results in more activity in the globus pallidus and substantia nigra pars reticulata, which in the end leads to more activation of the inhibitory thalamic nuclei that are involved in motor functioning. To summarize, decreased dopamine results in decreased motor activation as well as other motor problems.

The common features of Parkinson’s disease are easily remembered by the mnemonic TRAP.

  1. T – Tremor, specifically resting tremor. Tremor that occurs when moving (e.g., reaching for an object) is called essential tremor and is not a defining characteristic of PD; in fact, it is a different but related disorder.
  2. R – Rigidity. Difficulty moving and stiff arms and limbs.
  3. A – Akinesia. No or slow movements.
  4. P – Postural instability. Posture problems.

Gait abnormalities is also one of the common features of PD. It is especially useful for detecting the disease early in the process. The common gait problems are decrease height and length of step and less arm swing (i.e., walking more with a shuffle than a normal gait). People with PD also often take very small steps when turning around.

PD patients often have difficulty swallowing saliva so they often drool. They also often have micrography (very small writing) that progressively gets smaller with prolonged writing. Depression is common in PD patients as well. If given levodopa (L-dopa) they will respond. Symptoms of dementia often occur as well but they usually occur after a few years post diagnosis. However, there are often more mild cognitive changes early on in the disease process, such as slowed processing speed and slowed reaction time.

Reference

Approach to diagnosis of Parkinson disease (C. Frank, G. Pari, & J. P. Rossiter, 2006). Canadian Family Physician, 52, 862-868.