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Cognitive Impairment in MS (PART 2: risk factors, roles of depression and disability)
Risk Factors for Cognitive Impairment
Although there are no predictors of which patients will suffer MS-related cognitive deficits, disease duration and subtype, race, sex, and cognitive reserve may all play a role.
There are four subtypes of MS, defined by disease progression. Relapsing-remitting MS (RR-MS) is the most common; this subtype is the initial diagnosis of approximately 85 percent of all people with MS. In RR-MS, patients experience flare-ups of disease symptoms for a period of time, followed by a complete recovery or remission. The majority of patients diagnosed with RR-MS develop secondary-progressive MS (SP-MS) within 10 to 20 years. In SP-MS, as in RR-MS, patients experience flare-ups or relapses of disease symptoms, but there is a steady increase in disease severity between the relapses. The second most common subtype diagnosed at initial presentation is primary-progressive MS (PP-MS), in which a patient experiences a steady increase in symptom severity from the time of disease onset. The final and most rare subtype of MS, progressive-relapsing MS (PR-MS), involves intermittent relapses punctuating a steady progression of the disease. While patients with progressive subtypes of MS are more likely to experience cognitive impairment in general, further studies of patients with PP-MS and PR-MS are needed. Earlier onset of MS increases a patient’s chance of developing MS-related cognitive decline.
Although MS disease incidence is highest in populations from the northern United States, northern Europe, Canada, New Zealand, and southern Australia,7 people from all countries and of all races have been diagnosed with the disease. Race plays a role in disease pathogenesis and severity. For example, Caucasians have delayed symptom onset compared to Latin-American and African-American patients.8 It is possible that because clinical manifestations are more severe in African-American patients, the cognitive findings may be part of what is overall a more aggressive disease course. Race also affects MS’ impact on cognition: Adult African-American patients with MS develop cognitive deficits earlier in the disease course compared to adult Caucasian patients.9 This difference is also observed in pediatric MS patients. A 2010 study from the University of Alabama at Birmingham reported that African-American children affected by pediatric-onset MS performed worse on tests of complex attention and language compared to Caucasian children with MS matched by age, disease severity, gender, and socioeconomic status.10 A better understanding of the race-based differences in disease characteristics could help physicians tailor treatments to ensure optimal responses.
MS occurs in women more frequently than it does in men; ratios of incidence range from 2:1 to 3:1, depending on the geographical region. Despite the elevated frequency in women, studies have shown that disease severity is typically higher and progression more rapid in men compared to women. Additionally, the incidence and severity of cognitive deficits are higher in men.11
Intelligence and education history contribute to the formation of cognitive reserve, which affects the brain’s resilience in the presence of injury. Previous studies in Alzheimer’s disease (AD) have shown that individuals with higher cognitive reserve are less likely to develop dementia.12 As with AD, MS patients with high levels of cognitive reserve are less likely to experience cognitive impairment. A study following patients with MS over a five-year period showed that those with a high cognitive reserve at baseline experienced no loss of cognitive function, while those who started with a low cognitive reserve suffered a significant cognitive decline.13
The Roles of Depression and Physical Disability
Inflammation, neuronal degeneration, and lesion formation are likely among the causes of cognitive impairment in people with MS. Gray matter (neuron) loss in the brain, specifically in the cerebral cortex (the thin layer of cells that makes up the outer layer of the brain) and the thalamus (the relay station between the brain and the spinal cord, through which nearly all motor and sensory information travels), correlates with cognitive impairment.14 However, some patients with extensive brain lesions remain cognitively intact, while others with a low lesion load experience cognitive impairment. Additionally, the patterns of deficits in patients affected by cognitive impairment vary widely. For example, some patients experience relatively subtle cognitive problems, such as word-finding difficulty, while others are so debilitated that they cannot navigate roads in their own neighborhood or remember important phone numbers that used to be familiar to them. While the exact causes of cognitive impairment in MS are unknown, two factors often further impair cognitive performance in patients with the disease: depression and physical disability.
Depression often plagues people with MS-related cognitive impairment. The lifetime prevalence of depression within the general population is approximately 20 percent, while the prevalence in patients with MS is around 50 percent. A host of studies have linked depression in MS to impairments in learning, memory, processing speed, and executive function. The lesion location in an MS patient can affect depressive symptoms, as patients with brain lesions are more likely to experience depression compared to patients with spinal cord lesions. Furthermore, lesions in the temporal lobe elevate a patient’s likelihood of experiencing depression compared to lesions in other areas of the brain. Temporal lobe lesions could be the common thread linking depression and cognitive impairment, as brain structures involved in learning and memory function, such as the amygdala and the hippocampus, are located in the temporal lobes.
Depression is predominantly caused by inflammation in the brain, which is a hallmark of MS.15 Although researchers do not fully understand the pathogenesis of MS, they think inflammation precedes neuron death and myelin loss. One might hypothesize that depression would arise due to early inflammation, to be followed by degeneration of neurons and lesion development, leading to cognitive impairment.
Physical and cognitive effects of MS can occur separately, but there are relationships between them. About 10 percent of patients suffer from benign MS (that is, their score is two or below on the Expanded Disability Status Scale for at least 10 years of disease duration), in which physical disease symptoms are absent. Approximately 20 percent of patients with clinically benign MS, with a relatively mild disease course and accumulation of little disability over time, have cognitive impairment, while more than half of all MS patients suffer from cognitive impairment.
The relationships among psychological factors, fatigue, physical disability, and cognitive impairment raise some very important questions: Which of these aspects of disease arise first, and how do they interact? Does depression lead to fatigue, lowered motivation, and decreased medication compliance, thus compromising physical ability? Does physical disability or cognitive impairment make a patient more likely to become depressed and fatigued? A better understanding of disease pathogenesis and improved diagnostic tools will help researchers answer these important questions in the future.
PART 3: http://activemsers.wssnoc.net/showthread.php?t=1165
PART 1: http://activemsers.wssnoc.net/showthread.php?t=1163
PART 4: http://activemsers.wssnoc.net/showthread.php?t=1166
Although there are no predictors of which patients will suffer MS-related cognitive deficits, disease duration and subtype, race, sex, and cognitive reserve may all play a role.
There are four subtypes of MS, defined by disease progression. Relapsing-remitting MS (RR-MS) is the most common; this subtype is the initial diagnosis of approximately 85 percent of all people with MS. In RR-MS, patients experience flare-ups of disease symptoms for a period of time, followed by a complete recovery or remission. The majority of patients diagnosed with RR-MS develop secondary-progressive MS (SP-MS) within 10 to 20 years. In SP-MS, as in RR-MS, patients experience flare-ups or relapses of disease symptoms, but there is a steady increase in disease severity between the relapses. The second most common subtype diagnosed at initial presentation is primary-progressive MS (PP-MS), in which a patient experiences a steady increase in symptom severity from the time of disease onset. The final and most rare subtype of MS, progressive-relapsing MS (PR-MS), involves intermittent relapses punctuating a steady progression of the disease. While patients with progressive subtypes of MS are more likely to experience cognitive impairment in general, further studies of patients with PP-MS and PR-MS are needed. Earlier onset of MS increases a patient’s chance of developing MS-related cognitive decline.
Although MS disease incidence is highest in populations from the northern United States, northern Europe, Canada, New Zealand, and southern Australia,7 people from all countries and of all races have been diagnosed with the disease. Race plays a role in disease pathogenesis and severity. For example, Caucasians have delayed symptom onset compared to Latin-American and African-American patients.8 It is possible that because clinical manifestations are more severe in African-American patients, the cognitive findings may be part of what is overall a more aggressive disease course. Race also affects MS’ impact on cognition: Adult African-American patients with MS develop cognitive deficits earlier in the disease course compared to adult Caucasian patients.9 This difference is also observed in pediatric MS patients. A 2010 study from the University of Alabama at Birmingham reported that African-American children affected by pediatric-onset MS performed worse on tests of complex attention and language compared to Caucasian children with MS matched by age, disease severity, gender, and socioeconomic status.10 A better understanding of the race-based differences in disease characteristics could help physicians tailor treatments to ensure optimal responses.
MS occurs in women more frequently than it does in men; ratios of incidence range from 2:1 to 3:1, depending on the geographical region. Despite the elevated frequency in women, studies have shown that disease severity is typically higher and progression more rapid in men compared to women. Additionally, the incidence and severity of cognitive deficits are higher in men.11
Intelligence and education history contribute to the formation of cognitive reserve, which affects the brain’s resilience in the presence of injury. Previous studies in Alzheimer’s disease (AD) have shown that individuals with higher cognitive reserve are less likely to develop dementia.12 As with AD, MS patients with high levels of cognitive reserve are less likely to experience cognitive impairment. A study following patients with MS over a five-year period showed that those with a high cognitive reserve at baseline experienced no loss of cognitive function, while those who started with a low cognitive reserve suffered a significant cognitive decline.13
The Roles of Depression and Physical Disability
Inflammation, neuronal degeneration, and lesion formation are likely among the causes of cognitive impairment in people with MS. Gray matter (neuron) loss in the brain, specifically in the cerebral cortex (the thin layer of cells that makes up the outer layer of the brain) and the thalamus (the relay station between the brain and the spinal cord, through which nearly all motor and sensory information travels), correlates with cognitive impairment.14 However, some patients with extensive brain lesions remain cognitively intact, while others with a low lesion load experience cognitive impairment. Additionally, the patterns of deficits in patients affected by cognitive impairment vary widely. For example, some patients experience relatively subtle cognitive problems, such as word-finding difficulty, while others are so debilitated that they cannot navigate roads in their own neighborhood or remember important phone numbers that used to be familiar to them. While the exact causes of cognitive impairment in MS are unknown, two factors often further impair cognitive performance in patients with the disease: depression and physical disability.
Depression often plagues people with MS-related cognitive impairment. The lifetime prevalence of depression within the general population is approximately 20 percent, while the prevalence in patients with MS is around 50 percent. A host of studies have linked depression in MS to impairments in learning, memory, processing speed, and executive function. The lesion location in an MS patient can affect depressive symptoms, as patients with brain lesions are more likely to experience depression compared to patients with spinal cord lesions. Furthermore, lesions in the temporal lobe elevate a patient’s likelihood of experiencing depression compared to lesions in other areas of the brain. Temporal lobe lesions could be the common thread linking depression and cognitive impairment, as brain structures involved in learning and memory function, such as the amygdala and the hippocampus, are located in the temporal lobes.
Depression is predominantly caused by inflammation in the brain, which is a hallmark of MS.15 Although researchers do not fully understand the pathogenesis of MS, they think inflammation precedes neuron death and myelin loss. One might hypothesize that depression would arise due to early inflammation, to be followed by degeneration of neurons and lesion development, leading to cognitive impairment.
Physical and cognitive effects of MS can occur separately, but there are relationships between them. About 10 percent of patients suffer from benign MS (that is, their score is two or below on the Expanded Disability Status Scale for at least 10 years of disease duration), in which physical disease symptoms are absent. Approximately 20 percent of patients with clinically benign MS, with a relatively mild disease course and accumulation of little disability over time, have cognitive impairment, while more than half of all MS patients suffer from cognitive impairment.
The relationships among psychological factors, fatigue, physical disability, and cognitive impairment raise some very important questions: Which of these aspects of disease arise first, and how do they interact? Does depression lead to fatigue, lowered motivation, and decreased medication compliance, thus compromising physical ability? Does physical disability or cognitive impairment make a patient more likely to become depressed and fatigued? A better understanding of disease pathogenesis and improved diagnostic tools will help researchers answer these important questions in the future.
PART 3: http://activemsers.wssnoc.net/showthread.php?t=1165
PART 1: http://activemsers.wssnoc.net/showthread.php?t=1163
PART 4: http://activemsers.wssnoc.net/showthread.php?t=1166