This is a very important paper out of the Mayo Clinic in Jacksonville, looking at 102 patients with autopsy-confirmed multiple system atrophy (MSA). The lead author, Dr. Koga, is the same lead author is the important “masquerading” article.
This is a paper we’ve been waiting for as it assesses the prevalence and profile of cognitive impairment in MSA. Many families in our local support group have made this paper possible through brain donation.
Here’s who was included:
“Between 1998 and 2015, 170 patients from the Mayo Clinic brain bank were given a neuropathologic diagnosis of MSA. Of those, 40 patients without any medical records or brain bank questionnaires, 16 patients with only brain bank questionnaires, and 12 patients with medical records evaluated by physicians other than neurologists were excluded from the study. The resulting cohort consisted of 102 patients having medical records with assessments by neurologists or movement disorder specialists. …. These cases were received from the following sources: CurePSP: Society for PSP | CBD and Related Disorders (n = 65), Mayo Clinic Morris K. Udall Center of Excellence for PD (n = 30), consultation cases (n = 4), Mayo Clinic Jacksonville Alzheimer’s Disease (AD) Research Center (n = 1), State of Florida AD Initiative (n = 1), and Mayo Clinic Jacksonville hospital autopsy case (n = 1).”
I estimate that Brain Support Network was responsible for half of the 65 brain donation cases with the CurePSP “brain bank” as the source. This means we are responsible for about one-third of the total brains evaluated in the study! Wow!
(The “consultation cases” might be from The Parkinson’s Institute. I’m not sure. Brain Support Network assisted in getting these brains analyzed by Mayo Jacksonville. Otherwise, the tissue would probably be sitting at The PI, never to be evaluated.)
Here’s a description of this group of 102 cases with autopsy-confirmed MSA:
“63 men and 39 women… Median age at symptom onset was 57 years, and median age at death was 65 years. Thirteen patients (13%) had a family history of dementia, and 17 (17%) had a family history of parkinsonism. Of 102 patients, 85 patients (83%) were given an antemortem diagnosis of MSA. The breakdown of the 17 misdiagnosed patients by antemortem diagnosis is as follows: progressive supranuclear palsy (PSP) in 10 (59%), [Parkinson’s Disease] PD in 4 (24%), [dementia with Lewy bodies] DLB in 1 (6%), primary progressive aphasia (PPA) in 1 (6%), and Ménière’s disease in 1 (6%). The clinical MSA phenotypes were MSA-P in 78 patients (76%) and MSA-C in 24 patients (24%). … Four patients (4%) had a concurrent pathologic diagnosis of Alzheimer’s disease. Lewy-related pathology was observed in 10 patients: 6 were brain stem type and 4 were transitional type. Seven patients (7%) had cerebrovascular pathology, and 2 patients (2%) had HpScl. Thirty-five cases (34%) were pathologically subclassified as MSA-SND, 14 cases (14%) were MSA-OPCA, 51 cases (50%) were MSA-mixed, and 2 cases (2%) could not be classified.”
What did these researchers find? “Of 102 patients, 33 (32%) were documented to have cognitive impairment. Those that received objective testing, deficits primarily in processing speed and attention/executive functions were identified, which suggests a frontal-subcortical pattern of dysfunction. Of these 33 patients with cognitive impairment, 8 patients had concurrent pathologies of dementia….although they were not given antemorten diagnoses of these diseases.”
Those concurrent pathologies of dementia included Alzheimer’s Disease, hippocampal sclerosis, and cerebrovascular pathology. (Based on my reading, none of the 8 patients had diffuse Lewy body disease, or dementia with Lewy bodies.)
Of those 33 patients, 10 were not diagnosed with MSA during life. They were diagnosed with PSP (6), PD (2), DLB (1), and PPA (1).
What is “cognitive impairment” (CI)? This includes “memory loss, forgetfulness, distractibility, word-finding difficulty, difficulty with naming, slowed thinking/bradyphrenia, and executive dysfunction.” Cognitive impairment is a step below dementia. However, 8 out of the 102 cases also had dementia that was confirmed through autopsy.
When did the cognitive impairment (CI) begin in those 33 cases? “The median duration between age of symptom onset and age at onset of CI was 2 years… Only 3 patients (9%) initially presented with CI and motor symptoms simultaneously. One patient developed CI preceding motor symptoms by 1 year.”
How do those with cognitive impairment (MSA-CI) compare to those without (MSA-NC)? “MSA-CI had an older age at onset and death than did MSA-NC… Median disease duration was 7 years in both groups. The proportion of women and the frequency of family history of dementia and parkinsonism did not differ between the 2 groups. The frequency of having a clinical diagnosis of MSA was significantly lower in MSA-CI compared with MSA-NC. … The proportion of clinical MSA phenotypes did not differ between MSA-CI and MSA-NC. Patients with MSA-CI more frequently had depression compared with those with MSA-NC, although this did not reach statistical significance.”
For many of you, the key question will be “can dementia occur in MSA?” For me, the answer is no since dementia is not caused by MSA pathology. Of course, you can have a dementing disorder along with MSA, though this is unusual (8 out of 102 cases). However, cognitive impairment can certainly occur in MSA. In this study, about one-third of those evaluated had cognitive impairment while alive. Clearly clinicians need to keep this in mind and not exclude those with cognitive impairment from an MSA diagnosis.
The full paper is available at no charge online here:
I’ve copied the abstract below.
Profile of cognitive impairment and underlying pathology in multiple system atrophy
Shunsuke Koga MD, PhD, Adam Parks PhD, Ryan J. Uitti MD, Jay A. van Gerpen MD, William P. Cheshire MD, Zbigniew K. Wszolek MD, Dennis W. Dickson MD
Movement Disorders Journal, Volume 32, Issue 3, March 2017, Pages 405–413
First published online: 15 November 2016
The objectives of this study were to elucidate any potential association between α-synuclein pathology and cognitive impairment and to determine the profile of cognitive impairment in multiple system atrophy (MSA) patients. To do this, we analyzed the clinical and pathologic features in autopsy-confirmed MSA patients.
We retrospectively reviewed medical records, including neuropsychological test data, in 102 patients with autopsy-confirmed MSA in the Mayo Clinic brain bank. The burden of glial cytoplasmic inclusions and neuronal cytoplasmic inclusions were semiquantitatively scored in the limbic regions and middle frontal gyrus. We also assessed concurrent pathologies potentially causing dementia including Alzheimer’s disease, hippocampal sclerosis, and cerebrovascular pathology.
Of 102 patients, 33 (32%) were documented to have cognitive impairment. Those that received objective testing, deficits primarily in processing speed and attention/executive functions were identified, which suggests a frontal-subcortical pattern of dysfunction. Of these 33 patients with cognitive impairment, 8 patients had concurrent pathologies of dementia. MSA patients with cognitive impairment had a greater burden of neuronal cytoplasmic inclusions in the dentate gyrus than patients without cognitive impairment, both including and excluding patients with concurrent pathologies of dementia.
The cognitive deficits observed in this study were more evident on neuropsychological assessment than with cognitive screens. Based on these findings, we recommend that clinicians consider more in-depth neuropsychological assessments if patients with MSA present with cognitive complaints. Although we did not identify the correlation between cognitive deficits and responsible neuroanatomical regions, a greater burden of neuronal cytoplasmic inclusions in the limbic regions was associated with cognitive impairment in MSA.
© 2016 International Parkinson and Movement Disorder Society