Cognitive impairment: is it due to multiple sclerosis or Alzheimer's disease?
I have always assumed that people with multiple sclerosis are protected from getting Alzheimer's disease. Why?
A week doesn’t go past without one of my patients asking me if their worsening cognition and forgetfulness are due to multiple sclerosis (MS) or if they have Alzheimer’s disease (AZD). Does this sound familiar to you?
I tell them that people with MS (pwMS) are protected from getting AZD, and their cognitive issues are likely to be due to MS and superimposed ageing, anxiety and depression, or side effects of medication or another reason, for example, poor sleep, excessive alcohol consumption, etc.
Anxiety and depression
Yes, pwMS who complain of memory problems often have anxiety and/or depression that can explain their symptoms. This can be screened for on history or simple screening questionnaires such as the Hospital Anxiety and Depression (HAD) index. You can self-administer and score yourself using the HAD scale.
Concomitant medications
Many pwMS are medications that are sedating and impair cognitive function. This includes antispastic agents, anticholinergics, gabapentinoids, opioids, antihistamines, cannabinoids and anticonvulsants. Polypharmacy is common in pwMS, and if you have cognition problems, you should see if you can come off medications that make cognition worse. In my MS practice, baclofen and centrally-acting anticholinergics are the biggest culprits. If this is new to you, please read the following newsletters:
Sleep
I have written extensively about the fact that most pwMS have a sleep disorder. Mant pwMS have obstructive sleep apnoea. If you are not getting good quality sleep, you suffer from daytime sleepiness, fatigue and cognitive problems. I include excess alcohol consumption with sleep as it disrupts your sleep. However, prolonged alcohol misuse is associated with neurotoxicity and cognitive impairment over and above its effects on sleep. Please see:
Other conditions and diseases
PwMS may develop other diseases that can be associated with cognitive problems. This includes hyper and hypothyroidism, vitamin B12 deficiency, electrolyte abnormalities, chronic renal or liver impairment, small vessel disease or multiple strokes, CNS infections (HIV, syphilis, chronic meningitis, …), etc. If your cognitive problems are new and worsening, you should have investigations to exclude these other conditions and diseases.
Ageing and Alzheirmer’s disease
Yes, MS shreds your brain and cognitive reserve and makes you more susceptible to the effects of ageing. Cognitive reserve refers to the brain's ability to adapt and function despite damage. It is influenced by factors such as education, occupation, and lifestyle. Studies have shown that individuals with higher cognitive reserve may be more resilient to cognitive decline in MS and AZD.
The patterns of cognitive decline seen in MS typically differ from those seen in AZD. These deficits affect attention, information processing speed, working memory, and executive functioning. Meanwhile, in typical AZD, memory is predominantly affected, at least initially. The type of dementia that MS causes is quite different to that seen with AZD.
Many years ago, when I was early in my MS career, I asked the head of neuropathology at Queen Square, my previous institution, how common MS and AZD were found at post-mortem. He said to me that in over 200 brain bank MS cases, he had never seen both MS and AZD. He had good data on this because the brain bank's protocol for processing tissue included staining for amyloid or AZD pathology. And the head of neuropathology was a very good pathologist. It is a pity we never wrote up this finding. However, since then, I have assumed that pwMS are protected from getting AZD.
A recent study published in the Annals of Neurology showed that pwMS have lower amyloid-β plasma positivity, a marker of AZD pathology, compared to non-MS controls (see paper below). This observation is very important as it may tell us something about the pathogenesis of AZD and could lead to new and exciting ways to prevent and treat AZD. I have lots of ideas about why MS protects you from getting AZD, but not enough time to research them.
I would be interested to hear if any of you have worsening cognition. If yes, what has your healthcare professional said about it? Have you been sent for cognitive testing? Have you had other tests done to exclude other conditions or diseases, and whether any of you have been told you have AZD?
The following are other relevant MS-Selfie newsletters relevant to this topic that you may find helpful.
Research Paper
The life expectancy of people with multiple sclerosis (MS) has increased, yet we have noted that development of a typical Alzheimer disease dementia syndrome is uncommon. We hypothesized that Alzheimer disease pathology is uncommon in MS patients. In 100 MS patients, the rate of amyloid-β plasma biomarker positivity was approximately half the rate in 300 non-MS controls matched on age, sex, apolipoprotein E proteotype, and cognitive status. Interestingly, most MS patients who did have amyloid-β pathology had features atypical for MS at diagnosis. These results support that MS is associated with reduced Alzheimer disease risk, and suggest new avenues of research. ANN NEUROL 2024;96:453-459.
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General Disclaimer
Please note that the opinions expressed here are those of Professor Giovannoni and do not necessarily reflect the positions of Queen Mary University of London or Barts Health NHS Trust. The advice is intended as general and should not be interpreted as personal clinical advice. If you have problems, please tell your healthcare professional, who will be able to help you.
Email: "Is 200 brains a large enough number to conclude that MS and Alzheimer's do not happen together?"
Yes, based on the age of the patients, I.e. the majority were over 50 with many in their 60s we would have expected ~20-30% of them to have early AZD pathology.
Ask Grok: How does the cognitive impairment associated with multiple sclerosis differ from that associated with Alzheimer's disease?
Grok's Response
Multiple Sclerosis (MS) and Alzheimer's disease both affect cognitive functions, but they do so in distinct ways due to their different pathologies:
**Multiple Sclerosis (MS):**
- **Pathology**: MS is an autoimmune disease where the immune system attacks the myelin sheath, the protective covering of nerve fibers in the brain and spinal cord. This leads to lesions or scars (sclerosis) that disrupt the transmission of nerve impulses.
- **Cognitive Impairment**:
- **Type**: MS often leads to what is known as "mild cognitive impairment" in many patients. This impairment can affect information processing speed, attention, executive functions (like planning and problem-solving), and memory, particularly short-term memory.
- **Pattern**: The cognitive deficits in MS can be inconsistent, with good days and bad days. This variability is often due to the fluctuating nature of the disease, where new lesions can temporarily or permanently affect cognitive functions.
- **Progression**: Cognitive decline in MS might not follow a predictable pattern. Some individuals might experience significant cognitive issues early on, while others might never develop noticeable cognitive impairments.
- **Emotional Impact**: MS can also lead to emotional changes, which might be mistaken for cognitive issues, like mood swings or depression, which can further impact cognitive performance.
**Alzheimer's Disease:**
- **Pathology**: Alzheimer's is characterized by the accumulation of amyloid plaques and tau protein tangles in the brain, leading to the death of neurons and loss of brain tissue over time.
- **Cognitive Impairment**:
- **Type**: Alzheimer's primarily affects memory, especially episodic memory (memory of events and experiences). As the disease progresses, it impacts other cognitive functions like language, spatial abilities, and judgment.
- **Pattern**: The progression is generally more predictable, starting with forgetfulness of recent events and gradually affecting older memories and other cognitive domains. There's a steady decline in cognitive abilities over time.
- **Progression**: Alzheimer's follows a more linear path of deterioration, with stages from mild cognitive impairment to severe dementia where individuals lose most cognitive functions.
- **Emotional and Behavioral Changes**: Alzheimer's can also lead to personality changes, delusions, and agitation, which are often more pronounced in the later stages.
**Key Differences**:
- **Nature of Impairment**: MS often leads to a patchy, inconsistent cognitive impairment where certain cognitive functions might remain relatively intact, while others fluctuate. Alzheimer's, however, typically starts with memory loss and progresses to a broad cognitive decline.
- **Pathological Basis**: MS's cognitive issues stem from demyelination and lesions, which can be widespread but are not uniformly degenerative like the neuron loss in Alzheimer's.
- **Prognosis and Progression**: MS can have periods of remission where cognitive function might improve, whereas Alzheimer's disease is relentlessly progressive with no remission.
- **Diagnosis and Management**: While both conditions can be diagnosed through a combination of clinical evaluation, imaging, and cognitive testing, the approach to management differs significantly, focusing on symptom management and disease-modifying therapies for MS, and symptomatic relief, cognitive training, and eventually palliative care for Alzheimer's.
Understanding these differences is crucial for proper diagnosis, management, and support for individuals affected by these conditions.