J Neurol Res

Journal of Neurology Research, ISSN 1923-2845 print, 1923-2853 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Neurol Res and Elmer Press Inc

Journal website https://www.neurores.org

Case Report

Volume 11, Number 3-4, August 2021, pages 60-67

Coexistence of Multiple Sclerosis and Alzheimer Disease Pathology: A Case Series

**Table 1.** Key Diagnostic Features of MS and AD
	MS	AD
MS: multiple sclerosis; AD: Alzheimer’s disease; CNS: central nervous system; DSM: Diagnostic and Statistical Manual of Mental Disorders; NIA-AA: National Institute on Aging and the Alzheimer’s Association.
Clinical diagnosis	1) McDonald criteria: dissemination of CNS lesions in time and space. 2) Rule out alternative diagnoses. 3) Diagnosis can be made clinically and/or based on MRI findings.	1) Clinical diagnosis by NIA-AA or DSM criteria: clinical signs of slowly progressive dementia. 2) Limited to “probable AD”. 3) In “probable AD”, biomarker evidence may increase diagnostic certainty.
Pathological diagnosis	1) Multiple focal regions of myelin loss in CNS termed “plaques”. 2) Diffuse tissue injury in normal appearing gray and white matter.	1) Post-mortem diagnosis required for “definite AD”. 2) Neuritic plaques and intraneuronal neurofibrillary tangles in a patient with dementia, greater in number than age-matched controls without dementia.

Table 1. Key Diagnostic Features of MS and AD

MS: multiple sclerosis; AD: Alzheimer’s disease; CNS: central nervous system; DSM: Diagnostic and Statistical Manual of Mental Disorders; NIA-AA: National Institute on Aging and the Alzheimer’s Association.

Clinical diagnosis

1) McDonald criteria: dissemination of CNS lesions in time and space.
2) Rule out alternative diagnoses.
3) Diagnosis can be made clinically and/or based on MRI findings.

1) Clinical diagnosis by NIA-AA or DSM criteria: clinical signs of slowly progressive dementia.
2) Limited to “probable AD”.
3) In “probable AD”, biomarker evidence may increase diagnostic certainty.

Pathological diagnosis

1) Multiple focal regions of myelin loss in CNS termed “plaques”.
2) Diffuse tissue injury in normal appearing gray and white matter.

1) Post-mortem diagnosis required for “definite AD”.
2) Neuritic plaques and intraneuronal neurofibrillary tangles in a patient with dementia, greater in number than age-matched controls without dementia.

**Table 2.** Summary of the Four Cases of Coexistence of MS and AD Identified in Our Search
Patient ID	Sex/race	Year birth - death (age); cause of death	MS disease course	AD disease course	MS and AD pathology
MS: multiple sclerosis; AD: Alzheimer’s disease; MRI: magnetic resonance imaging; SPMS: secondary progressive multiple sclerosis.
1	Female/Caucasian	1950 - 2010 (60 years); not determined - autopsy limited to head and spinal cord.	MRI, age 56: multiple foci of demyelination. No pre-mortem MS diagnosis (“clinical symptoms not consistent with MS”).	At age 56: cognitive impairment, decreased memory, orientation deficits. Worsening motor weakness, language deficits, rigidity and myoclonic jerks.	MS: multiple areas of demyelination consistent with MS. AD: frequent neuritic plaques and neurofibrillary tangles in the neocortex.
2	Female/Caucasian	1935 - 2013 (77 years); disseminate adenocarcinoma	SPMS Onset: at age 44, optic neuritis. Subsequent: truncal ataxia, weakness and sensory loss, disequilibrium, and urinary incontinence.	At age 59: “mental changes”, cognitive slowing, memory impairment, and impairment reading and writing.	MS: multiple demyelinated areas. AD: occasional to moderate neuritic plaques in the neocortex.
3	Female/not reported	1922 - 1997 (74 years); pneumonia and empyema	SPMS Onset: exact age unknown (between 38 and 47), diplopia. Subsequent: reduced visual acuity, fatigue, weakness and loss of sensation, unstable gait, and urinary incontinence.	At age 70: cognitive dysfunction and decreased responsiveness. Visual hallucinations, memory impairment, speech problems.	MS: multiple areas of demyelination in brain and spinal cord. AD: moderate number of neuritic plaques in the neocortex.
4	Male/not reported	1911 - 1986 (75 years); ischemic heart disease	Not reported.	Not reported.	MS: multiple demyelinated areas in brain and spinal cord. AD: neuritic plaques and neurofibrillary tangles in the neocortex.

Table 2. Summary of the Four Cases of Coexistence of MS and AD Identified in Our Search

Patient ID

Sex/race

Year birth - death (age); cause of death

MS disease course

AD disease course

MS and AD pathology

MS: multiple sclerosis; AD: Alzheimer’s disease; MRI: magnetic resonance imaging; SPMS: secondary progressive multiple sclerosis.

Female/Caucasian

1950 - 2010 (60 years); not determined - autopsy limited to head and spinal cord.

MRI, age 56: multiple foci of demyelination.
No pre-mortem MS diagnosis (“clinical symptoms not consistent with MS”).

At age 56: cognitive impairment, decreased memory, orientation deficits.
Worsening motor weakness, language deficits, rigidity and myoclonic jerks.

MS: multiple areas of demyelination consistent with MS.
AD: frequent neuritic plaques and neurofibrillary tangles in the neocortex.

Female/Caucasian

1935 - 2013 (77 years); disseminate adenocarcinoma

SPMS
Onset: at age 44, optic neuritis.
Subsequent: truncal ataxia, weakness and sensory loss, disequilibrium, and urinary incontinence.

At age 59: “mental changes”, cognitive slowing, memory impairment, and impairment reading and writing.

MS: multiple demyelinated areas.
AD: occasional to moderate neuritic plaques in the neocortex.

Female/not reported

1922 - 1997 (74 years); pneumonia and empyema

SPMS
Onset: exact age unknown (between 38 and 47), diplopia.
Subsequent: reduced visual acuity, fatigue, weakness and loss of sensation, unstable gait, and urinary incontinence.

At age 70: cognitive dysfunction and decreased responsiveness.
Visual hallucinations, memory impairment, speech problems.

MS: multiple areas of demyelination in brain and spinal cord.
AD: moderate number of neuritic plaques in the neocortex.

Male/not reported

1911 - 1986 (75 years); ischemic heart disease

Not reported.

MS: multiple demyelinated areas in brain and spinal cord.
AD: neuritic plaques and neurofibrillary tangles in the neocortex.