Case Report - Clinical Schizophrenia & Related Psychoses ( 2023) Volume 17, Issue 3
Late Life Psychosis with Alzheimers Biomarkers Successfully Treated with Electro Convulsive Therapy: A Case ReportJacob P. Feigal1,2* and Kim G. Johnson1,3
2Department of Medicine, Duke University School of Medicine, Durham, USA
3Department of Neurology, Duke University School of Medicine, Durham, USA
Jacob P. Feigal, Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, USA, Email: Jacob.firstname.lastname@example.org
Received: 21-Jun-2023, Manuscript No. CSRP-23-103454; Editor assigned: 23-Jun-2023, Pre QC No. CSRP-23-103454 (PQ); Reviewed: 10-Jul-2023, QC No. CSRP-23-103454; Revised: 17-Jul-2023, Manuscript No. CSRP-23-103454 (R); Published: 24-Jul-2023, DOI: 10.3371/CSRP.FJKJ.072423
Introduction: Biomarkers for Alzheimer’s Disease (AD) are available for use and are part of current clinical practice, yet little is known about the prognostic implications for psychiatric symptoms and treatment.
Case report: A 65 year old man with mild cognitive changes and normal functioning who developed psychosis and rapid functional decline. He was discovered to have Cerebro Spinal Fluid (CSF) biomarkers consistent with an AD pathologic process. He underwent Electro Convulsive Therapy (ECT) to treat worsening psychosis symptoms and demonstrated improvement in functioning back to his baseline with resolution of psychotic symptoms.
Discussion: This patient had benefit from ECT despite the presence of AD biomarkers and a severe presentation of late life psychosis. More research is needed to understand the neurobiology of late life psychosis, and the interaction between AD biomarkers and response to psychiatric treatments such as ECT .
Biomarkers • Alzheimer’s disease • Tau • Amyloid • Electroconvulsive therapy
In patients aged 65 and over, new onset psychosis is correlated with neurodegenerative diseases such as Alzheimer’s Disease and Related Dementias (ADRD) . Traditionally, Electro Convulsive Therapy (ECT) has been avoided in patients with cognitive impairment, and research on ECT in patients with dementia focuses on treating depression and agitation in advanced disease [2,3]. ECT is known to be an effective treatment for psychosis in depression, however few studies examine the effectiveness of ECT for psychosis in neurodegenerative disease. There is a lack of effective treatment options for psychosis in ADRD with no Food and Drug Administration (FDA) approved medications. We present a male patient with mild cognitive changes who developed psychosis followed by rapid functional decline and was discovered to have CSF biomarkers consistent with an AD pathologic process. He underwent ECT to treat worsening psychosis and demonstrated resolution of functional impairments and psychotic symptoms.
The patient, aged 65 with no significant psychiatric history and a family history of dementia (father and paternal grandmother), was hospitalized in a psychiatric hospital for three weeks in 1/2020 with a first episode of psychosis consisting of delusions and paranoia. Prior to the hospitalization, he was semi-retired (4 year professional degree), performed all independent Activities of Daily Living (iADL’s) and engaged in hobbies. He had mild memory changes with trouble remembering names but no formal evaluation. Delusions consisted of beliefs that he was a pawn in a scheme, someone was stealing from him and watching him and his family through the Television (TV) or phone. Patient and his wife denied current, or history of, depression symptoms. He was treated with two antipsychotic medications, quetiapine and thiothixene, but had persistent psychotic symptoms including delusions, paranoia, disorganized thought process and thought blocking.
At a follow up outpatient evaluation in 2/2020, Montreal Cognitive Assessment (MoCA) was 23/30. All labs were normal including vitamin B12, thyroid, infectious exposures, inflammatory markers, and autoimmune encephalopathy panel. Electroencephalogram (EEG) showed low normal background frequency at 8.5 Hz. Magnetic Resonance Imaging (MRI) showed mild generalized atrophy and mild small vessel white matter changes but was otherwise normal for age. CSF studies showed elevated phosphorylated-tau (p-tau) and decreased amyloid beta-42 to total-tau (t-tau) index (Athena Diagnostics), consistent with Alzheimer’s Disease pathology as shown in Table 1. Genetic testing showed APOE 3/3 (Apolipoprotein E) genotype. Provisional diagnosis of Alzheimer’s Disease was made.
|A-beta 42 to T-Tau Index (ATI)||p-tau/A-beta 42 ratio||Interpretation|
|Pre-ECT||Athena Diagnostics, ADMark||CSF||82.65(reference <54)||492.2||425.95||0.52 (reference >1.2)||n/a||Alzheimer’s Disease|
|Post-ECT||Mayo Laboratories, ADEVL||CSF||41 pg/mL
|472 (reference <238)||815
|Consistent with the presence of pathological changes associated with Alzheimer’s disease|
Note: *reference range noted where provided by the lab
Key: P-tau = Phospho-tau; T-tau = Total tau; A-beta 42 = Amyloid beta 42 peptide
Over the following 5 months, delusions and paranoia worsened, with beliefs that food and water were contaminated and that his wife was an intruder. He paced at home daily with one episode of fleeing a restaurant in public. He also developed aphasia and functional decline, needing prompting to bathe, dress and groom, as well as anorexia with a 17-pound weight loss. Consideration was given to formal neuropsychological testing, but he was not capable of participating due to psychomotor agitation. In 10/2020, ECT was recommended due to concern that agitation represented an excited catatonia. Treatment was initiated with right unilateral electrode placement and ultrabrief pulse width. After 9 treatments he had a partial response with amelioration of hyperactive behaviors, but developed staring, mutism and withdrawal.
Treatment was changed to bitemporal electrode placement with brief pulse stimulus for an additional 13 index treatments. There were no noted adverse events. By maintenance treatment number 9, tapered to an interval of 4 weeks, his cognition, functioning and behavior improved to levels prior to hospitalization in 1/2020. He had 13 total maintenance ECT treatments and concluded ECT in 11/2021. By 1/2022, he resumed all activities including overseeing complex finances, managing medications, driving distances and hobbies. Repeat MoCA in 7/2022 was 24/30; he reported persistent difficulty recalling names. Repeat CSF testing in 9/2022 redemonstrated biomarker positive Alzheimer’s Disease pathology including elevated p-tau/ abeta 42 ratio, low abeta 42, high t-tau, and high p-tau 181 (Mayo labs).
Results and Discussion
Our patient had a robust response to ECT after presenting with late-life psychotic symptoms and receiving a diagnosis of AD due to CSF biomarker results. This case provides support for careful psychiatric assessment and treatment of patients with new psychiatric symptoms, even when AD biomarkers are present. Without ECT treatment, the deterioration of this patient might have been presumed due to a rapid course of AD. Several studies show that patients with neurodegenerative disease who experience hallucinations and delusions have a more rapid course of decline and possible early death . It is possible that this patient’s symptoms were best diagnosed as a major depressive episode with psychosis, a highly ECT responsive condition, but he never endorsed depressive symptoms prior to psychosis during treatment course and so diagnostic focus remained on the psychosis and biomarker status.
Patients with normal cognition or mild cognitive impairment can experience psychosis as the initial symptom of a neurodegenerative disease . Identifying ADRD pathology as an organic cause of psychosis may be important for clinical course, prognosis and treatment. Biomarker analysis has increased the accuracy of diagnosis of ADRD, which can be identified by the A,T (N) classification system developed by the NIAAA based in the presence of β-Amyloid plaques (A), neurofibrillary Tau deposits (T) and Neurodegeneration (N) . Aβ-42 and p-tau 181 are unique to AD and measurement of their presence differentiates AD from other neurodegenerative diseases affecting cognition . More widespread biomarker analysis of patients with new onset late life psychosis will likely increase, especially as plasma biomarker measurement becomes more reliable  and new treatments become available.
Given the profound improvements seen in this case, we postulate that ECT could impact psychotic symptoms in AD through inflammatory or biochemical mechanisms. There is a known association between microglia/ macrophage activated inflammation and the development of AD pathology  and ECT treatment could decrease markers of macrophage/microglia inflammation in the CSF . Additionally, ECT increases levels of CSF Aβ-42 in depressed patients , reflecting a possible reduction in brain amyloid. It is unknown if ECT influences AD biomarker levels in patients with psychosis or cognitive disorders receiving ECT. Further study is needed to determine the safety, efficacy, and mechanisms of action of ECT for treatment resistant psychosis in individuals with AD pathology.
This case brings up several salient points about psychosis in the setting of confirmed AD pathology and its treatment, while having the limitation of lacking formal neuropsychological testing.
ECT was highly effective and without complication in this patient with late life psychosis and positive AD biomarkers reflecting AD pathology. As AD biomarkers become more widespread in clinical use, their presence should not represent a contraindication to ECT, and care is needed to ensure proper assessment and treatment of psychiatric symptoms in this population. More research is needed to understand the effects of ECT on the neuropsychiatric manifestations of neurodegenerative diseases.
Dr. Feigal and Dr. Johnson participated equally in the preparation and editing of this manuscript.
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Consent from human subjects was not necessary for this report. However, the patient was informed of the report and gave verbal consent.
Ethical publication statement
This paper has adhered to relevant ethical guidelines, and is considered to be IRB exempt given the retrospective nature.
The patient has provided consent for publication of this anonymized report.
Note: This case was included as part of a presentation for the International Society of ECT and Neurostimulation (ISEN) annual conference in 2021.
Conflict of Interest
The authors have no financial disclosures or conflict of interest.
- Liew, Tau Ming. "Neuropsychiatric Symptoms in Cognitively Normal Older Persons, and the Association with Alzheimer’s and Non-Alzheimer’s Dementia." Alzheimers Res Ther 12 (2020): 1-14.
- Oudman, Erik. "Is Electroconvulsive Therapy (ECT) Effective and Safe for Treatment of Depression in Dementia?: A Short Review." J ECT 28 (2012): 34-38.
- van den Berg, Julia F, Henk C Kruithof, Rob M Kok, and Esmee Verwijk, et al. "Electroconvulsive Therapy for Agitation and Aggression in Dementia: A Systematic Review." Am J Geriatr Psychiatry 26 (2018): 419-434.
- Wilson, Robert S, Kristin R Krueger, Julia M Kamenetsky, and Yuxiao Tang, et al. "Hallucinations and Mortality in Alzheimer Disease." Am J Geriatr Psychiatry 13 (2005): 984-990.
- Jack Jr, Clifford R, David A Bennett, Kaj Blennow, and Maria C Carrillo, et al. "NIA-AA Research Framework: Toward a Biological Definition of Alzheimer's Disease." Alzheimers Dement 14 (2018): 535-562.
- Frank, Brandon, Madeline Ally, Bailee Brekke, and Henrik Zetterberg, et al. "Plasma p-tau181 Shows Stronger Network Association to Alzheimer's Disease Dementia than Neurofilament Light and Total Tau." Alzheimers Dement 18 (2022): 1523-1536.
- Cullen, Nicholas C, Antoine Leuzy, Shorena Janelidze, and Sebastian Palmqvist, et al. "Plasma Biomarkers of Alzheimer’s Disease Improve Prediction of Cognitive Decline in Cognitively Unimpaired Elderly Populations." Nat Commun 12 (2021): 3555.
- Kinney, Jefferson W, Shane M Bemiller, Andrew S Murtishaw, and Amanda M Leisgang, et al. "Inflammation as a Central Mechanism in Alzheimer's Disease." Alzheimers Dement 4 (2018): 575-590.
- Kranaster, Laura, Carolin Hoyer, Suna S Aksay, and Jan Malte Bumb, et al. "Antidepressant Efficacy of Electroconvulsive Therapy is Associated with a Reduction of the Innate Cellular Immune Activity in the Cerebrospinal Fluid in Patients with Depression." World J Biol Psychiatry 19 (2018): 379-389.
- Kranaster, Laura, Suna Su Aksay, Jan Malte Bumb, and Christoph Janke, et al. "Electroconvulsive Therapy Selectively Enhances Amyloid β 1–42 in the Cerebrospinal Fluid of Patients with Major Depression: A Prospective Pilot Study." Eur Neuropsychopharmacol 26 (2016): 1877-1884.
Citation: Feigal , Jacob P and Kim G. Johnson. “ Late Life Psychosis with Alzheimer's Biomarkers Successfully Treated with Electro Convulsive Therapy: A Case Report.” Clin Schizophr Relat Psychoses 17 (2023). Doi: 10.3371/CSRP.FJKJ.072423.
Copyright: � 2023 Feigal JP, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.