Psychosis in a Middle-aged Woman

PRACTICAL IMPLICATIONS

Uncommon phenotypes of autosomal dominant Alzheimer disease with unusual MRI findings may be challenging for the clinician to recognize, and thus, it is important to be aware of the potential variability of its presentation.

Presenilin-1 (PSEN1) mutations account for up to 50% of familial cases of Alzheimer disease (AD)¹ and present with a varied phenotype. The Gly206Ala variant is linked to nearly 100% penetrance,² an earlier age of symptom onset,² and is common in the Caribbean Hispanic populations. In one study, analyzing early onset AD in Florida Hispanic populations, 13 of 27 patients with PSEN-1-positive AD were reported to have the p.Gly206Ala mutation,³ a finding supported by a PSEN1 exon sequencing study which found this variant conferred the greatest risk of dementia in patients of predominantly Puerto Rican and Dominican heritage.⁴ A study comparing patients carrying the Gly206Ala mutation to sporadic patients with AD found that carriers had a lower mean age of onset (59.4), lower frequencies of the APOE ε4, but no notable difference in cognitive test scores.²

We found only one detailed case study of a p.Gly206Ala mutation carrier, which described a 59-year-old Caribbean Hispanic man with persecutory delusions and cognitive decline for 1 year before presentation after 7 years of depression and neuroleptic sensitivity.⁵ We add to the literature another case.

Case

A 55-year-old right-handed woman of a Puerto Rican descent with 9 years of education and a medical history of hypertension, dyslipidemia, and diabetes presented to our behavioral neurology clinic with a 2-year history of personality and behavior changes without a history of psychiatric disease or alcohol or drug use. Her first symptom was 100 lb weight loss from her baseline 200 lbs, for which she was diagnosed with depression. Her friend also noted other behavioral changes: she overcooked and undercooked her meals, had reduction in her home care and personal hygiene, began “fighting” in her sleep, and started compulsively eating sweets and nonfood items. More recently, she became lost in her neighborhood and started experiencing visual hallucinations, predominately of crawling bugs. At assessment, she was unable to perform basic activities of daily living and later developed dysphagia, which was felt to be a consequence of dementia. Her family history was notable for a father and paternal aunt being diagnosed with AD and a paternal cousin with schizophrenia.

Her mental status examination demonstrated redirectable lability and difficulty maintaining concentration. Mini-Mental State Examination was 10/30. No parkinsonian features were found on neurologic examination. Reversible laboratory work was unremarkable. Initial MRI of the brain without contrast demonstrated bilateral mesial temporal hyperintensities and mild nonfocal atrophy (figure 1); MRI with contrast did not show enhancement. Cerebrospinal fluid was negative for infectious, autoimmune, cytologic and paraneoplastic studies but demonstrated elevated P-tau protein and reduced Aβ₄₂/total tau index consistent with AD. Genetic testing revealed a p.Gly206Ala PSEN1 mutation. She was hospitalized 4 months later for increased paranoia and a violent assault. She was treated with trials of mood stabilizers and antipsychotics. MRI then demonstrated resolution of the bitemporal hyperintensities (figure 2). The patient was lost to follow-up.

Figure 1. Initial Brain MRI Showing Bilateral Amygdala and Anterior Hippocampus Symmetric Fluid Attenuated Inversion Recovery Hyperintense Signals.

Figure 2. Brain MRI 4 Months Later Demonstrating Resolution of Hyperintensities.

Discussion

This case describes a woman with early onset AD caused by PSEN1 Gly206Ala mutation with an atypical presentation and MRI findings that mimicked limbic encephalitis. Although few detailed phenotypic presentations of this mutation exist, there are reports of AD imitating frontotemporal dementia, similar to this patient. Presenilin mutations have been associated with alpha-synuclein in addition to AD pathology on autopsy.⁶ This may partially account for our patient's well-formed hallucinations and parasomnia and possibly the neuroleptic sensitivity in the previously described patient. Without pathology, we cannot comment further on this. Although psychosis in sporadic AD may be as high as 50%, the precise incidence in PSEN1 cases are under continued investigation.⁵ Although typical MRI findings for AD include hippocampal and temporal-parietal cortical atrophy, mild diffuse volume loss has been described,⁵ similar to our patient's imaging. Although unusual for AD, our patient's initial MRI demonstrated mesial temporal hyperintensities^1,2: a radiology study found only 7 of 65 cases with bilateral temporal hyperintensities had AD.⁷

This case highlights the importance of the clinician being aware that AD can present in younger patients with marked neuropsychiatric symptoms and atypical MRI findings. Neurodegenerative disorders should be considered even when psychiatric symptoms predominate. A thorough family history is critical in supporting a familial disposition, and genetic testing may aid the suspecting clinician when such is absent or nebulous. More detailed phenotypic descriptions of PSEN1 variants are necessary to further understand the role of the mutation in disease expression.

Appendix. Authors

Study Funding

No targeted funding reported.

Disclosure

J.G. Venditto reports no disclosures relevant to the manuscript. E. Bender reports no disclosures relevant to the manuscript. M.L. Lichtenstein reports no disclosures relevant to the manuscript. She is coinvestigator for trials funded by ADCS/Biohaven and PCORI/NIA. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/cp.