Psychiatric Disorders in Alzheimer Disease With the Presenilin-1 L226F Mutation

Bartesaghi, Francesca; Rosci, Chiara; Rassiga, Cecilia; Barbieri, Valentina; Gambini, Orsola; Floro, Stefano; D’Arrigo, Antonello; Sole, Angelo Del; Scarpini, Elio; Galimberti, Daniela; Priori, Alberto

doi:10.1097/wnn.0000000000000249

Cited by 6 publications

(6 citation statements)

References 18 publications

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“…As such, the actual proportion of individuals who experienced visual versus auditory hallucinations remains unclear. Nonetheless, it is notable that apart from one individual whose psychotic symptoms were not described in any detail, 23 hallucinations of some kind were reported in the vast majority of cases (41/51), while delusions were reported in nearly half of all individuals (24/51). Of those who experienced delusions, 15 had paranoia/persecutory delusions specifically and this represented the only documented psychotic symptom in 8 cases.…”

Section: Resultsmentioning

confidence: 93%

“…Thirty-three articles describing 52 individuals were included in the review, 11–43 as well as one additional study that provided limited information on another 21 individuals 44 ; however, this study is not included in the main review, as it did not report clinical and genetic information in a patient-specific manner.…”

Section: Resultsmentioning

confidence: 99%

“…15,22,23,25,29,[34][35][36] As individuals in this age range would not qualify as having "late-onset" or "very late-onset" schizophrenia, correctly diagnosing PSEN1 variant-associated dementia is likely to be difficult in such cases unless other neurological or cognitive signs/symptoms are identified. In fact, in 2 reports, it is explicitly stated that schizophrenia was mistakenly diagnosed 15,36 while in 2 others "postpartum depression with psychotic symptoms" 23 and "major depression" 29 were initially presumed. In addition, in a sequencing study not included in our review, Li et al 46 identified an L150L PSEN1 mutation in an individual diagnosed with schizophrenia; however, it is unknown if this individual also exhibited any symptoms of dementia.…”

Section: Discussionmentioning

confidence: 99%

“…Further highlighting the potential for misdiagnosis, of the 10 individuals whose age of onset was before 40 years, 8 experienced psychotic symptoms (of any kind) at or near disease onset 15,22,23,25,29,34–36 . As individuals in this age range would not qualify as having “late-onset” or “very late-onset” schizophrenia, correctly diagnosing PSEN1 variant-associated dementia is likely to be difficult in such cases unless other neurological or cognitive signs/symptoms are identified.…”

Section: Discussionmentioning

confidence: 99%

“…22,29,38 Further highlighting the potential for misdiagnosis, of the 10 individuals whose age of onset was before 40 years, 8 experienced psychotic symptoms (of any kind) at or near disease onset. 15,22,23,25,29,[34][35][36] As individuals in this age range would not qualify as having "late-onset" or "very late-onset" schizophrenia, correctly diagnosing PSEN1 variant-associated dementia is likely to be difficult in such cases unless other neurological or cognitive signs/symptoms are identified. In fact, in 2 reports, it is explicitly stated that schizophrenia was mistakenly diagnosed 15,36 while in 2 others "postpartum depression with psychotic symptoms" 23 and "major depression" 29 were initially presumed.…”

Section: Discussionmentioning

confidence: 99%

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Presenilin Gene Mutation-associated Psychosis

Colijn,

Ismail

2024

Alzheimer Disease &Amp; Associated Disorders

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Although psychotic symptoms have been described in association with rare presenilin (PSEN) gene mutations underlying early-onset Alzheimer disease (AD), no contemporary reviews on this topic exist. The purpose of this review is to characterize the psychiatric phenotype (specifically with respect to psychosis) of PSEN1 and PSEN2 variant-associated AD. A PubMed search was completed in July 2023. Only articles that described individuals harboring a PSEN1 or PSEN2 mutation who experienced symptoms of psychosis were included in the review. Thirty-three articles describing 52 individuals were included in the review, as well as one other study that provided limited information pertaining to an additional 21 cases. While visual hallucinations were the most common psychotic symptom, followed by persecutory delusions, auditory hallucinations occurred in ~17% of individuals. In ~33% of the reviewed cases psychotic symptoms were present at or near disease onset, and 9 of these individuals experienced auditory hallucinations and/or delusions in the absence of visual hallucinations (~17% of all cases). In many cases, symptoms developed at a relatively young age. As presenilin gene variant-associated psychosis may resemble a primary psychotic disorder, clinicians should be vigilant with respect to screening for signs/symptoms suggestive of neurodegeneration in first-episode psychosis.

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Section: Resultsmentioning

confidence: 93%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

Presenilin Gene Mutation-associated Psychosis

Colijn,

Ismail

2024

Alzheimer Disease &Amp; Associated Disorders

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A Novel Presenilin-1 Mutation (Leu226Val) In Early Onset Alzheimer’s Disease With Parkinsonism

Zilioli,

Misirocchi,

Pancaldi

et al. 2023

Can. J. Neurol. Sci.

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Alzheimer's disease (AD) represents the most common cause of dementia, accounting for 60% of cognitive disorders worldwide. AD is defined as early-onset (EOAD) when the clinical onset occurs before the age of 65, and it presents a higher frequency of familial clustering than the late-onset subtype.To date, variants in three causative genes such as presenilin 1 (PSEN-1), presenilin 2 (PSEN-2), and amyloid precursor protein (APP) have been identified as responsible for familial AD with Mendelian inheritance and almost complete penetrance. Overall, they account for less than 1% of all AD cases, although the prevalence peaks at about 20% in familiar EOAD. 1 PSEN-1, encoding a subunit of γ-secretase with a proteolytic activity on APP, is the main cause of monogenic AD. Thanks to the increasing availability of next-generation sequencing (NGS) panels, over 300 mutations in PSEN-1 have been discovered [https://www.alzforum.org/mutations/psen-1, accessed in March 2023), leading to a broad phenotypic variability.In 2020, a 50-years-old right-handed Caucasian man presented with a progressive and insidious onset of episodic memory deficits, reduced working ability, and neglect in his self-care.One year later, bradykinesia and left-hand action tremor appeared. Due to these symptoms, he underwent a DAT-SCAN (123I-Ioflupane) SPECT assessment, which revealed reduced uptake in the right basal ganglia. Consequently, he initiated dopaminergic treatment with L-dopa, titrated up to 200 mg/day, resulting in slight efficacy on the bradykinesia features.Two years later, the patient was admitted to our Neurology unit due to the persistence of extrapyramidal and cognitive features. His personal medical history was unremarkable and the patient did not suffer from any comorbidities. However, the assessment of his familial medical history revealed that his father had been diagnosed with cognitive impairment at about 50 years of age, and his brother had committed suicide at the age of 50.The initial clinical examination revealed a slight action tremor in the left hand, ipsilateral bradykinesia, along with plastic hypertonia and impaired visuospatial abilities. No anosmia, REM sleep behavior disorder, and dysautonomic signs were observed.

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Young-onset Alzheimer’s dementia mimicking progressive myoclonic epilepsy spectrum

Mahale,

Arunachal,

Dutta

et al. 2023

Egypt J Neurol Psychiatry Neurosurg

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Background Young-onset Alzheimer’s dementia (YOAD) refers to the onset of disease before the age of 40 years. Classical AD typically presents with memory impairment with involvement of other cognitive domains like language, visuospatial orientation. On contrary, YOAD shows phenotypic heterogeneity in the form of predominant psychiatric disturbances apart from dementia and rarely seizures, cerebellar ataxia. We report a 36-year-old lady with dementia, myoclonus, seizures and cerebellar ataxia of 3 year duration mimicking progressive myoclonic epilepsy (PME) spectrum who had novel missense mutation in PSEN1 gene (L226F) suggestive of YOAD. Case presentation A 36-year-old lady presented with seizures in the form of generalized tonic–clonic seizures of 3 year duration followed by multifocal myoclonic jerks, cognitive decline of 2 year duration and imbalance while walking of 1 year duration. Montreal cognitive assessment (MOCA) score was 6/30. Addenbrooke’s cognitive examination III (ACE-III) score was 16/100. The mental status examination showed diffuse impairment of lobar functions. Brain magnetic resonance imaging showed diffuse cerebral and cerebellar atrophy. Skin biopsy did not show Lafora bodies or dermal inclusions on electron microscopy. Whole exome sequencing showed pathogenic missense variant NM_000021.4(PSEN1):c.676C > T (p.Leu226Phe) in PSEN1 gene suggestive of YOAD. Conclusions YOAD due to PSEN1 mutation has to be considered in patients with cerebellar ataxia, seizures, myoclonus, dementia with psychiatric disturbances. This case highlights the high index of suspicion for differential diagnosis of YOAD in patients with young-onset dementia with ataxia, seizures and myoclonus.

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Psychiatric Disorders in Alzheimer Disease With the Presenilin-1 L226F Mutation

Cited by 6 publications

References 18 publications

Presenilin Gene Mutation-associated Psychosis

Presenilin Gene Mutation-associated Psychosis

A Novel Presenilin-1 Mutation (Leu226Val) In Early Onset Alzheimer’s Disease With Parkinsonism

Young-onset Alzheimer’s dementia mimicking progressive myoclonic epilepsy spectrum

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