Late life bipolar disorder evolving into frontotemporal dementia mimic

Abstract

ObjectivesAlthough bipolar disorder has been understood classically as a cyclic disease with full recovery between mood episodes, in the last decade, evidence has accumulated supporting progressive features. The clinical picture of advanced or end-stage bipolar disorder is heterogeneous with possible deficits in cognition and behavior, as illustrated by our case series.CasesFrom our neuropsychiatric outpatient clinic, we describe four cases with bipolar disorder gradually developing a clinical syndrome, including apathy, disinhibition, loss of empathy, stereotypical behavior, and compulsiveness, fulfilling the criteria for possible behavioral variant frontotemporal dementia. All cases were diagnosed with bipolar 1 disorder at least 10 years before the onset of the current symptoms, which were not due to recent mood episodes or switches of medication. In all cases, 3–7 years of follow-up yielded no progression. Repeated neuroimaging was within normal limits. Cerebrospinal fluid biomarker studies were not supportive of underlying neurodegenerative pathology. C9orf72 mutation status was negative in all cases.ConclusionSymptoms fitting the criteria for possible behavioral variant frontotemporal dementia may be present in end-stage of bipolar disorder. An alternative neurodegenerative nature seems unlikely based on repeated normal neuroimaging and the absence of clinical progression. Functional involvement of the frontal-subcortical networks might play a role.

Current understandings of the trajectory and emerging correlates of cognitive impairment in bipolar disorder: An overview of evidence

“…Although not always consistent, evidence tends to indicate that older onset patients have a greater incidence of neurological comorbidities and are less likely to have a family history of psychiatric illness, suggesting that different etiological factors may be involved. Relevantly, there are case reports suggesting that early stage neurodegenerative disease can mimic psychosis and BD, such that a late manifestation of BD and associated cognitive impairment may represent a putative prodrome marker from which dementia or Alzheimer's Disease may emerge . Nonetheless, BD patients appear to be at an increased risk of developing pre‐senile and senile dementia compared to those with other psychiatric or medical conditions as well as the general population, irrespective of onset age .…”

“…Relevantly, there are case reports suggesting that early stage neurodegenerative disease can mimic psychosis and BD, such that a late manifestation of BD and associated cognitive impairment may represent a putative prodrome marker from which dementia or Alzheimer's Disease may emerge. [52][53][54] Nonetheless, BD patients appear to be at an increased risk of developing pre-senile and senile dementia compared to those with other psychiatric or medical conditions as well as the general population, irrespective of onset age. [55][56][57][58][59] A register-based study of >4200 patients with BD revealed that the long-term risk of dementia increases with the number of manic and depressive mood episodes, with a 6% increased risk for every new episode.…”

Behavioral variant frontotemporal dementia in patients with previous severe mental illness: a systematic and critical review

“…After all, their patients had cognitive performances that were regarded as only mildly impaired, had no neuroimaging abnormalities, and did not show cognitive decline during follow-up. It is noteworthy that our group retrospectively studied patients with a similar clinical history to Dols 71 , but in the findings by Gambogi et al 72 , including neuroimaging and cognitive testing, there were only subtle differences in a typical bvFTD patient. Gambogi et al found that the frequency of antipsychotic drug use, primitive reflexes, apathy, stereotypic/compulsive/ritualistic behaviors, and family history of psychosis were statistically higher in bvFTD patients with a prior history of SMI than in patients with typical bvFTD.…”

Shedding Light on Manic Syndromes and Dementia

“…The patient had a novel mutation in the progranulin (GRN) gene on chromosome 17. According to Dols [87] and colleagues, symptoms fitting the criteria for possible bvFTD may be present in the endstage of BD. Meisler and colleagues [88] reported C9ORF72 expansion (it is involved in the processes of intracellular vesicle trafficking) in a family with BD and FTD, highlighting a possible etiological relationship between the C9ORF72 expansion and disease progression from BD to FTD.…”