A case series on the hypothesized connection between dementia and bipolar spectrum disorders: bipolar type VI?

J Affect Disord. 2008 Apr;107(1-3):307-15. doi: 10.1016/j.jad.2007.08.018. Epub 2007 Sep 21.


Background: The concept of bipolar spectrum disorders has opened therapeutic opportunities for patients with atypical and complex affective conditions. The literature has recently described several commonalities in pathophysiological processes of bipolar disorders and dementia. However, this connection has been insufficiently appreciated at the clinical level, in part because affective dysregulation in the elderly and, particularly in the dementia setting, is typically attributed either to secondary depressive states or otherwise relegated to a neurologically understandable behavioral complication resulting from cerebral disease.

Methods: We selected a case series of 10 elderly patients with late-onset mood and related behavioral symptomatology and cognitive decline without past history of clear-cut bipolar disorder. Clinical features, temperament, cognition, family history and pharmacological response were assessed to identify prototypical patients to illustrate the complexities of the dementia-bipolar interface.

Results: Mixed and depressive mood symptoms were most commonly observed and all patients had been premorbidly of hyperthymic, cyclothymic and/or irritable temperaments. Most patients had a family history of bipolar disorder or disorders related to the bipolar diathesis. Symptoms were often refractory to or aggravated by antidepressants and acetylcholinesterase inhibitors, whereas mood stabilizers and/or atypical antipsychotics were beneficial, promoting behavioral improvement in all treated patients and marked cognitive recovery in five.

Limitations: Case series with retrospective methodology.

Conclusion and clinical implications: Patients with cognitive decline and frequent mood lability might be manifesting a late-onset bipolar spectrum disorder, which we posit as type VI. We further posit that dementia and/or other biopsychosocial challenges associated with aging might release latent bipolarity in such individuals. Antidepressants, even drugs targeting dementia, might aggravate the behavioral dysregulation in these patients. Evaluation of premorbid temperament and/or family history of bipolarity and related disorders might help in broadening the clinical and biological understanding of such patients, providing a rationale for better customized treatment along the lines of mood stabilization and avoidance of antidepressants.

Publication types

  • Case Reports
  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Age of Onset
  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / diagnosis
  • Alzheimer Disease / psychology
  • Anticonvulsants / therapeutic use
  • Antidepressive Agents / adverse effects
  • Antidepressive Agents / therapeutic use
  • Antipsychotic Agents / therapeutic use
  • Bipolar Disorder / diagnosis*
  • Bipolar Disorder / drug therapy
  • Bipolar Disorder / psychology
  • Cognition Disorders / diagnosis*
  • Cognition Disorders / drug therapy
  • Cognition Disorders / psychology
  • Dementia / diagnosis*
  • Dementia / drug therapy
  • Dementia / psychology
  • Diagnosis, Differential
  • Female
  • Humans
  • Lithium Compounds / therapeutic use
  • Male
  • Middle Aged
  • Models, Psychological
  • Mood Disorders / diagnosis
  • Mood Disorders / psychology
  • Temperament / classification


  • Anticonvulsants
  • Antidepressive Agents
  • Antipsychotic Agents
  • Lithium Compounds