Lithium Treatment and Risk of Dementia
ABSTRACT It has been suggested that lithium may have neuroprotective abilities, but it is not clear whether lithium reduces the risk of dementia.
To investigate whether continued treatment with lithium reduces the risk of dementia in a nationwide study.
An observational cohort study with linkage of registers of all patients prescribed lithium and diagnosed as having dementia in Denmark from January 1, 1995, through December 31, 2005.
We identified all patients treated with lithium in Denmark within community psychiatry, private specialist, and general practices and a random sample of 30% of the general population. Subjects A total of 16,238 persons who purchased lithium at least once and 1,487,177 persons from the general population who did not purchase lithium. Main Outcome Measure Diagnosis of dementia or Alzheimer disease during inpatient or outpatient hospital care.
Persons who purchased lithium at least once had an increased rate of dementia compared with persons not exposed to lithium (relative risk, 1.47; 95% confidence interval, 1.22-1.76). For persons who continued to take lithium, the rate of dementia decreased to the same level as the rate for the general population. The rate of dementia decreased early after the consumption of lithium tablets corresponding to 1 prescription (typically 100 tablets) and stayed at a low level, although with a slight increase according to the number of subsequent prescriptions. The association between the number of prescriptions for lithium and dementia was unique and different from the association between the number of prescriptions for anticonvulsants and dementia. All findings were replicated in subanalyses with Alzheimer disease as the outcome.
Continued lithium treatment was associated with reduction of the rate of dementia to the same level as that for the general population. Methodological reasons for this finding cannot be excluded, owing to the nonrandomized nature of data.
- SourceAvailable from: Liliana Dell'Osso
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- "Moreover, there is some evidence that treatments for mood disorders are associated with a reduction of dementia rate. Kessing et al. (2008, 2011) in two observational cohort studies on patients treated in psychiatric health care settings demonstrated that long-term treatment with either tricyclic antidepressants or lithium is associated with a reduced rate of dementia. Also retrospective studies carried out on AD patients suggest that a history of depression may be associated with an increased risk to develop late-onset AD (Jorm et al., 1991; Steffens et al., 1997; Green et al., 2003). "
ABSTRACT: Depression may increase the risk of developing Alzheimer's disease (AD). Recent studies have shown modifications in blood beta-amyloid (Aβ) levels in depressed patients. This literature review examines the potential relationship between Aβ-mediated neurotoxicity and pathophysiology of mood disorders. We conducted a review of the literature focusing on recent studies reporting alterations of plasma and serum Aβ peptides levels in patients suffering from mood disorders. Different data suggest that patients with mood disorders are at great risk of developing cognitive impairment and dementia. In particular, low plasma levels of Aβ42 peptide and a high Aβ40/Aβ42 ratio have been found in depressed patients. In addition, changes in Aβ protein levels in patients with mood disorders have been associated with the severity of cognitive impairment and correlated positively with the number of episodes and severity of illness course. Given the intriguing association between change in plasma level of Aβ, depression and cognitive impairment, future work should focus on the relationship between Aβ peripheral level(s), biomarkers of neurodegeneration and development of dementia in patients affected by mood disorders. CopyrightInternational Journal of Geriatric Psychiatry 07/2013; 28(7). DOI:10.1002/gps.3879 · 3.09 Impact Factor
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- "Randomized trials showed that longterm lithium treatment also improved cognitive and biological outcomes in people with amnestic mild cognitive impairment (Forlenza et al. 2011), and increased brain-derived neurotrophic factor (BDNF) serum levels in early Alzheimer's disease patients (Leyhe et al. 2009). Furthermore, in a large epidemiological study of HIV-1 infected patients, continued lithium treatment was associated with reduction of the rate of dementia to the same level as that for the general population (Kessing et al. 2008). These results suggest that treatment with lithium may prevent or delay the onset and progression of both HAND and Alzheimer's disease. "
ABSTRACT: HIV-1 transgenic (Tg) rats, a model for human HIV-1 associated neurocognitive disorder (HAND), show upregulated markers of brain arachidonic acid (AA) metabolism with neuroinflammation after 7 months of age. Since lithium decreases AA metabolism in a rat lipopolysaccharide model of neuroinflammation, and may be useful in HAND, we hypothesized that lithium would dampen upregulated brain AA metabolism in HIV-1 Tg rats. Regional brain AA incorporation coefficients k* and rates J ( in ), markers of AA signaling and metabolism, were measured in 81 brain regions using quantitative autoradiography, after intravenous [1-(14) C]AA infusion in unanesthetized 10-month-old HIV-1 Tg and age-matched wildtype rats that had been fed a control or LiCl diet for 6 weeks. k* and J ( in ) for AA were significantly higher in HIV-1 Tg than wildtype rats fed the control diet. Lithium feeding reduced plasma unesterified AA concentration in both groups and J ( in ) in wildtype rats, and blocked increments in k* (19 of 54 regions) and J ( in ) (77 of 81 regions) in HIV-1 Tg rats. These in vivo neuroimaging data indicate that lithium treatment dampened upregulated brain AA metabolism in HIV-1 Tg rats. Lithium may improve cognitive dysfunction and be neuroprotective in HIV-1 patients with HAND through a comparable effect.Journal of Neuroimmune Pharmacology 07/2012; 7(3):701-13. DOI:10.1007/s11481-012-9381-0 · 3.17 Impact Factor
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- "Foland , décrit une augmentation du volume de l'hippocampe et de l'amygdale chez des sujets bipolaires traités par lithium. Kessing , toujours à partir de données épidémiologique sur registre, conforte cliniquement la possibilité d'un effet neuroprotecteur du lithium au long cours, en mettant en évidence que le risque d'évolution démentielle des sujets bipolaires sous lithothérapie rejoignait celui des témoins. "
ABSTRACT: Le trouble bipolaire est un trouble de l’humeur fréquent qui concerne 1 à 2 % de la population. Il est sous-tendu par des mécanismes physiopathologiques multiples et revêt une présentation clinique polymorphe. Son vieillissement, encore peu étudié, est variable d’un sujet à l’autre avec une grande hétérogénéité interindividuelle. La symptomatologie des décompensations thymiques pourrait se modifier avec le temps. L’évolution démentielle observée chez certains individus semble relever de plusieurs étiologies. Il pourrait s’agir dans certaines situations d’un déclin cognitif spécifique directement en lien avec le vieillissement du trouble bipolaire, et dans d’autre cas d’une association fortuite avec une maladie neurodégénérative. Plus récemment, des liens avec la démence frontotemporale ont également été suggérés. Bipolar disorder is a common mood disorder that concerns 1–2 % of the general population. It has multiple underlying pathophysiological mechanisms and a polymorphic clinical presentation. Aging process, not sufficiently studied, varies from one subject to another and has a large inter-individual heterogeneity. Relapse symptoms may change over time. Development of dementia, which is observed in some cases, is caused by different etiological factors. In certain situations, it could be due to specific cognitive decline directly related to the aging process. In other cases, it may be due to the unfortunate association with a neurodegenerative disease. Recently, its association with frontotemporal dementia has also been suggested. Mots clésTrouble bipolaire–Démence–Démence frontotemporale–Thymorégulateur–Sujet âgé KeywordsBipolar disorder–Dementia–Frontotemporal dementia–Mood stabilizer–AgedLes cahiers de l année gérontologique 09/2011; 3(3):125-130. DOI:10.1007/s12612-011-0193-2