Lithium Treatment and Risk of Dementia

Department of Psychiatry, University Hospital of Copenhagen, Rigshospitalet, Blegdamsvej 9, DK 2100 Copenhagen, Denmark.
Archives of general psychiatry (Impact Factor: 14.48). 12/2008; 65(11):1331-5. DOI: 10.1001/archpsyc.65.11.1331
Source: PubMed


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.

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    • "Among the psychotropic drugs used in BD, the study of the effects of lithium and various anticonvulsants on cognition is of particular interest because these drugs are considered an essential pharmacological strategy due to their undeniable success as mood stabilizers. Besides the well-established clinical benefits of lithium (Wada et al., 2005; Geddes et al., 2004), recent studies have concluded that it is a neuroprotective agent and effective neurotrophic (Corbella and Vieta, 2008; Tsaltas et al., 2007; Kessing et al., 2008; Tsaltas et al., 2009; Rybakowski et al., 2009; Chi-Tso and De-Maw, 2011). However, other researchers have found that lithium can have a neurotoxic effect, even higher than that of some anticonvulsants (Gualtieri and Johnson, 2006). "
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    ABSTRACT: Background: The aim of choosing a mood-stabilizing drug (lithium or anticonvulsants) or a combination of them with minimal neurocognitive effects is to stimulate the development of criteria for a therapeutic adequacy, particularly in Bipolar Disorder (BD) patients who are clinically stabilized. Method: Three groups of BD patients were established according to their treatment: i) lithium monotherapy (n = 29); ii) lithium together with one or more anticonvulsants (n = 28); and iii) one or more anticonvulsants (n = 16). A group of healthy controls served as the control (n = 25). The following tests were applied: Wechsler Adult Intelligence Scale, Trail Making Test, Wechsler Memory Scale, Rey Complex Figure Test, Stroop color-word test, Wisconsin Card Sorting Test, Tower of Hanoi, Frontal Assessment Battery, and Reading the Mind in the Eyes Test. Results. Relative to healthy controls, BD patients showed the following: i) those on lithium monotherapy, but not other BD groups, had preserved short-term auditory memory, long-term memory, and attention; ii) those who took only anticonvulsants showed worse findings in short-term visual memory, working memory, and several executive functions; and iii) all BD patients showed worse performance in processing speed, resistance to interference, and emotion recognition. Limitations: Medication alone cannot explain why all BD patients showed common cognitive deficits despite different pharmacological treatment. Conclusion: The impairment on some executive functions and emotion recognition is an inherent trait in BD patients, regardless of their pharmacological treatment. However, while memory, attention, and most of the executive functions are preserved in long-term stable BD patients, these cognitive functions are impaired in those who take anticonvulsants.
    Journal of Affective Disorders 10/2015; DOI:10.1016/j.jad.2015.10.008 · 3.38 Impact Factor
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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). "
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    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. Copyright
    International Journal of Geriatric Psychiatry 07/2013; 28(7). DOI:10.1002/gps.3879 · 2.87 Impact Factor
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    • "Most of the evidence derives from studies of subjects with bipolar disorder. Case registry studies found a lower risk for incident dementia, in particular of AD, in bipolar patients after long-term lithium use.58,59 In a retrospective study, Terao et al found that patients on chronic lithium treatment showed lower rates of cognitive decline as measured by the Mini-Mental State Examination.60 "
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    ABSTRACT: In the last two decades, a growing body of evidence has shown that lithium has several neuroprotective effects. Several neurobiological mechanisms have been proposed to underlie these clinical effects. Evidence from preclinical studies suggests that neuroprotection induced by lithium is mainly related to its potent inhibition of the enzyme glycogen synthase kinase-3β (GSK-3β) and its downstream effects, ie, reduction of both tau protein phosphorylation and amyloid-β42 production. Additional neuroprotective effects include increased neurotrophic support, reduced proinflammatory status, and decreased oxidative stress. More recently, neuroimaging studies in humans have demonstrated that chronic use is associated with cortical thickening, higher volume of the hippocampus and amygdala, and neuronal viability in bipolar patients on lithium treatment. In line with this evidence, observational and case registry studies have shown that chronic lithium intake is associated with a reduced risk of Alzheimer's disease in subjects with bipolar disorder. Evidence from recent clinical trials in patients with mild cognitive impairment suggests that chronic lithium treatment at subtherapeutic doses can reduce cerebral spinal fluid phosphorylated tau protein. Overall, convergent lines of evidence point to the potential of lithium as an agent with disease modifying properties in Alzheimer's disease. However, additional long-term studies are necessary to confirm its efficacy and safety for these patients, particularly as chronic intake is necessary to achieve the best therapeutic results.
    Neuropsychiatric Disease and Treatment 04/2013; 9:493-500. DOI:10.2147/NDT.S33086 · 1.74 Impact Factor
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