Long-term Risk of Dementia in Persons With Schizophrenia

Ribe, Anette Riisgaard; Laursen, Thomas Munk; Charles, Morten; Katon, Wayne; Fenger‐Grøn, Morten; Davydow, Dimitry S.; Chwastiak, Lydia; Cerimele, Joseph M.; Vestergaard, Mogens

doi:10.1001/jamapsychiatry.2015.1546

Cited by 124 publications

(134 citation statements)

References 45 publications

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“…Similarly, the debate on whether early-life or late-life depression is more important risk factor is ongoing (3,6,(8)(9)(10)(11)(12)(13). The results of studies investigating the association between bipolar disorder and dementia (14)(15)(16)(17) and late-life schizophrenia and dementia (18)(19)(20)(21) have been equally heterogeneous.…”

Section: Introductionmentioning

confidence: 99%

Hospital-treated mental and behavioral disorders and risk of Alzheimer's disease: A nationwide nested case-control study

et al. 2017

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ArtikkelitTerveystieteiden Conflicts of Interest and Source of FundingVesa Tapiainen, Sirpa Hartikainen, Heidi Taipale and Anna-Maija Tolppanen report no competing interests. Jari Tiihonen reports serving as a consultant to AstraZeneca, Bristol-Myers Squibb, Eli Lilly, F. Hoffman-La Roche, Janssen-Cilag, Lundbeck, and Organon. He has received fees for giving expert opinions to AstraZeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen-Cilag, Lundbeck, Otsuka and Pfizer, and lecture fees from AstraZeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen-Cilag, Lundbeck, Novartis, Otsuka, and Pfizer; and grant from Stanley Foundation and Sigrid Jusélius Foundation. He is a member of advisory board in AstraZeneca, Eli Lilly, Janssen-Cilag, and Otsuka.This work was supported by European Regional Development Fund (Regional Council of Pohjois-Savo) [32198 to Vesa Tapiainen, Heidi Taipale and Anna-Maija Tolppanen]. The funder had no role in study design; in the collection, analysis, and interpretation of data, in the writing of the report; and in the decision to submit the paper for publication. Conclusions:The associations between mental and behavioral disorders and AD were modest and dependent on the time window. Therefore, some of the disorders may represent misdiagnosed prodromal symptoms of AD which underlines the importance of proper differential diagnostics among older persons. These findings also highlight the importance of appropriate time window in psychiatric and neuroepidemiology research.

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Section: Introductionmentioning

confidence: 99%

Hospital-treated mental and behavioral disorders and risk of Alzheimer's disease: A nationwide nested case-control study

et al. 2017

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“…Because of improved medical care, individuals with schizophrenia live longer and were shown to be at higher risk of late-life dementia compared to the general population (95). Therapeutic guidelines for safe treatment of elderly with chronic schizophrenia and new onset dementia represent an unmet medical need, which will become more prominent along with the demographics of aging population.…”

Section: Discussionmentioning

confidence: 99%

The Ticking of the Epigenetic Clock: Antipsychotic Drugs in Old Age

et al. 2016

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BackgroundExposed to antipsychotic drugs (APDs), older individuals with dementing illness are at risk of cerebrovascular adverse effects (CVAE), including sudden death. Transient microvascular dysfunctions are known to occur in younger persons exposed to APDs; however, they seldom progress to CVAE, suggesting that APDs alone are insufficient for engendering this untoward effect. It is, therefore, believed that a preexistent microvascular damage is necessary for CVAE to take place, but the exact nature of this lesion remains unclear. CNS small vessel disease (SVD) is a well-known age-related risk factor for strokes, dementia, and sudden death, which may constitute the initial CVAE-predisposing pathology. Therefore, we propose the two strikes CVAE paradigm, in which SVD represents the first strike, while exposure to APDs, the second. In this model, both strikes must be present for CVAE to take place, and the neuroimaging load of white matter hyperintensities may be directly proportional with the CVAE risk. To investigate this hypothesis at the molecular level, we focused on a seemingly unrelated phenomenon: both APDs and SVD were found protective against a similar repertoire of cancers and their spread to the brain (1–4). Since microRNA-29 has shown efficacy against the same malignancies and has been associated with small vessels pathology, we narrowed our search down to this miR, hypothesizing that the APDs mechanism of action includes miR-29 upregulation, which in turn facilitates the development of SVD.AimTo assess whether miR-29 can be utilized as a peripheral blood biomarker for SVD and CVAE risk.MethodWe conducted a search of experimentally verified miR-29 target genes utilizing the public domain tools miRanda, RNA22 and Weizemann Institute of Science miRNA Analysis. We identified in total 67 experimentally verified target genes for miR-29 family, 18 of which correlate with microvascular integrity and may be relevant for CVAE.ConclusionUpregulated microRNA-29 silences the expression of 18 genes connected with capillary stability, engendering a major vulnerability for SVD (first strike) which in turn increases the risk for CVAE after exposure to APDs (second strike).

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“…While people with schizophrenia are not protected against developing AD, the most common dementia in later life, it is difficult to see how AD fully explains the association between dementia and schizophrenia, for 2 reasons. First, as demonstrated by Ribe et al, 1 the typical age at onset for dementia in individuals with schizophrenia is earlier than the onset of AD. Second, the neuropathologic development of the dementia co-occurring in individuals with schizophrenia appears to be different from seen in AD.…”

Section: Only Some Individuals With Schizophrenia Develop Dementiamentioning

confidence: 92%

“…This heterogeneity, we hypothesize, is the basis for Ribe et al's observations. 1 Specifically, 1 subset of people with schizophrenia have a brain disease that develops early in life with prominent psychosis and a nonprogressive cognitive disturbance. They then develop progressive cognitive decline and dementia beginning in the fifth or sixth decade of life.…”

Section: Only Some Individuals With Schizophrenia Develop Dementiamentioning

confidence: 99%

Dementia in Patients With Schizophrenia

Peters

2015

JAMA Psychiatry

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Long-term Risk of Dementia in Persons With Schizophrenia

Cited by 124 publications

References 45 publications

Hospital-treated mental and behavioral disorders and risk of Alzheimer's disease: A nationwide nested case-control study

Hospital-treated mental and behavioral disorders and risk of Alzheimer's disease: A nationwide nested case-control study

The Ticking of the Epigenetic Clock: Antipsychotic Drugs in Old Age

Dementia in Patients With Schizophrenia

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