To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure firstname.lastname@example.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Cognitive impairment and depression are among the most prevalent and most disabling non-motor symptoms in Parkinson’s disease (PD). The genetic factors that are associated with these symptoms remain uncertain. This systematic review aims to summarise the prevailing evidence from all genetic association studies investigating the genetic variants associated with cognitive impairment and depressive symptoms in people with PD.
A systematic review using five online databases: PubMed, PsycINFO, CINAHL, EMBASE and OpenGrey (PROSPERO protocol: CRD42017067431). We completed the quality assessment using the Q-Genie tool.
2353 articles were screened, and 43 articles were found to be eligible to be included. A meta-analysis of studies investigating LRRK2 rs34637584 confirmed that the minor allele carriers had significantly less cognitive impairment (p = 0.015). Further meta-analyses showed that GBA variants rs76763715 (p < 0.001) and rs421016 (p = 0.001) were significantly associated with more cognitive impairment in people with PD. Minor alleles of GBA variants rs76763715, rs421016, rs387906315 and rs80356773 were associated with more depressive symptoms in PD. Moreover, APOE ϵ4 allele has been associated with more cognitive impairment in PD. BDNF (rs6265) and CRY1 (rs2287161) variants have been associated with more depressive symptoms in people with PD.
PD carriers of GBA variants are at high risk for cognitive decline and depression. Screening for these variants may facilitate early identification and effective management of these non-motor symptoms. The molecular mechanisms underlying favourable cognitive functioning in LRRK2 rs34637584 variant carriers warrant further investigation.
1.Available evidence confirms that the LRRK2 variant rs34637584 is associated with less cognitive impairment in people with PD.
2.GBA variants rs76763715 and rs421016 are associated with more severe cognitive impairment in people with PD.
3.The GBA variants rs76763715, rs421016, rs387906315 and rs80356773 have been significantly associated with the onset of depressive symptoms in PD.
1.This systematic review has not included studies that were not published in English. It did not include gene expression and epigenetic studies.
2.Most of the included genetic association studies were small, and they were prone to type II error.
3.There was substantial heterogeneity among the included studies.
Pharmacological interventions for Lewy body dementia (LBD), especially for its non-cognitive symptoms, are limited in their efficacy and tolerability. Clinicians are often uncertain about non-pharmacological interventions and their efficacy in managing cognitive and non-cognitive symptoms of LBD. Therefore, we aimed to systematically review the existing literature on non-pharmacological interventions for people with LBD.
We carried out a systematic search using six databases. All human studies examining impact of any non-pharmacological intervention on LBD were assessed for cognitive, physical, psychiatric, and quality-of-life outcomes. Study quality was assessed by Effective Public Health Practice Project Quality Assessment Tool for Quantitative Studies and the CARE criteria checklist.
Prevailing evidence supporting the efficacy of non-pharmacological interventions is weak. We screened 1,647 papers. Fifteen studies (n = 61) including 11 case reports were found eligible for this systematic review. Interventions and reported outcomes were heterogeneous. Deep brain stimulation of the nucleus basalis of Meynert reportedly conferred cognitive benefit. Electroconvulsive therapy and repetitive transcranial magnetic stimulation have been reported to ameliorate depressive symptoms. Transcranial direct current stimulation was observed to improve attention. Exercise-based interventions reportedly improve various clinically important outcomes. Spaced retrieval memory training and environmental intervention for “mirror sign” have also been reported.
Several non-pharmacological interventions have been studied in LBD. Although evidence supporting their efficacy is not robust, prevailing preliminary evidence and limitations of available pharmacological interventions indicate the need to consider appropriate non-pharmacological interventions, while planning comprehensive care of LBD patients. Larger trials evaluating the efficacy of non-pharmacological interventions for LBD are needed.
Despite clozapine's superior clinical efficacy in treatment-resistant schizophrenia (TRS), its adverse effects, need for periodic leukocyte monitoring, cost and variable clinical outcomes mandate a clinical need to predict its treatment response. Although cytochrome P450 1A2 (CYP1A2) is the principal determinant of metabolism of clozapine, the role of CYP1A2 gene in the clinical response to clozapine is uncertain. Hence, we investigated its association with treatment responses and adverse events of clozapine in TRS.
We evaluated four single nucleotide polymorphisms (SNP) in the CYP1A2 gene, clinical responses and serum clozapine levels in 101 consecutive patients with TRS on stable doses of clozapine. We defined clozapine response a priori and investigated allelic and genotypic associations. We assessed the socio-demographic and clinical profiles, premorbid adjustment, traumatic life events, cognition and disability of the participants, using standard assessment schedules for appropriate multivariate analyses.
Our results revealed that CYP1A2 gene SNP (*1C, *1D, *1E and *1F) were not associated with clozapine treatment response, adverse effects, serum clozapine levels or with disability (p values > 0.10).
As CYP1A2 gene SNP do not help to predict the clinical response to clozapine, routine screening for them prior to start clozapine is currently unwarranted. We suggest future longitudinal genome-wide association studies investigating clinical and pharmacogenetic variables together.
Objective: The ability to reflect rationally on one's own anomalous experiences and to recognise that their conclusions are incorrect is called as cognitive insight. It influences the delusion proneness of patients with schizophrenia. Structured instruments to assess cognitive insight have not been validated in any Indian languages so far. Hence, we aimed to evaluate the validity and factor structure of Tamil version of Beck Cognitive Insight Scale (BCIS-T).
Methods: One hundred and fifty consecutive patients with schizophrenia completed BCIS-T. We assessed their clinical insight with the reference standard, Schedule for Assessment of Insight-Expanded version (SAI-E). An independent psychiatrist evaluated their psychopathology using Brief Psychiatric Rating Scale (BPRS).
Results: BCIS-T was internally consistent with Cronbach's α 0.67 and Guttman's split-half coefficient as 0.63. BCIS-T composite index documented convergent validity with SAI-E total score (ρ = 0.38; p < 0.001) and discriminant validity with BPRS (ρ = −0.02; p = 0.85). Factor analysis showed a four-factor structure, namely self-certainty, self-reflectiveness, openness to external feedback and infallibility of self-reflection. BCIS-T composite index had significant linear relationship with clinical insight and treatment compliance on multivariate analyses (p < 0.01).
Conclusion: Our findings support the validity of BCIS-T to assess cognitive insight of the patients with schizophrenia. We suggest addressing the intricacies of cognitive insight beyond the traditional two-dimensional models in cross-cultural settings.