"I Felt Like I Was Being Abused All Over Again": How Survivors of Child Sexual Abuse Make Sense of the Perinatal Period Through Their Narratives.

Sequelae following child sexual abuse pervade the lives of adult survivors, significantly impacting on pregnancy and childbirth. Symptoms of this distress are recognized, but meanings for women are less understood. This research aimed to examine the meaning for women themselves of the impact of child sexual abuse on experiences of pregnancy, childbirth, and the postnatal period. Taking a critical feminist perspective, three open-ended interviews with three survivors enabled women's narratives of pregnancy and childbirth to be heard, explored the structure of these narratives, including how experiences were connected, and identified key themes and how selves and others were positioned. Women themselves contributed to the analysis of their own narratives. The different struggles of each woman occurred within three domains of experience: identity, embodiment, and parenting. They were underpinned by a fluctuation between empowerment and disempowerment. These findings, although based on detailed analysis of the experiences of only three women, dovetail with, integrate, and extend the existent literature, offering a framework for understanding the complexity of meaning making for women. Further research might develop this. The framework may facilitate clinicians' understandings of what it is like for some women having children who have experienced child sexual abuse.

Differences in presentation and progression between severe FIC1 and BSEP deficiencies.

BACKGROUND & AIMS: Progressive familial intrahepatic cholestasis (PFIC) with normal serum levels of gamma-glutamyltranspeptidase can result from mutations in ATP8B1 (encoding familial intrahepatic cholestasis 1 [FIC1]) or ABCB11 (encoding bile salt export pump [BSEP]). We evaluated clinical and laboratory features of disease in patients diagnosed with PFIC, who carried mutations in ATP8B1 (FIC1 deficiency) or ABCB11 (BSEP deficiency). Our goal was to identify features that distinguish presentation and course of these two disorders, thus facilitating diagnosis and elucidating the differing consequences of ATP8B1 and ABCB11 mutations. METHODS: A retrospective multi-center study was conducted, using questionnaires and chart review. Available clinical and biochemical data from 145 PFIC patients with mutations in either ATP8B1 (61 "FIC1 patients") or ABCB11 (84 "BSEP patients") were evaluated. RESULTS: At presentation, serum aminotransferase and bile salt levels were higher in BSEP patients; serum alkaline phosphatase values were higher, and serum albumin values were lower, in FIC1 patients. Elevated white blood cell counts, and giant or multinucleate cells at liver biopsy, were more common in BSEP patients. BSEP patients more often had gallstones and portal hypertension. Diarrhea, pancreatic disease, rickets, pneumonia, abnormal sweat tests, hearing impairment, and poor growth were more common in FIC1 patients. Among BSEP patients, the course of disease was less rapidly progressive in patients bearing the D482G mutation. CONCLUSIONS: Severe forms of FIC1 and BSEP deficiency differed. BSEP patients manifested more severe hepatobiliary disease, while FIC1 patients showed greater evidence of extrahepatic disease.

Missense mutations and single nucleotide polymorphisms in ABCB11 impair bile salt export pump processing and function or disrupt pre-messenger RNA splicing.

UNLABELLED: The gene encoding the human bile salt export pump (BSEP), ABCB11, is mutated in several forms of intrahepatic cholestasis. Here we classified the majority (63) of known ABCB11 missense mutations and 21 single-nucleotide polymorphisms (SNPs) to determine whether they caused abnormal ABCB11 pre-messenger RNA splicing, abnormal processing of BSEP protein, or alterations in BSEP protein function. Using an in vitro minigene system to analyze splicing events, we found reduced wild-type splicing for 20 mutations/SNPs, with normal mRNA levels reduced to 5% or less in eight cases. The common ABCB11 missense mutation encoding D482G enhanced aberrant splicing, whereas the common SNP A1028A promoted exon skipping. Addition of exogenous splicing factors modulated several splicing defects. Of the mutants expressed in vitro in CHO-K1 cells, most appeared to be retained in the endoplasmic reticulum and degraded. A minority had BSEP levels similar to wild-type. The SNP variant A444 had reduced levels of protein compared with V444. Treatment with glycerol and incubation at reduced temperature overcame processing defects for several mutants, including E297G. Taurocholate transport by two assessed mutants, N490D and A570T, was reduced compared with wild-type. CONCLUSION: This work is a comprehensive analysis of 80% of ABCB11 missense mutations and single-nucleotide polymorphisms at pre-mRNA splicing and protein processing/functional levels. We show that aberrant pre-mRNA splicing occurs in a considerable number of cases, leading to reduced levels of normal mRNA. Thus, primary defects at either the protein or the mRNA level (or both) contribute significantly to BSEP deficiency. These results will help to develop mutation-specific therapies for children and adults suffering from intrahepatic cholestasis due to BSEP deficiency.

The conversational mini-mental state examination: Estimating cognitive impairment.

Formal cognitive testing is an integral part of the mental state examination, and we aimed to test whether clinicians were able to predict the score on the mini-mental state examination (MMSE) by watching a conversation between a person and the interviewer about their memory. A total of 41 professionals rated 30 patients-generally the scores on the MMSE were underestimated and experienced professionals did worse than less experienced practitioners. The results underscore the need for formal cognitive assessment and the requirements for training in the administration of cognitive tests.

Severe bile salt export pump deficiency: 82 different ABCB11 mutations in 109 families.

BACKGROUND & AIMS: Patients with severe bile salt export pump (BSEP) deficiency present as infants with progressive cholestatic liver disease. We characterized mutations of ABCB11 (encoding BSEP) in such patients and correlated genotypes with residual protein detection and risk of malignancy. METHODS: Patients with intrahepatic cholestasis suggestive of BSEP deficiency were investigated by single-strand conformation polymorphism analysis and sequencing of ABCB11. Genotypes sorted by likely phenotypic severity were correlated with data on BSEP immunohistochemistry and clinical outcome. RESULTS: Eighty-two different mutations (52 novel) were identified in 109 families (9 nonsense mutations, 10 small insertions and deletions, 15 splice-site changes, 3 whole-gene deletions, 45 missense changes). In 7 families, only a single heterozygous mutation was identified despite complete sequence analysis. Thirty-two percent of mutations occurred in >1 family, with E297G and/or D482G present in 58% of European families (52/89). On immunohistochemical analysis (88 patients), 93% had abnormal or absent BSEP staining. Expression varied most for E297G and D482G, with some BSEP detected in 45% of patients (19/42) with these mutations. Hepatocellular carcinoma or cholangiocarcinoma developed in 15% of patients (19/128). Two protein-truncating mutations conferred particular risk; 38% (8/21) of such patients developed malignancy versus 10% (11/107) with potentially less severe genotypes (relative risk, 3.7 [confidence limits, 1.7-8.1; P = .003]). CONCLUSIONS: With this study, >100 ABCB11 mutations are now identified. Immunohistochemically detectable BSEP is typically absent, or much reduced, in severe disease. BSEP deficiency confers risk of hepatobiliary malignancy. Close surveillance of BSEP-deficient patients retaining their native liver, particularly those carrying 2 null mutations, is essential.

Effect of ischemic preconditioning on the genomic response to reperfusion injury in deceased donor liver transplantation.

Ischemic preconditioning (IP) is an effective method for protecting organs from ischemia/reperfusion (IR) injury; however, the molecular basis of this protective effect is poorly understood. This study assessed the gene expression profile in liver allografts during transplantation and evaluated the impact of IP. Prereperfusion and postreperfusion biopsy specimens from livers subjected to IP (n = 19) or no preconditioning (the IR group; n = 16) were obtained. Total RNA was extracted and hybridized to GeneChip microarrays, and the findings were validated with real-time quantitative reverse-transcription polymerase chain reaction (qRT-PCR). IP livers showed less of an increase in aspartate aminotransferase after transplantation. A microarray analysis of the IR group showed increased expression of 57 genes mainly involved in cell death, inflammation and immune response, stress, and modulation of the cell cycle. The IP group showed attenuation of the expression of these genes after reperfusion. Additionally, IP led to increased expression of 43 genes involved in growth and maintenance, cell-cycle regulation, proliferation, and development. The expression of the 12 most significant genes was validated in all patients with real-time qRT-PCR, and the fold changes of a number of genes correlated with clinical parameters and graft outcomes. IP protection of liver allografts was associated with a reduction in the expression of immune response genes and promotion of those involved in protection and repair.

Carbodiimide-mediated cross-linking of RNA to nylon membranes improves the detection of siRNA, miRNA and piRNA by northern blot.

The northern blot, or RNA gel blot, is a widely used method for the discovery, validation and expression analysis of small regulatory RNA such as small interfering RNA (siRNA), microRNA (miRNA) and piwi-interacting RNA (piRNA). Although it is straightforward and quantitative, the main disadvantage of a northern blot is that it detects such RNA less sensitively than most other approaches. We found that the standard dose of UV used in northern blots was not the most efficient at immobilizing small RNA of 20-40 nt on nylon membranes. However, increasing the dose of UV reduced the detection of miRNA by hybridization in northern blotting experiments. We discovered that using the soluble carbodiimide, EDC, to cross-link RNA to nylon membranes greatly improved the detection of small RNA by hybridization. Compared to standard UV cross-linking procedures, EDC cross-linking provided a 25-50-fold increase in the sensitivity of detection of siRNA from plants and miRNA or piRNA from mammalian cells. All types of hybridization probes tested benefited from the new cross-linking procedure. Cross-linking was dependent on a terminal phosphate and so, should be applicable to other related categories of small RNA.

Outcomes of surgical management of familial intrahepatic cholestasis 1 and bile salt export protein deficiencies.

Progressive familial intrahepatic cholestasis (PFIC) with normal circulating gamma-glutamyl transpeptidase levels can result from mutations in the ATP8B1 gene (encoding familial intrahepatic cholestasis 1 [FIC1] deficiency) or the ABCB11 gene (bile salt export protein [BSEP] deficiency). We investigated the outcomes of partial external biliary diversion, ileal exclusion, and liver transplantation in these two conditions. We conducted a retrospective multicenter study of 42 patients with FIC1 deficiency (FIC1 patients) and 60 patients with BSEP deficiency (BSEP patients) who had undergone one or more surgical procedures (57 diversions, 6 exclusions, and 57 transplants). For surgeries performed prior to transplantation, BSEP patients were divided into two groups, BSEP-common (bearing common missense mutations D482G or E297G, with likely residual function) and BSEP-other. We evaluated clinical and biochemical outcomes in these patients. Overall, diversion improved biochemical parameters, pruritus, and growth, with substantial variation in individual response. BSEP-common or FIC1 patients survived longer after diversion without developing cirrhosis, being listed for or undergoing liver transplantation, or dying, compared to BSEP-other patients. Transplantation resolved cholestasis in all groups. However, FIC1 patients commonly developed hepatic steatosis, diarrhea, and/or pancreatic disease after transplant accompanied by biochemical abnormalities and often had continued poor growth. In BSEP patients with impaired growth, this generally improved after transplantation. Conclusion: Diversion can improve clinical and biochemical status in FIC1 and BSEP deficiencies, but outcomes differ depending on genetic etiology. For many patients, particularly BSEP-other, diversion is not a permanent solution and transplantation is required. Although transplantation resolves cholestasis in patients with FIC1 and BSEP deficiencies, the overall outcome remains unsatisfactory in many FIC1 patients; this is mainly due to extrahepatic manifestations. (Hepatology Communications 2018;2:515-528).

Asymptomatic spontaneous cerebral emboli predict cognitive and functional decline in dementia.

BACKGROUND: Spontaneous cerebral emboli (SCE) are frequent in Alzheimer's disease (AD) and vascular dementia (VaD). We investigated the effect of SCE on the rates of cognitive and functional decline in AD and VaD. METHODS: One hundred thirty-two patients with dementia (74 AD, National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association [NINCDS/ADRDA] criteria; 58 VaD, National Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherche et l'Enseignement en Neurosciences [NINDS/AIREN] criteria) underwent 1-hour transcranial Doppler for detection of SCE (mean [SD] age 75.5 (7.4) years; 46% female). Neuropsychological tests (Mini-Mental State Examination [MMSE], Alzheimer's Disease Assessment Scale-Cognitive subscale [ADAS-Cog], and Neuropsychiatric Inventory [NPI]) and assessment of activities of daily living (Interview for Deterioration in Daily Living Activities in Dementia [IDDD]) were performed initially and 6 months later. SCE positive (SCE+ve, n = 47) and SCE negative (SCE-ve, n = 85) patients were compared using repeated measures analyses of variance (ANOVAs) adjusted for age, gender, and cardiovascular risk factors. RESULTS: SCE+ve patients with dementia, both AD and VaD, suffered a more rapid decline in cognitive functioning over 6 months (ADAS-cog, mean increase 7.1 for SCE+ve compared with 3.3 for SCE-ve, p = .006) and activities of daily living (IDDD, mean increase 24.4 for SCE+ve compared with 10.8 for SCE-ve, p = .014). CONCLUSIONS: Asymptomatic SCE are associated with an accelerated cognitive and functional decline in dementia. SCE may be a potentially treatable cause of disease progression in dementia.

Lack of hepatocellular CD10 along bile canaliculi is physiologic in early childhood and persistent in Alagille syndrome.

Many tissues, including hepatobiliary cells, express neutral endopeptidase (CD10), encoded by MME. Serum neutral endopeptidase activity (NEA) has been recommended as a marker of cholestasis in adults but not in children with Alagille syndrome (AGS). We investigated ontogenic and disease-related differences in the expression of CD10. CD10 was found on canalicular surfaces of hepatocytes throughout the lobule in 16 adults and in 31 children aged > or =24 months, with and without cholestasis, but not in 39 children aged <24 months, with and without cholestasis. Ten AGS children aged 2 months to 6 years lacked any canalicular CD10 expression. Cholangiocyte apices and/or intrasinusoidal granulocytes marked for CD10 in all subjects. Liver membrane fractions from a child with cholestasis aged <24 months and from 2 AGS patients aged >24 months contained reduced levels of CD10. In contrast, AGS children and all controls expressed CD10 similarly on granulocytes. MME mRNA was found in the liver of children aged <24 months and of adults, all with cholestasis, and of AGS patients. Granulocyte MME mRNA levels were similar among all study subjects; however, liver MME mRNA levels were 6- to 140-fold less than in normal adults in all cholestatic subjects, including AGS children. Methylation of the MME promoter was not detected in the liver of AGS children. In conclusion, hepatocytes in early childhood physiologically lack immunohistochemically detectable CD10. Reduced MME mRNA in AGS is not due to MME promoter methylation. Liver CD10 in childhood appears to undergo reduced synthesis or rapid degradation, which persists in AGS. Absence of CD10 expression thus may limit NEA as a marker of cholestasis in young patients and in AGS.

Deletion/insertion polymorphism of the angiotensin-converting enzyme gene and white matter hyperintensities in dementia: A pilot study.

OBJECTIVES: To examine the association between the angiotensin-converting enzyme (ACE) deletion/insertion (D/I) polymorphism and white matter hyperintensities (WMHs) in patients with dementia. DESIGN: Observational pilot study with adjustment for potential confounders using analysis of covariance. SETTING: Secondary care old-age psychiatry services in greater Manchester, United Kingdom. PARTICIPANTS: Ninety-seven patients with dementia: 49 with Alzheimer's disease (AD, National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association criteria) and 48 with vascular dementia (VaD, National Institute of Neurological Disorders and Stroke/Association Internationale pour la Recherche et l'Enseignement en Neurosciences criteria). MEASUREMENTS: The ACE D/I polymorphism, WMHs (deep WMHs (DWMHs) and periventricular hyperintensities (PVHs)) on T2-weighted magnetic resonance imaging, and potential cardiovascular confounders. RESULTS: The D/D polymorphism of the ACE genotype was associated with severity of DWMH (P = .005) but not PVH (P = .34), corrected for age, cardiovascular risk factors, and type of dementia. Post hoc analyses were limited by statistical power but suggested an interaction with the apolipoprotein E epsilon4 allele. CONCLUSION: The results support previous observations that genetic factors influence the development of WMHs in dementia. The involvement of the ACE D/I polymorphism in the pathogenesis of DWMHs in dementia (AD and VaD), by a mechanism that is independent of its association with cardiovascular risk factors, should be confirmed in a large population-based sample.

Coping strategies and social support in old age psychosis.

BACKGROUND: According to vulnerability-stress models of psychosis, cognitive and behavioural coping strategies can help mediate the potentially negative effects of daily stressors. The nature, frequency and effectiveness of coping have been studied in people with psychosis under 65 years of age. However, these findings may not generalise to older people with the diagnosis, as the nature of stressors and coping strategies may change with increasing age. This study therefore aimed to explore coping in older patients with psychosis. METHODS: A total of 48 older patients with psychosis (F20-29, ICD-10) and 25 non-clinical elderly controls were compared using self-report measures of stressors, perceived control over stressors, coping strategies, perceived coping efficacy and social support. A regression analysis was used to explore predictors of dysfunctional coping in the patient group. RESULTS: Patients used a significantly higher proportion of problem-focused coping strategies, but they were more dysfunctional copers and rated their coping as less effective compared to controls. They also had fewer friends and less emotional support. Severity of symptoms was a significant predictor of dysfunctional coping when depression, cognitive impairment and functional disability were controlled. CONCLUSIONS: Patients with psychosis coped less well with daily stressors than controls and patients with more severe symptoms were more dysfunctional copers. The findings highlight the potential benefit of psychosocial interventions in old age psychosis.

The use of light therapy to lower agitation in people with dementia.

Agitation and sleep disturbance are problematic for people with dementia and their carers, and have been linked to disrupted circadian rhythms caused by a lack of exposure to light. Bright light therapy (BLT) offers a powerful and cost-effective alternative to pharmacological options, and can be easily incorporated into care routines. This article describes practical issues faced when implementing light therapy in a nursing home setting, and attempts to address existing perceptions about its effectiveness.

ATP8B1 gene expression is driven by a housekeeping-like promoter independent of bile acids and farnesoid X receptor.

BACKGROUND: Mutations in ATP8B1 gene were identified as a cause of low γ-glutamyltranspeptidase cholestasis with variable phenotype, ranging from Progressive Familial Intrahepatic Cholestasis to Benign Recurrent Intrahepatic Cholestasis. However, only the coding region of ATP8B1 has been described. The aim of this research was to explore the regulatory regions, promoter and 5'untranslated region, of the ATP8B1 gene. METHODOLOGY/PRINCIPAL FINDINGS: 5'Rapid Amplification of cDNA Ends using human liver and intestinal tissue was performed to identify the presence of 5' untranslated exons. Expression levels of ATP8B1 transcripts were determined by quantitative reverse-transcription PCR and compared with the non-variable part of ATP8B1. Three putative promoters were examined in vitro using a reporter gene assay and the main promoter was stimulated with chenodeoxycholic acid. Four novel untranslated exons located up to 71 kb upstream of the previously published exon 1 and twelve different splicing variants were found both in the liver and the intestine. Multiple transcription start sites were identified within exon -3 and the proximal promoter upstream of this transcription start site cluster was proven to be an essential regulatory element responsible for 70% of total ATP8B1 transcriptional activity. In vitro analysis demonstrated that the main promoter drives constitutive ATP8B1 gene expression independent of bile acids. CONCLUSIONS/SIGNIFICANCE: The structure of the ATP8B1 gene is complex and the previously published transcription start site is not significant. The basal expression of ATP8B1 is driven by a housekeeping-like promoter located 71 kb upstream of the first protein coding exon.

Typical investigational medicinal products follow relatively uniform regulations in 10 European Clinical Research Infrastructures Network (ECRIN) countries.

BACKGROUND: In order to facilitate multinational clinical research, regulatory requirements need to become international and harmonised. The EU introduced the Directive 2001/20/EC in 2004, regulating investigational medicinal products in Europe. METHODS: We conducted a survey in order to identify the national regulatory requirements for major categories of clinical research in ten European Clinical Research Infrastructures Network (ECRIN) countries-Austria, Denmark, France, Germany, Hungary, Ireland, Italy, Spain, Sweden, and United Kingdom-covering approximately 70% of the EU population. Here we describe the results for regulatory requirements for typical investigational medicinal products, in the ten countries. RESULTS: Our results show that the ten countries have fairly harmonised definitions of typical investigational medicinal products. Clinical trials assessing typical investigational medicinal products require authorisation from a national competent authority in each of the countries surveyed. The opinion of the competent authorities is communicated to the trial sponsor within the same timelines, i.e., no more than 60 days, in all ten countries. The authority to which the application has to be sent to in the different countries is not fully harmonised. CONCLUSION: The Directive 2001/20/EC defined the term 'investigational medicinal product' and all regulatory requirements described therein are applicable to investigational medicinal products. Our survey showed, however, that those requirements had been adopted in ten European countries, not for investigational medicinal products overall, but rather a narrower category which we term 'typical' investigational medicinal products. The result is partial EU harmonisation of requirements and a relatively navigable landscape for the sponsor regarding typical investigational medicinal products.

Bright light therapy for agitation in dementia: a randomized controlled trial.

BACKGROUND: Agitation is common in people with dementia, is distressing to patients and stressful to their carers. Drugs used to treat the condition have the potential to cause particularly severe side effects in older people with dementia and have been associated with an increased death rate. Alternatives to drug treatment for agitation should be sought. The study aimed to assess the effects of bright light therapy on agitation and sleep in people with dementia. METHODS: A single center randomized controlled trial of bright light therapy versus standard light was carried out. The study was completed prior to the mandatory registration of randomized controls on the clinical trials registry database and, owing to delays in writing up, retrospective registration was not completed. RESULTS: There was limited evidence of reduction in agitation in people on active treatment, sleep was improved and a suggestion of greater efficacy in the winter months. CONCLUSIONS: Bright light therapy is a potential alternative to drug treatment in people with dementia who are agitated.

Common definition for categories of clinical research: a prerequisite for a survey on regulatory requirements by the European Clinical Research Infrastructures Network (ECRIN).

BACKGROUND: Thorough knowledge of the regulatory requirements is a challenging prerequisite for conducting multinational clinical studies in Europe given their complexity and heterogeneity in regulation and perception across the EU member states. METHODS: In order to summarise the current situation in relation to the wide spectrum of clinical research, the European Clinical Research Infrastructures Network (ECRIN) developed a multinational survey in ten European countries. However a lack of common classification framework for major categories of clinical research was identified, and therefore reaching an agreement on a common classification was the initial step in the development of the survey. RESULTS: The ECRIN transnational working group on regulation, composed of experts in the field of clinical research from ten European countries, defined seven major categories of clinical research that seem relevant from both the regulatory and the scientific points of view, and correspond to congruent definitions in all countries: clinical trials on medicinal products; clinical trials on medical devices; other therapeutic trials (including surgery trials, transplantation trials, transfusion trials, trials with cell therapy, etc.); diagnostic studies; clinical research on nutrition; other interventional clinical research (including trials in complementary and alternative medicine, trials with collection of blood or tissue samples, physiology studies, etc.); and epidemiology studies. Our classification was essential to develop a survey focused on protocol submission to ethics committees and competent authorities, procedures for amendments, requirements for sponsor and insurance, and adverse event reporting following five main phases: drafting, consensus, data collection, validation, and finalising. CONCLUSION: The list of clinical research categories as used for the survey could serve as a contribution to the, much needed, task of harmonisation and simplification of the regulatory requirements for clinical research in Europe.

Orofacial dyskinesia, frontal lobe dysfunction, and coping in older people with psychosis.

OBJECTIVE: To investigate whether orofacial tardive dyskinesia (OTD) is associated with frontal lobe dysfunction and whether either are related to the coping abilities independent of psychiatric symptoms in older people with psychotic disorders. METHODS: A total of 52 patients, aged over 65 years or over, who satisfied International Classification of Diseases, Tenth Revision criteria for psychotic disorders (F20-F29) were recruited into the study. OTD was measured using the Abnormal Involuntary Movements Scale and Waddington et al.'s (1993) criteria. Neuropsychological measures were specifically selected to assess different aspects of frontal function and coping was measured using a semistructured interview. Psychiatric symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS). RESULTS: Patients with OTD showed more severe global cognitive impairment compared to patients without OTD. Group differences on measures of frontal lobe dysfunction were not maintained following adjustment for global cognitive impairment. Patients with OTD did not differ from patients without OTD on coping measures. Scores on the general psychopathology subscale of the PANSS, which includes symptoms associated with depression and anxiety, consistently predicted patients' negative perceptions of stressors and appraisals of coping, but cognitive impairment did not predict coping independent of symptoms. CONCLUSION: The association between coping and general psychopathology in older patients with psychosis warrants further investigation as both variables may be amenable to psychological interventions.

Cerebral emboli and depressive symptoms in dementia.

BACKGROUND: The vascular depression hypothesis and our recent findings of increased frequency of spontaneous cerebral emboli in dementia suggest that such emboli may be involved in the causation of depressive symptoms in dementia. AIMS: To evaluate the association between spontaneous cerebral emboli and depressive symptoms in Alzheimer's disease and vascular dementia. METHOD: In a cohort of 142 patients with dementia (72 with Alzheimer's disease and 70 with vascular dementia), the association between spontaneous cerebral emboli and clinically relevant depressive symptoms was examined using multiple logistic regression analyses. RESULTS: Spontaneous cerebral emboli were significantly more frequent in the patients with clinically relevant depressive symptoms (66 v. 37%, P=0.03). After adjustment for age, gender, Mini-Mental State Examination score, type of dementia and significant cardiovascular risk factors, the relationship remained significant (OR=3.47, 95% CI 1.10-10.97). CONCLUSIONS: Spontaneous cerebral emboli are associated with clinically relevant depressive symptoms in dementia, and further research is needed to explore the nature of this relationship.

Apolipoprotein E epsilon4 allele frequency in vascular dementia.

AIM: The aim of the study was to investigate whether possession of the epsilon4 allelic form of the apolipoprotein E (APOE) gene increases the risk of developing vascular dementia (VaD). METHODS: APOE allele and genotype frequencies were determined by PCR in 89 patients with possible and probable VaD and compared with those in 97 patients with possible and probable Alzheimer's disease (AD) of similar age of disease onset and ethnic background, and with 766 control subjects drawn from the same geographical region. RESULTS: The APOE epsilon4 allele frequency in all 97 patients with possible and probable AD was significantly higher (p < 0.001) than that in control subjects. However, the APOE epsilon4 allele frequency in all 89 patients with possible and probable VaD was also significantly higher (p < 0.001) than that in control subjects, but not significantly different from that in AD. The APOE epsilon4 allele frequency was similarly, and still significantly (p < 0.001), increased when only those patients with probable AD or probable VaD were considered. CONCLUSION: Possession of APOE epsilon4 allele increases the risk of VaD.