Disease-specific Effects Research Articles

Condition-Specific Preference-Based Measures: Benefit or Burden?

ObjectivesSome argue that generic preference-based measures (PBMs) are not sensitive to certain disease-specific improvements. To overcome this problem, new condition-specific PBMs (CS-PBMs) are being developed, but it is not yet clear how such measures compare with existing generic PBMs. MethodWe generated CS-PBMs from three condition-specific questionnaires (Health Assessment Questionnaire for arthritis, Quality of Life Questionnaire for Cancer 30 for cancer, and Multiple Sclerosis Impact Scale 29 for multiple sclerosis). First, the questionnaires were reduced in content, and then, a time trade-off study was conducted in the general public (N = 402) to obtain weights associated with the dimensions and levels of the new questionnaire. Finally, we compared utilities obtained by using the CS-PBMs with utilities obtained by using the EuroQol five-dimensional (EQ-5D) questionnaire in four data sets. ResultsUtility values generated by the CS-PBMs were higher than those of the EQ-5D questionnaire. The Health Assessment Questionnaire–based measure for arthritis proved to be insensitive to comorbidities. Measures based on the Multiple Sclerosis Impact Scale 29 and the Quality of Life Questionnaire for Cancer 30 discriminated comorbidities and side effect equally well as the EQ-5D questionnaire and were more sensitive than the EQ-5D questionnaire for mild impairments. ConclusionsThe introduction of PBMs that are specific to a certain disease may have the merit of sensitivity to disease-specific effects of interventions. That gain, however, is traded off to the loss of comparability of utility values and, in some cases, insensitivity to side effects and comorbidity. The use of a CS-PBM for cost-utility analysis is warranted only under strict conditions.

Down-Regulation of Shadoo in Prion Infections Traces a Pre-Clinical Event Inversely Related to PrPSc Accumulation

During prion infections of the central nervous system (CNS) the cellular prion protein, PrPC, is templated to a conformationally distinct form, PrPSc. Recent studies have demonstrated that the Sprn gene encodes a GPI-linked glycoprotein Shadoo (Sho), which localizes to a similar membrane environment as PrPC and is reduced in the brains of rodents with terminal prion disease. Here, analyses of prion-infected mice revealed that down-regulation of Sho protein was not related to Sprn mRNA abundance at any stage in prion infection. Down-regulation was robust upon propagation of a variety of prion strains in Prnp a and Prnp b mice, with the exception of the mouse-adapted BSE strain 301 V. In addition, Sho encoded by a TgSprn transgene was down-regulated to the same extent as endogenous Sho. Reduced Sho levels were not seen in a tauopathy, in chemically induced spongiform degeneration or in transgenic mice expressing the extracellular ADan amyloid peptide of familial Danish dementia. Insofar as prion-infected Prnp hemizygous mice exhibited accumulation of PrPSc and down-regulation of Sho hundreds of days prior to onset of neurologic symptoms, Sho depletion can be excluded as an important trigger for clinical disease or as a simple consequence of neuronal damage. These studies instead define a disease-specific effect, and we hypothesize that membrane-associated Sho comprises a bystander substrate for processes degrading PrPSc. Thus, while protease-resistant PrP detected by in vitro digestion allows post mortem diagnosis, decreased levels of endogenous Sho may trace an early response to PrPSc accumulation that operates in the CNS in vivo. This cellular response may offer new insights into the homeostatic mechanisms involved in detection and clearance of the misfolded proteins that drive prion disease pathogenesis.

How might physical activity benefit patients with Parkinson disease?

Parkinson disease (PD) is a neurodegenerative disorder characterized by progressive motor and nonmotor impairments. These impairments incline many patients towards a sedentary lifestyle, which has many deleterious consequences. Accumulating evidence suggests that patients with PD might benefit from physical activity and exercise in a number of ways, from general improvements in health to disease-specific effects and, potentially, disease-modifying effects (suggested by animal data). Many issues remain to be addressed, including the need to perform clinical trials to demonstrate these presumed benefits of physical activity and exercise in patients with PD. These trials must also address safety issues, such as an increased risk of falls and cardiovascular complications in more-active patients. Identifying ways to induce a sustained behavioral change, using specifically tailored programs that address potential barriers such as depression, apathy and postural instability, may lead to an improved quality of life in individuals with PD.

Long term antipsychotic treatment does not alter metabolite concentrations in rat striatum: An in vivo magnetic resonance spectroscopy study

Proton magnetic resonance spectroscopy (MRS) studies of schizophrenic patients generally reveal reduced levels of N-acetyl aspartate (NAA) when compared with healthy controls. Whether this reduction is due to the disease or to the drugs used for treatment remains an open question. Numerous human and animal studies have attempted to determine the effects of antipsychotics on NAA levels with mixed results. The majority of the animal studies were ex vivo, which may not accurately reflect the in vivo situation, and limitations of the human studies include previous or concomitant medications or other confounds. To overcome these limitations, we dosed 10 rats/group for six months via drinking water with 0.2 or 2 mg/kg/day haloperidol or 10 or 30 mg/kg/day clozapine. Control rats received unadulterated water. Proton MRS data were collected longitudinally over the six month period from a 64 μL voxel containing primarily the right striatum prior to and monthly during drug administration and used to estimate the concentrations of NAA, creatine, and choline. Ratios of NAA, choline, inositol and glutamate + glutamine to creatine were also calculated. Only the Cho/Cr ratio showed a significant time-by-treatment effect (p = 0.0285). These results are in agreement with previous studies of the striatum. However, regional and disease-specific effects remain unresolved.

Genome-wide association with MRI atrophy measures as a quantitative trait locus for Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder with considerable evidence suggesting an initiation of disease in the entorhinal cortex and hippocampus and spreading thereafter to the rest of the brain. In this study, we combine genetics and imaging data obtained from the Alzheimer's Disease Neuroimaging Initiative and the AddNeuroMed study. To identify genetic susceptibility loci for AD, we conducted a genome-wide study of atrophy in regions associated with neurodegeneration in this condition. We identified one single-nucleotide polymorphism (SNP) with a disease-specific effect associated with entorhinal cortical volume in an intron of the ZNF292 gene (rs1925690; P-value=2.6 × 10(-8); corrected P-value for equivalent number of independent quantitative traits=7.7 × 10(-8)) and an intergenic SNP, flanking the ARPP-21 gene, with an overall effect on entorhinal cortical thickness (rs11129640; P-value=5.6 × 10(-8); corrected P-value=1.7 × 10(-7)). Gene-wide scoring also highlighted PICALM as the most significant gene associated with entorhinal cortical thickness (P-value=6.7 × 10(-6)).

Disease-Specific Moral Hazard and Optimal Health Insurance Design for Physician Services

ABSTRACT This article analyzes disease-specific moral hazard effects in the demand for physician office visits and explores whether optimal insurance for physician services should be designed to have disease-specific cost sharing. Generalized method of moments is implemented to address the endogeneity of private health insurance, and the nonnegativity and the discreteness of physician services use. The results indicate that the moral hazard effect varies considerably across disease-specific specialist care. The strongest moral hazard (for no-condition related specialist visits) is almost twice the moral hazard effect of the weakest (for chronic condition related specialist visits). Although the findings indicate some variation in the moral hazard effect across disease-specific general practitioner visits, the variation is less considerable. The main policy implication is that optimal insurance for physician services should be designed to have differential cost sharing based on disease status rather than to have uniform cost sharing. (ProQuest: ... denotes formulae omitted.) INTRODUCTION Private health insurance policies provide for a price reduction at the time the insured purchases medical care. Consequently, an insured individual would respond to the price decrease by purchasing more medical care than he would have purchased at the market price, ceteris paribus. This effect of insurance on medical care demand is known as the ex post moral hazard effect (Arrow, 1963; Pauly, 1968).1 It refers to the effect of insurance on the net price of medical care and to the consequent incentive effects on medical care consumption.2 This article analyzes disease-specific moral hazard effects (i.e., the effect of health insurance on the demand for medical care associated with similar disease states) in the demand for physician office visits. The article disaggregates speciahst and general practitioner visits into three disease-specific components and seeks to identify whether there is any variation in the magnitude of moral hazard across them. The outcome has implications for optimal health insurance design, in particular, whether health insurance for physician services should be designed to have differential cost sharing that depends on the respective demand characteristics of individual diseasespecific service categories. One contribution of this article is to the recent literature that analyzes disease-specific moral hazard effects.3 An individual's preferences toward physician care may vary by disease state, which suggests that physician services associated with different diseases may have different marginal benefit configurations; therefore, the price responsiveness of the individual-consumer physician care demand may vary by disease state. Consequently, the moral hazard effect may vary across physician services associated with different disease states, since if the individual-consumer demand for a physician service is less (highly) elastic, the extent of moral hazard would be lower (higher). Disease-specific physician services variables are constructed using the three-digit ICD-9-CM disease classification codes.4 Employing data from the Medical Expenditure Panel Survey, each specialist and general practitioner service category is classified in three groups: services associated with chronic conditions, services associated with acute conditions, and services that are not associated with any medical conditions. Another contribution of this article is to the health insurance design literature that emphasizes the state specificity of optimal insurance policies. The conventional theory of the demand for health insurance, which suggests that individuals buy insurance to achieve certainty with regard to the consumption of other goods, motivates diseasespecific cost sharing. According to this theory, although the risk avoidance aspect of insurance benefits consumers, it also creates a welfare loss, since the moral hazard consumption involves consumption of medical services whose value to the consumer is less than its cost of production (Pauly, 1968; Feldstein, 1973; Feldman and Dowd, 1991; Marining and Marquis, 1996). …

Reporting of Disease-specific Treatment Effects in Randomized Controlled Trials: Systematic Review and Analysis of the Medical Literature

Reporting of Disease-specific Treatment Effects in Randomized Controlled Trials: Systematic Review and Analysis of the Medical Literature

COMT Val158Met polymorphism in relation to activation and de-activation in the prefrontal cortex: A study in patients with schizophrenia and healthy subjects

The Val158Met polymorphism in the COMT gene has been found to be associated with differences in brain activation in both healthy subjects and patients with schizophrenia. The predominant finding has been increased prefrontal activation associated with the Val allele; however, genotype-related de-activations have not been studied. In this study 42 schizophrenia patients and 31 controls underwent fMRI while performing the n-back task. Brain differences related to presence/absence of disease and presence/absence of the Val/Val genotype were examined. Both disease and Val/Val genotype were associated with failure of de-activation in a cluster centred in the medial prefrontal cortex. There was no interaction between disease and genotype at this location, but clusters where there were significant interactions emerged in the right prefrontal cortex and left temporal/parietal cortex. These findings suggest that Val158Met polymorphism influences task-related de-activations in the default mode network in both healthy subjects and schizophrenia patients to an equivalent extent. However the Val158Met polymorphism also has disease-specific effects on DLPFC activation in schizophrenia.

Inhibitors of Deacetylases Suppress Oncogenic KIT Signaling, Acetylate HSP90, and Induce Apoptosis in Gastrointestinal Stromal Tumors

Gastrointestinal stromal tumors (GIST) are characterized by activating mutations of KIT or platelet-derived growth factor receptor A (PDGFRA), and treatment with the tyrosine kinase inhibitor imatinib yields responses in the majority of patients. However, most patients develop secondary resistance, which is associated with a dismal prognosis. Histone deacetylase inhibitors (HDACI) have been shown to enhance imatinib activity in imatinib-resistant chronic myelogenous leukemia. Against this background, we explored whether HDACI might provide an alternative therapeutic strategy to KIT/PDGFRA kinase inhibitors in GIST. Inhibition of cell proliferation by HDACI was seen in KIT-positive but not in KIT-negative GIST cell lines, suggesting that HDACI activity is mainly conferred by targeting oncogenic KIT. KIT activity, expression, and activation of downstream pathways were strongly inhibited by several HDACI (SAHA, LBH589, VPA, trichostatin A, and NaButyrate). SAHA and LBH589 induced apoptosis in KIT-positive GIST, and strong synergism with imatinib was observed at low concentrations of SAHA and LBH589. Mechanistically, treatment with HDACI reduced KIT mRNA transcript levels and led to strong acetylation of HSP90, interfering with its activity as KIT chaperone. These results provide preclinical evidence for a disease-specific effect of HDACI in KIT-positive GIST, which could translate into therapeutic activity.

Apolipoprotein E ε4 is associated with disease-specific effects on brain atrophy in Alzheimer's disease and frontotemporal dementia

Apolipoprotein epsilon4 (apoE4) has been strongly linked with Alzheimer's disease (AD) and contributes to several other neurological disorders. We investigated the influence of epsilon4 allele carrier status on the pattern of gray matter atrophy and disease severity in 51 patients with probable AD and 31 patients with behavioral variant frontotemporal dementia (bvFTD), compared with 56 healthy controls. Voxel-based morphometry was performed by using statistical parametric mapping. The epsilon4 allele frequency was higher in the AD group (P < 0.001) than the controls but not in the bvFTD group. No differences in demographic or cognitive profiles were observed between epsilon4 allele carriers and noncarriers within any of the diagnostic groups. However, epsilon4 carrier status was associated with more severe brain atrophy in disease-specific regions compared with noncarriers in both AD and bvFTD. AD epsilon4 carriers showed greater atrophy in the bilateral parietal cortex and right hippocampus, and bvFTD epsilon4 carriers demonstrated greater atrophy in the bilateral medial, dorsolateral, and orbital frontal cortex, anterior insula, and cingulate cortex with right predominance. This regional epsilon4 effect is consistent with the hypothesis that apoE may affect the morphologic expression uniquely in different neurodegenerative diseases. The atrophy patterns in epsilon4 carriers may indicate that they are at greater risk for clinical progression.

MTHFR 677C → T genotype disrupts prefrontal function in schizophrenia through an interaction with COMT 158Val → Met

Understanding how risk genes cumulatively impair brain function in schizophrenia could provide critical insights into its pathophysiology. Working memory impairment in schizophrenia has been associated with abnormal dopamine signaling in the prefrontal cortex, which is likely under complex genetic control. The catechol-O-methyltransferase (COMT) 158Val --> Met polymorphism (rs4680), which affects the availability of prefrontal dopamine signaling, consistently stratifies prefrontal activation during working memory performance. However, the low-dopamine COMT 158Val allele does not confer increased risk for schizophrenia, and its effects on prefrontal function are not specific to the disorder. In the setting of other genetic variants influencing prefrontal dopamine signaling, COMT 158Val --> Met genotype may exert disease-specific effects. A second polymorphism, methylenetetrahydrofolate reductase (MTHFR) 677C --> T (rs1801133), has been associated with overall schizophrenia risk and executive function impairment in patients, and may influence dopamine signaling through mechanisms upstream of COMT effects. We found that the hypofunctional 677T variant was associated with decreased working memory load-dependent activation in the prefrontal and insular cortices in 79 schizophrenia patients, but not in 75 demographically matched healthy controls. Further, significant MTHFR x COMT genotype interactions were observed, which differed by diagnostic group: Reduced prefrontal activation was associated with the 677T and 158Val alleles in patients, but with 677C/C and 158Met/Met genotype in controls. These findings are consistent with epistatic effects of the COMT and MTHFR polymorphisms on prefrontal dopamine signaling, and suggest that in schizophrenia patients, the MTHFR 677T allele exacerbates prefrontal dopamine deficiency. The findings also suggest the importance of weighing COMT effects on prefrontal function within the context of MTHFR genotype.

Unique ERα Cistromes Control Cell Type-Specific Gene Regulation

Estrogens play an important role in normal physiology and in a variety of pathological states involving diverse tissues including breast and bone. The mechanism by which estrogens exert cell type- and disease-specific effects, however, remains to be explained. We have compared the gene expression profile of the MCF7 breast cancer cell line with that of the osteoblast-like cell line U2OS-ERalpha by expression microarrays. We find that fewer than 10% of the 17beta-estradiol (E2)-regulated genes are common to both cell types. We have validated this in primary calvarial osteoblasts. To dissect the mechanism underlying the cell type-specific E2 regulation of gene expression in MCF7 and U2OS-ERalpha cells, we compared the ERalpha binding sites on DNA in the two cell types by performing chromatin immunoprecipitation (ChIP) on genomic tiling arrays (ChIP-on-chip). Consistent with the distinct patterns of E2-regulated gene expression in these two cell lines, we find that the vast majority of ERalpha binding sites are also cell type specific and correlate both in position and number with cell type-specific gene regulation. Interestingly, although the forkhead factor FoxA1 plays a critical role in defining the ERalpha cistrome in MCF7 cells, it is not expressed in U2OS-ERalpha cells, and forkhead motifs are not enriched in the ERalpha cistrome in these cells. Finally, the ERalpha cistromes are correlated with cell type-specific epigenetic histone modifications. These results support a model for the cell type-specific action of E2 being driven primarily through specific ERalpha occupancy of epigenetically marked cis-regulatory regions of target genes.

P3-282: Apolipoprotein E4 allele and grey matter atrophy in frontotemporal dementia and Alzheimer's disease: A disease-specific regional effect

P3-282: Apolipoprotein E4 allele and grey matter atrophy in frontotemporal dementia and Alzheimer's disease: A disease-specific regional effect

Family Functioning in Children with Chronic Illness Compared with Healthy Controls: A Critical Review

dvances in medical care and technology have increased the lifespan and decreased the disease-related suffering of children with chronic illnesses. In addition to physical health outcomes, health care professionals are increasingly evaluating other parameters, such as child and family adjustment. Among these psychosocial factors, family functioning s a key variable that has been shown to play an essential role in children’s adjustment to chronic illness. Family functioning is a broad concept and is often used as an umbrella term encompassing numerous constructs, ncluding parents’ satisfaction with their parenting role, positive parent– child interactions, family communication, family daptability, and family cohesion. Research has shown that families of a child with a chronic illness may have deficits in amily cohesion, family adaptability, parent-child interactions, family conflict, and family problem-solving skills. nderstanding the nature and development of these problems in family functioning is critical to formulating effective nterventions. Although we know that family functioning is related to the well-being of children with chronic illness, we lack a clear nderstanding of whether families of chronically ill children are significantly more likely to have difficulties in functioning ompared with families of healthy children. In this article we review the research into the functioning of families with children ith a range of chronic illnesses compared with healthy controls, critique these studies, highlight parallels across the literature, nd provide directions for future study. The inclusion of demographically matched healthy control groups allows researchers to eliminate a number of ethodological limitations and draw strong conclusions regarding the impact of childhood illness on family functioning. his is particularly important with measures of family functioning that were not recently normed, or were normed with group that is significantly different from the sample being studied. For example, researchers examining family functioning n the predominately African-American sickle cell disease (SCD) population have stressed the importance of including a emographically matched healthy comparison sample rather than relying on the norm-group statistics for comparisons. ncluding this group allows researchers to better distinguish the disease-specific effects on family functioning independent rom the sociocultural influences, such as ethnic minority socioeconomic status. A review of studies of chronic illness djustment and family functioning indicates that previously established differences are not significant when healthy ontrols are included. We selected cystic fibrosis (CF), juvenile rheumatoid arthritis (JRA), type 1 diabetes/juvenile-onset diabetes, asthma, emophilia, and SCD for this review because these are some of the most common chronic childhood illnesses and represent a road spectrum of disease. Although there are differences across these 6 groups, there are imilarities in chronicity, creation of disability, and need to adhere to demanding regiens.

Low bone mineral density is related to severity of chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) appears to be associated with low bone mineral density (BMD). BMD loss can be accelerated by a number of factors associated with COPD, but it is not known whether COPD itself has a direct effect. Our aim was to investigate in a cross-sectional study whether COPD patients have lower BMD than healthy individuals, and whether the severity of the disease affects BMD. Eighty-eight COPD patients attending a rehabilitation program were classified into stages II, III and IV using GOLD criteria. BMD was measured by dual X-ray absorptiometry in lumbar spine (L2–4), femoral neck (FN) and total body (TB). Values were converted to Z-scores (adjusted for age and sex). Associations between Z-scores and steroid use, body mass index, pack-years and six-min walking distance were analyzed. The Z-scores (mean and (CI)) for all patients were for L2–4: − 0.6 (− 0.9, − 0.3), FN: − 0.8 (− 1.0, − 0.5) and TB: − 0.5 (− 0.8, − 0.2). All scores were significantly different from those of a control population ( p < 0.001). For all three variables (ZL2–4, ZFN, ZTB) there were significant differences between the stages. The difference for ZL2–4 was still significant after adjustment for risk factors. We conclude that BMD is low in COPD patients and decreases with increasing severity of the disease. Low BMD may to some extent be a disease-specific effect.

Impact of smoke-free workplace legislation on exposures and health: possibilities for prevention

The aims of this study were to review experiences with national or statewide smoke-free workplace legislation and data on the occurrence of environmental tobacco smoke (ETS) exposure at work, to present the best estimates for health effects related to workplace ETS exposure, and to calculate corresponding population attributable fractions (PAFs) for respiratory and cardiovascular diseases for 14 European countries and the USA. Systematic searches of the Medline database were carried out, with a cut-off date of November 2005. PAFs for the main outcomes were calculated from the best disease-specific effect estimates and country-specific prevalences of work ETS exposure. Significant numbers of workers are exposed to ETS at work, i.e. approximately 7.5 million workers in 15 European Union countries and 24.6 million in the USA. Workplace ETS exposure is causally linked to lung cancer and coronary heart disease, and is related to an increased risk of asthma in adults and reduced birthweight in newborns. Relatively strong evidence links ETS exposure to chronic obstructive pulmonary disease and stroke. PAFs in Europe and the USA showed that, at current workplace ETS exposure prevalences, the public health impact is substantial. Experience of national and statewide smoke-free workplace legislation from different countries shows that such legislation leads to significant reductions in employees' environmental tobacco smoke exposure at work, as well as improvements in respiratory and cardiac health.

Psychosocial consequences of prostate cancer: 30 years of research

Carcinoma of the prostate is the leading source of solid-organ cancer in U.S. men. When the disease is discovered early, survival rates are high; survivorship, however, is commonly complicated by disease-specific treatment side effects that challenge a man's physical, mental, and social well-being and life satisfaction. This review comprises a search of scientific literature published between 1970 and March 2004 with the aims of 1) identifying the terms used to define the psychosocial consequences unique to men treated for prostate cancer and 2) describing the research aimed at improving the lives of survivors through psychosocial interventions.

Dose dependent effect of APOE ɛ4 on behavioral symptoms in frontal lobe dementia

To determine whether apolipoprotein alleles (APOE) influence behavioral and psychological signs and symptoms of dementia (BPSD), we initiated a prospective, longitudinal study. Patients with Alzheimer's disease (AD) ( N = 186), frontotemporal dementia (FTD) ( N = 29), mixed dementia (MXD) ( N = 28), dementia with Lewy bodies (DLB) ( N = 11) and Parkinson's disease dementia (PDD) ( N = 7) were included. Blood was collected for DNA extraction and APOE genotyping. Behavioral assessments were performed at baseline and semi-annually thereafter, using behavioral assessment scales (Middelheim frontality score, behavioral pathology in Alzheimer's disease rating scale (Behave-AD)). In FTD patients, we identified dose dependent effects of APOE ɛ4 on the Behave-AD total and cluster aggressiveness scores. APOE ɛ2 was associated with a higher score on the Behave-AD cluster delusions in PDD/DLB patients. No APOE effects on frequency or severity of BPSD in AD and MXD patients were found. In conclusion, APOE has disease-specific effects on BPSD in FTD and PDD/DLB patients, given the reported associations of APOE ɛ4 with aggression (FTD) and of APOE ɛ2 with delusions (PDD/DLB).

Urotensin II: A Vascular Mediator in Health and Disease

Urotensin II is the most potent vasoconstrictor known. Paradoxically, urotensin II also possesses vasodilator activity in certain vascular beds. While much is still to be learnt regarding urotensin II's actions on vascular tone, it is now clear that it mediates its effects by interacting with a specific G-protein-coupled receptor. The presence of urotensin II and its receptor in both vertebrate and invertebrate species suggests an evolutionarily conserved role in normal physiology although evidence is mounting for both species-specific as well as disease-specific effects of this peptide. This somatostatin-like peptide was originally thought to reside solely in compartments of the central nervous system. However, recent evidence implicated urotensin II in the pathogenesis of a variety of disease processes ranging from hypertension to hepatic cirrhosis. Increased expression of this peptide has been noted in cardiac, renal and hepatic disease. While the contribution of urotensin II to these diseases remains unclear, the advent of urotensin II antagonists allows for not only the possibility of a new range of therapeutic drugs but also new avenues of investigation and further mechanistic insights into the pathophysiology of these disease processes.

P4.014 Galantamine improves attention in patientswith mild to moderate Alzheimer's disease

To determine whether apolipoprotein alleles (APOE) influence behavioral and psychological signs and symptoms of dementia (BPSD), we initiated a prospective, longitudinal study. Patients with Alzheimer's disease (AD) (N = 186), frontotemporal dementia (FTD) (N = 29), mixed dementia (MXD) (N = 28), dementia with Lewy bodies (DLB) (N = 11) and Parkinson's disease dementia (PDD) (N = 7) were included. Blood was collected for DNA extraction and APOE genotyping. Behavioral assessments were performed at baseline and semi-annually thereafter, using behavioral assessment scales (Middelheim frontality score, behavioral pathology in Alzheimer's disease rating scale (Behave-AD)).In FTD patients, we identified dose dependent effects of APOE ɛ4 on the Behave-AD total and cluster aggressiveness scores. APOE ɛ2 was associated with a higher score on the Behave-AD cluster delusions in PDD/DLB patients. No APOE effects on frequency or severity of BPSD in AD and MXD patients were found.In conclusion, APOE has disease-specific effects on BPSD in FTD and PDD/DLB patients, given the reported associations of APOE ɛ4 with aggression (FTD) and of APOE ɛ2 with delusions (PDD/DLB).