Elderly Demented Patients Research Articles

The risk of bone fractures in dementia patients receiving acetylcholinesterase inhibitors: a meta-analysis.

The authors aimed to conduct a meta-analysis to determine if acetylcholinesterase inhibitors may pose a direct threat, increasing the incidence of fractures in dementia patients. PubMed, Scopus, and Cochrane Library were searched. Inclusion criteria were any original studies that demonstrated the link between acetylcholinesterase inhibitors and the incidence of fracture in patients with dementia. RevMan(5.4) was used. Seven observational studies were included. The total number of patients included in the acetylcholinesterase inhibitors group is 274332 and 290347 in the control group. The pooled analysis showed that the risk of bone fracture was not statistically different between dementia patients who received acetylcholinesterase inhibitors and those who did not receive them (odds ratio=1.44, CI 0.95, 2.19, P=0.09). Subgroup analysis showed no statistically significant difference between dementia patients who took acetylcholinesterase inhibitors, and those who didn't take acetylcholinesterase inhibitors in those more than or equal to 80 years old and those less than 80 years old (P=0.44) and (P=0.34) respectively. However, our results showed a statistically significant association between dementia patients who received acetylcholinesterase inhibitors and decreased fracture risk in those receiving the treatment for more than or less than 2 years (risk ratio=0.48, CI= 0.45, 0.51, P<0.00001) and (risk ratio=0.84, CI 0.70, 0.99, P=0.04), respectively. Our study revealed no role for acetylcholinesterase inhibitors in increasing the risk of fracture compared with controls. Hence, based on our analysis, they might have a protective role against fracture when used for long periods considering their positive action on bone growth and development. Therefore, Acetylcholinesterase inhibitors could be considered a safe option for improving cognitive functions in elderly demented patients without carrying any additional risks.

Blunt Traumatic Brain Injury and Alzheimer Pathology

Introduction: Traumatic brain injury (TBI) has been associated with a greater risk of late-life dementia, including Alzheimer’s disease (AD), but only a few studies examined the relationship between residuals of blunt TBI and autopsy-proven AD. The objective of the present study was to examine the incidence of fully developed AD pathology after documented blunt TBI, and the frequency of residuals of blunt TBI in a series of cases with definite AD. Methods: Among a sample of 1,750 consecutive autopsy cases of elderly demented patients, those cases with residuals of blunt (closed) TBI and definite AD pathology were assessed, and among 933 individuals with autopsy-proven AD, those with residuals of blunt TBI were selected. Results: Among 190 autopsy cases with residuals of blunt TBI, 28 (14.7%; mean age 77.2 ± 10.6 years) revealed the pathological features of definite AD (Braak stage V or VI; ABC 3/3/3), while among 1,150 elderly controls (Braak stage < IV, mean age 77.3 ± 9.5 years), 160 (13.6%) showed residuals of blunt TBI. The second part of the study included 933 consecutive cases with definite AD (Braak stage V or VI; ABC 3/3/3, mean age 82.3 ± 8.4 years), in which 30 cases (3.3%; mean age 77.8 ± 10.7 years) showed morphological residuals of blunt TBI. Conclusion: The results of this retrospective study, on the one hand, did not support the idea that blunt TBI and its morphological residuals are responsible for the development of definite AD, whereas the second part of the study, showing morphological residuals of blunt TBI among 3.3% of definite AD cases were similar to the results in a clinical series who sustained moderate to severe TBI. Considering these conflicting results, further studies on the relationship between the severity and location of morphological residuals of blunt TBI and the development of AD pathology are warranted.

Assessment of serum Levels of Adiponectin and Leptin in a cohort of elderly Egyptian Patients with Dementia

Background/Aim: Dementia is a chronic progressive deterioration of cognitive function. About 50 million cases of dementia worldwide, 5-8% of elders aged 60 years and more have dementia. Adiponectin is an adipokine and presents in the humans’ brains and is linked to multiple functions in the central nervous system. Leptin is a cytokine that was thought to be associated with a decline in cognitive function. The present study aimed to assess adiponectin and leptin levels in elderly demented patients. Materials and methods: the current study included 60 subjects of both genders aged 65 years and more; Group (I): 40 patients with dementia, and Group (II): 20 healthy control subjects. We excluded participants with chronic renal or hepatic diseases, diabetics, hypertensive, dyslipidemic patients, those with thyroid disorders, and those who were morbidly obese. MMSE and MOCA tests were done on all subjects, levels of adiponectin and leptin were assessed in participants’ sera using the ELISA test. Results: Higher levels of adiponectin, but low levels of leptin were detected in patients with dementia. MMSE and MOCA scores were significantly correlated with serum adiponectin (negatively), and with serum leptin (positively). Conclusion: In elderly patients with dementia, serum adiponectin and leptin were strongly associated with the degree of dementia, which may help us to understand the underlying pathophysiology of this untreatable disease.

Factors influencing length of hospital stay in an acute psychogeriatric unit.

Dementia patients represent a significant volume of hospital admissions and impose a high cost on the health system. There is a significantly higher length of hospital stay (LOHS) for elderly demented patients. This study was carried out in an acute psychogeriatric unit specialising in behavioural and psychological symptoms in dementia. Socio-demographic, cognitive and nutritional variables were taken into account. We first compared the patients returning home (group 1) after hospital discharge with those transferred to the rehabilitation psychogeriatric unit (group 2). We secondarily explored the correlation of LOHS with the variables described above for the two groups. We retained 92 patients (of 375 admitted) for our study, mean age 83.9 ± 6.6, Mini-Mental State Examination 12.8 ± 9.6, initial weight 61.7 ± 13.2 kg and body mass index 24.8± 4.7. We noticed significant differences in cognitive status but not in nutritional variables or in socio-demographic characteristics between the two groups. Only weight in nutritional variables was significantly associated with LOHS in the acute psychogeriatric unit. Our main finding underlined the key role of cognitive factors in patient discharge home. And only initial weigh seems have an influence in LOHS instead of cognitive status or socio-demographic characteristics.

Tolerability of Midazolam to treat acute agitation in elderly demented patients: A systematic review.

Behavioural disorders are difficult to manage in elderly demented patients because of the lack of appropriate drugs or difficulties surrounding the route of administration. The tolerability of Midazolam is well described in the emergency management of agitation for young patients, when administered intramuscularly or intravenously. However, very little data are available on the use of oral Midazolam for this indication and in the elderly population. A literature review was conducted, and studies were included if involving adults, receiving Midazolam, alone or in combination, whatever the route, dosage or indication and if they reported adverse events related to the use of Midazolam. Forty-one articles were included. Eleven different adverse events were identified from the studies. Hypotension and desaturation were the two most frequent adverse events reported. Adverse reactions appear to be more common in older patients but also when Midazolam was used in combination with other drugs. The frequency of these adverse effects was lower than those reported for neuroleptic drugs. The oral route appears to be appropriate to provide a rapid and well-tolerated response. Further studies will be needed to confirm the good tolerance of oral Midazolam in the management of acute agitation in elderly demented patients.

Measurement of Care-Related Needs of Family Members Caring for Demented Elderly Patients at Home

Measurement of Care-Related Needs of Family Members Caring for Demented Elderly Patients at Home

Prevalence of Depression among Caregivers of Dementia Patients

Background: Depression is a common problem af fecting caregivers of dementia pat ients . Factors such asc ar egi v e rs ’ ag e, g en de r, ed ucational level , mari tal status and financial status may play a role in care givingrelated depressive disorder.Aim: to detect the prevalence of depression among caregivers .Methods: The study included 96 caregivers for demented elderly patients. Depression among caregivers was assessed using PHQ-9 scaleResults: T he c a r egi v e rs ’ m ea n ag e was (4 2. 94 ) ± 1 3.1 7 y e a rs . (69.7%) of the care givers were women. More than hal f of them (52%) were mar ried. (38.5%) of caregivers had moderate to severe depression, (43.7%) had mi ld to moderate depression and (17.7%) were wi th minimal depressive symptoms .Conclusions: Caregivers of patients wi th dementia are prone to depression and physical ai lments. Caregiverfactors predicting l iabi l i ty to caregiver burden are c a re gi v e r ’ s fi n anc i al s t at us , c a re gi v e r’ s ed uc a ti o n l ev el am on gother socio-demographic variables.

S32 Investigation method of neurodegeneration through brain connectivity modulation

Human behavior and cognition are characterized by engagement of functional distributed networks within the brain. Such networks organization is especially significant for higher functions including abstract reasoning, memory and action planning and requires a high degree of intra-modal and inter-modal integration of information flow arriving from several, different and often remote brain sources. It will be reported the topological changes in functional brain networks during physiological and pathological aging by graph theoretical analysis of resting-state EEG recordings. Furthermore, evidences illustrate possible way to investigated neurodegeneration such as in Alzheimer’s disease through the study of the brain connectivity modulation. Theoretical graph approach is a promising tool, able to catch some global and local features in the functional connectivity patterns estimated from the EEG along the physiological and pathological brain aging. Applying modern graph theory looking for EEG pathological brain aging from both cortical sources powers and connectivity to a large cohort allowed us to demonstrate a continuous line connecting normal elderly subjects and demented patients passing through MCI. Altogether, we concluded that coupling measures can discriminate cortical network features distinguishing physiological from pathological neurodegenerative brain aging.

Evidence and decision algorithm for the withdrawal of antipsychotic treatment in the elderly with dementia and neuropsychiatric symptoms.

Antipsychotics (APs) are commonly used to manage neuropsychiatric symptoms (NPS) in elderly patients with dementia, even though several large studies have demonstrated an association between AP treatment and increased morbidity and mortality in people with dementia. The aim of this study is to review the scientific literature of the use of AP in the elderly with dementia and to propose an algorithm to assist in decision-making regarding the withdrawal of APs. A computerized literature search (MEDLINE: 1966 to December 2016, EMBASE: 1982 to December 2016) was used to locate relevant literature. Keywords in the search included terms from Medical Subject Headings (MESH) and EMBASE thesaurus (EMTREE). The following terms were used in the MESH database and EMTREE thesaurus: Aged, Antipsychotic Agents, Behavioral Symptoms and Dementia. Earlier studies of APs used in elderly patients with dementia suggest that, in most elderly demented patients, APs can be withdrawn with no effect on behaviour. These patients are likely to benefit from the algorithm we propose to assist clinicians in the withdrawal of APs. In this paper, we review the potential risks and benefits of discontinuing AP treatment in elderly demented patients with NPS and propose an algorithm to assist in decision-making regarding AP withdrawal.

The US Food and Drug Administration's Perspective on the New Antipsychotic Pimavanserin.

To summarize the US Food and Drug Administration's (FDA's) review of the safety and effectiveness for pimavanserin, an atypical antipsychotic, for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis. We describe the regulatory and clinical issues important to the FDA's approval of this New Drug Application, with special focus on the risk-benefit balance. We also describe a new labeling feature that presents additional efficacy data to clinicians. Data sets for all relevant clinical trials of pimavanserin and the Applicant's and FDA's analyses of these data were considered in this review. Data were available from 616 patients with Parkinson's disease with hallucinations and delusions who received at least 1 dose of pimavanserin, with a total exposure of 825 patient-years in the Parkinson's disease psychosis population. Pimavanserin 34 mg/d was effective in treating hallucinations and delusions associated with Parkinson's disease. In the Applicant's single pivotal trial, 80.5% of pimavanserin patients experienced at least some improvement in symptoms compared to 58.1% of patients taking placebo. Pimavanserin did not worsen motor function, an adverse effect commonly observed with other antipsychotics, probably because of a lack of consequential dopamine binding. Pimavanserin is the only FDA-approved treatment for the hallucinations and delusions seen in patients with psychosis of Parkinson's disease. Although pimavanserin appears to have a pharmacologic mechanism that is different from other atypical antipsychotics, concern remained that the increased risk of death seen with antipsychotic use in elderly demented patients, and described in all approved antipsychotic labels, would also occur with pimavanserin. Pimavanserin bears the same boxed warning about the risk of death associated with antipsychotic use in elderly patients with dementia.

The first Japanese trial of the community-based integrated care system in a rural area

Introduction: Japan has the highest elderly rate of population in the world. In 2012, the government implemented the community-based integrated care system, which integrates various health-related resources within the community through cooperation among formal, long-term care facilities, welfare and medical care specialists, and informal voluntary activities by the residents. The system was first born in a rural town in Hiroshima.Description of the policy: This presentation shows how a trial in a typical rural town achieved the community-based integrated care system, influenced the governmental policies, and became the first model for the subsequent nationwide reform of healthcare system. In 1970s, the aging population has been prominent in Mitsugi. At that time, care for the elderly was fragmented into various service sections. An integrated care system marshaling all services and providing an integrated delivery system, which was later called the community-based integrated care system, has been gradually constructed in Mitsugi as follows.Firstly, in 1970s, the hospital started providing home-visit services; doctors, nurses, long-term care workers and the like would visit patients’ houses, support their life at home instead of patients coming to the hospital. It promoted linkage between care services in the hospital and at home. Secondly, the Health Management Center was opened as an annex of the hospital in 1984. This center involved some departments of the municipal government, which had been responsible for the preventive, welfare and long-term care services in those days. It enabled the hospital to play a role in not only medical but also preventive, welfare and long-term care services, which facilitated providing these services seamlessly. Thirdly, long-term care facilities such as a nursing home and a group home for demented elderly patients were established. These facilities made long-term care possible for the elderly people that cannot be cared for at home. Lastly, Mitsugi launched volunteers’ action by community citizens to help the elderly with the cooperation of the hospital. This volunteer system has formed the connection between residents and the hospital, which has made more seamless community-cooperative comprehensive care possible.Results: After the system, the proportion of bedridden people decreased remarkably from 3.5 to 1% in this town. In addition, this system realized slowing growth of healthcare costs, while they were then rapidly increasing throughout the rest of Japan. Although healthcare costs for elderly in Mitsugi were above average in Hiroshima prefecture until about 1985, the status has since been reversed, maintaining a lower level than the prefectural mean. After its success, the first community-based integrated care system case in Mitsugi became the model for the national policy implemented in 2012.Highlights: Success in a small rural town can influence the entire country. This is the first case of diffusion of a healthcare system from rural to urban areas, which is unusual. The reasons why the first community-based integrated care system arose in Mitsugi are the aging of the population, easy integration of services due to its small size, the economic support from the prefecture, and existence of a leader that coordinated different sectors of healthcare.Conclusion: There are three future tasks to sustain the community-based integrated care system. Firstly, the system suitable for each community should be constructed. Secondly, vigorous resident participation is needed in this system so that they can find and introduce neighbors that need medical or long-term care services to the system. Finally, finding ways to reduce the costs for medical and long-term care services at a nationwide level.

TNI-93: A New Memory Test for Dementia Detection in Illiterate and Low-Educated Patients.

To validate the TNI-93 test in illiterate and low-educated subjects bysetting cutoff scores to discriminate non-demented and demented subjects in a clinical setting (CESILL) and verifying the adequacy of these cutoff scores in a population-based study (AMI cohort). We used two study samples. First, a clinical setting (CESILL) comprising normal elderly participants and demented patients, mostly multicultural, low educated, or illiterate, was used to compute the cutoff scores of TNI-93 for the detection of dementia. Second, the AMI cohort, a population-based cohort of retired farmers living in a rural setting, was used as a replication study, to assess the detection properties of the cutoff scores in a different population composed mostly of low-educated older people. When combining the two scores, that is, free recall <6 or total recall <9, TNI-93 can detect dementia with a high sensitivity (87%) and specificity (96%), in the CESILL setting. These cutoff scores were roughly similar in the AMI cohort with high sensitivity (80% sensitivity) and specificity (81% specificity). In both study samples, the level of education had no effect on performance. The TNI-93 appears to be a good test to detect dementia. The absence of a significant effect of education level on the performances makes the TNI-93 a tool of choice in the screening of dementia in illiterate/low-educated subjects.

Benefits of Deep Transcranial Magnetic Stimulation in Alzheimer Disease: Case Series.

Patients diagnosed with Alzheimer disease (AD) show severe cognitive deficits. Decline in memory, language, and executive function have repeatedly been reported. Although AD affects 60% to 80% of demented elderly patients, there is currently no cure and limited treatment alternatives. The aim of the study was to evaluate the feasibility of stimulating prefrontal cortex (PFC) with deep transcranial magnetic stimulation (dTMS) to ameliorate cognitive deficits in patients suffering from AD. Eleven patients (6 males; mean [SD] age, 76 [7] years) in moderate to severe stages of AD received dTMS over the PFC for 20 sessions. Computerized battery (Mindstreams [MS]) and neuropsychological testing (Addenbrooke Cognitive Examination [ACE]) were used to assess cognitive performance before and after treatment. Compared with baseline, 60% of patients performed better on the MS battery and 77% of patients performed better on the ACE testing at the end of dTMS treatment. None of the patients performed worse on both tests at the end of treatment. The DTMS effects on the group mean in ACE and MS approached significance (P = 0.065 and P = 0.086, respectively). A dTMS-induced improvement in the ACE was significant (P = 0.001) on patients in more progressed stage (n = 6). Change in ACE negatively correlated with score at baseline. In sum, the current report of this novel technique indicates that deep stimulation might lead to preservation and even improvement of cognitive functions, at least during the time of treatment. Further examinations should report of long-term effects of this technique.

Difference in apolipoprotein E genotype distribution between dentate and edentulous elderly patients with Alzheimer disease

Association between dementia and tooth loss has been shown although the nature of that association is not clear. It has also been shown that risk of dementia was increased in apolipoprotein E4 allele carriers. The objective of this study was to determine the frequency of APOE alleles and their association with the dental status in elderly demented patients. Dental status of 67 patients with dementia was recorded. DNA was isolated from buccal swabs and genotyping was done by PCR-RFLP. The majority of participants had E3/E4 genotype (55.2%) and these heterozygotes were significantly more frequent than any other genotype (p&lt;0.001). There was no significant association between dental status and genotype. However, partial edentulousness with very few teeth in both jaws (1-9 teeth) was significantly more frequent among demented patients with E3/E4 genotype (p=0.021). Patients with Alzheimer disease most frequently had E3/E4 genotype and had very few or no teeth.

Clinical Practice Guideline for the Treatment of Intrinsic Circadian Rhythm Sleep-Wake Disorders: Advanced Sleep-Wake Phase Disorder (ASWPD), Delayed Sleep-Wake Phase Disorder (DSWPD), Non-24-Hour Sleep-Wake Rhythm Disorder (N24SWD), and Irregular Sleep-Wake Rhythm Disorder (ISWRD). An Update for 2015

A systematic literature review and meta-analyses (where appropriate) were performed and the GRADE approach was used to update the previous American Academy of Sleep Medicine Practice Parameters on the treatment of intrinsic circadian rhythm sleep-wake disorders. Available data allowed for positive endorsement (at a second-tier degree of confidence) of strategically timed melatonin (for the treatment of DSWPD, blind adults with N24SWD, and children/ adolescents with ISWRD and comorbid neurological disorders), and light therapy with or without accompanying behavioral interventions (adults with ASWPD, children/adolescents with DSWPD, and elderly with dementia). Recommendations against the use of melatonin and discrete sleep-promoting medications are provided for demented elderly patients, at a second- and first-tier degree of confidence, respectively. No recommendations were provided for remaining treatments/ populations, due to either insufficient or absent data. Areas where further research is needed are discussed.

Overlap syndrome of dementia, depression and delirium in elderly patients: a report of 16 cases

Objective To analyze the clinical characteristics and prognosis of the overlap syndrome of dementia, depression and delirium coexistence in two or three of them (the 2D's or 3D's) in elderly patients, in order to raise awareness. Methods Clinical data of 16 patients aged >65 years diagnosed with the 2D's or 3D's admitted to Peking Union Medical College Hospital from 2010 to 2014 were analyzed and relevant literatures were reviewed. Results Patients with the 2D's or 3D's accounted for 10% of the elderly demented patients and 3% of the elderly depressive patients. 16 patients〔11 females and 5 males, median age 82 years and mean age (80±6) years〕were enrolled, with 7 cases of dementia with depression, 6 cases of delirium superimposed on dementia, 2 cases of the 3D's, and 1 case of coexisting depression and incident delirium. The Charlson comorbidity index of the 16 patients was (3.0±1.5). (4.0±1.6) kinds of geriatric syndromes were found, and the most common were falls (62%), sleep disorders (56%), frailty (50%), polypharmacy (43%), and malnutrition (37%). Disability was identified in 14 (88%) patients on admission. Delirium was observed in 9 patients (56%), with 7 cases of hyperactive delirium and 2 cases of hypoactive delirium. Coexisting underlying dementia was identified after episodes of delirium in 6 cases. 16 patients all received corresponding intervention during hospitalization period. During a mean follow-up period of (15±13) months, 62% of the patients had more impaired physical function (ADL score reduction≥1), and 43% of the patients had more impaired cognitive function (MMSE score reduction≥3). Two patients were transferred to long-term care facilities and one patient died during follow-up. The re-admission rate was 50% within 1 year after discharge. Conclusions The domestic report of overlap syndrome of dementia, depression and delirium is rare. Patients with the coexistence of the 2D's or 3D's are more commonly combined with geriatric syndromes, which results in further cognitive and physical function impairment with a higher re-admission rate. We should pay attention to the follow-up in elderly patients with delirium for screening dementia. Key words: Dementia; Depression; Delirium; Comorbidity

Association of quetiapine with ischemic brain stem stroke: a case report and discussion.

Atypical antipsychotics (AAPs) are approved by the US Food and Drug Administration (FDA) for the treatment of schizophrenia and bipolar disorder. Since the health regulatory agency of Canada (2002), the FDA (2003), and the European Medicines Agency (2004) reported an increased risk of cerebrovascular adverse events (CVAEs) from olanzapine and risperidone in clinical trials of elderly demented patients, there have been concerns about the risk of CVAEs associated with AAPs, and recent guidelines emphasize the importance of generating evidence for AAPs [Shin et al. 2013; Barnes, 2011]. In this article, an ischemic pontine stroke case probably related to quetiapine use is presented. Discussion of the case is of great importance because there are very limited data on the risk of CVAEs associated with the use of quetiapine,

Mortality Risks of Specific Antipsychotics in Dementia

Antipsychotic drugs increase the risks for cerebrovascular events and death in elderly demented patients. To assess mortality risks associated with

Memories of falling in elderly patients with dementia: response concordance rate and reproducibility.

Although demented elderly patients have impaired memory, memories of falling are not uncommon. We aim to clarify reliability of memories of falling in such patients. Subjects included 62 patients (18 men, 44 women) diagnosed with dementia who resided in long-term care facilities. Mean age was 82.9 ± 7.8 years, mean Mini-Mental State Examination score was 16.4 ± 4.7 points, and mean Functional Independence Measure score was 67.9 ± 18.4 points. Subjects were asked a closed question about whether they were aware of having fallen (i.e. memories of falling) over the past year. Fear of falling was quantified using the visual analogue scale and FACES Pain Rating Scale. Scores were re-measured during retest approximately 10 days later to examine reproducibility of memories and fear of falling. Subjects whom staff had witnessed suffering a fall between baseline and retest session were excluded. Fall memory concordance rate was 0.84, visual analogue scale reproducibility (correlation coefficient) was 0.98, and FACES Pain Rating Scale was 0.86. No differences in Mini-Mental State Examination scores were noted between groups for whom memories of falling were or were not reproducible. No correlation was observed among Mini-Mental State Examination, Functional Independence Measure scores, and intensity of fear of falling. There was a high concordance rate for patients' memories of falling, which suggests that falls were retained as memories. No relationship was observed between memories of falling and degree of cognitive impairment, and severe dementia did not necessarily imply memories of falling were unreliable. The reproducibility of fear of falling suggested the intensity of fear of falling was not easily altered. It was possible memories of falling and fear of falling mutually interacted to reinforce and fixate with each other, leading to the observed phenomenon. Therefore, it appeared memories of falling were retained by patients; this fact can be used in fall prevention and vital function maintenance.

On the Discovery and Development of Pimavanserin: A Novel Drug Candidate for Parkinson’s Psychosis

Parkinson’s disease psychosis (PDP) is a condition that may develop in up to 60 % of Parkinson’s patients, and is a major reason for nursing home placement for those affected. There are no FDA approved drugs for PDP but low doses of atypical anti-psychotic drugs (APDs) are commonly prescribed off-label. Only low-dose clozapine has shown efficacy in randomized controlled trials, but all APDs have black box warnings related to the increased mortality and morbidity when used in elderly demented patients. Using molecular pharmacological profiling of a large collection of marketed drugs, we discovered that potent inverse agonist activity against 5-HT2A serotonin receptors was a common feature of atypical APDs, especially the atypical APDs used to treat PDP. Since low-dose clozapine therapy selectively blocks this receptor, it was hypothesized that a highly selective 5-HT2A receptor inverse agonist might provide good symptom control in patients suffering from PDP, with a greatly improved safety and tolerability profile. A high throughput screening and subsequent chemical lead optimization campaign to develop potent, selective 5-HT2A receptor inverse agonists was launched, eventually resulting in the discovery of pimavanserin. Pimavanserin displays nanomolar potency as a 5-HT2A receptor inverse agonist, selectivity for 5-HT2A over 5-HT2C receptors, and no meaningful activity at any other G-protein coupled receptor. It demonstrated robust activity in preclinical models of schizophrenia and PDP, and did not worsen motoric symptoms, in contrast to the APDs tested. In a Phase III clinical trial, pimavanserin showed highly significant benefits in the primary endpoint, the scale for assessment of positive symptoms-PD, a scale adapted for use in PDP. In addition, improvements in all other efficacy endpoints, including physician’s clinical global impression, caregiver burden, night-time sleep quality and daytime wakefulness, were seen. Pimavanserin demonstrated good safety and tolerability and did not worsen motoric symptoms as assessed by the unified Parkinson’s disease rating scale parts II and III. An open-label extension study has further demonstrated that pimavanserin is safe and well-tolerated with long-term use. Pimavanserin may therefore offer a viable treatment option for patients suffering from PDP.