Occurrence Of Neuropsychiatric Symptoms Research Articles

CRP/Neopterin Ratio and Neuropsychiatric Symptoms in Patients with Different Forms of Pneumonia: Results of a Pilot Study.

Pneumonia is one of the most common infectious diseases, mostly caused by viruses or bacteria. In response to bacteria or viruses which are different but which also are partly overlapping, innate and adaptive immune responses are induced, which can be quantified using the determination of specific biomarkers. Among these, C-reactive protein (CRP) has been established as a marker of innate immune function, whereas Neopterin, which is mainly produced upon stimulation with interferon-gamma, reflects cellular immune activation. We investigated inflammation markers in patients with microbiologically confirmed viral or bacterial pneumonia, and studied the potential of CRP, Neopterin, and the CRP/Neopterin ratio to distinguish between viral and bacterial pathogenesis. Furthermore, we examined, how often neuropsychiatric symptoms occur in patients suffering from different kinds of pneumonia. A total of 194 patients diagnosed with either coronavirus disease 2019 (COVID-19) (n = 63), bacterial pneumonia (n = 58), Influenza infection (n = 10), Influenza and a bacterial superinfection (n = 9), and COVID-19 patients with a bacterial superinfection (n = 54) were included in our pilot study. Clinical as well as laboratory parameters were determined shortly after admission. We found significantly higher CRP/Neopterin ratios in patients with bacterial pneumonia (median: 0.34) and lower CRP/Neopterin ratios in patients hospitalized with COVID-19 infection (median: 0.03; p < 0.001). Both in men and in women, the CRP/Neopterin ratio was able to distinguish between viral and bacterial pathogens, but also was able to detect bacterial super-infection (BSI) in subjects with initial viral pneumonia (p < 0.001). Patients with BSI presented with significantly lower CRP/Neopterin ratios (median 0.08) than patients with bacterial infection only (median 0.34; p < 0.001). Interestingly, COVID-19 patients had a decreased physical functioning (as reflected in the ECOG score) and a higher frequency of fatigue (84.1%) and neurological symptoms (54.8%) than patients with pneumonia, due to other underlying pathogens. Patients that reported fatigue during viral and bacterial pneumonia presented with lower CRP concentrations than patients without it. The CRP/Neopterin ratio is useful to differentiate between viral and bacterial pathogenesis. The occurrence of neuropsychiatric symptoms in pneumonia appears to depend on the kind of pathogen causing the infection. Lower CRP concentrations at admission appear to be related to fatigue during acute viral and bacterial infection.

Neuropsychiatric symptoms and ApoE genotype in older adults without dementia: a cross-sectional study.

The ApoE genotype and neuropsychiatric symptoms (NPS) are known risk factors for cognitive decline in older adults. However, the interaction between these variables is still unclear. The aim of this study was to determine the association between the presence of the ApoE ε4 allele and the occurrence of NPS in older adults without dementia. In this cross-sectional investigation we determined the apolipoprotein E (ApoE) genotype of 74 older adults who were either cognitively normal (20.3% / Clinician Dementia Rating Scale (CDR): 0) or had mild cognitive impairment (MCI: 79.7% / CDR: 0.5). We used a comprehensive cognitive assessment protocol, and NPS were estimated by the Neuropsychiatric Inventory-Clinician Rating Scale (NPI-C), Mild Behavioural Impairment-Checklist (MBI-C), Hamilton Rating Scale for Depression (HAM-D), and Apathy Inventory. ApoE ε4 carriers had higher MBI-C total scores than ApoE ε4 noncarriers. Correlations between NPS and ApoE genotype were observed for two NPI-C domains, although in opposite directions: the ApoE ε4 allele was associated with a 1.8 unit decrease in the estimated aberrant motor disturbance score and with a 1.3 unit increase in the estimated appetite/eating disorders score. All fitted models were significant, except for the one fitted for the domain delusions from the NPI-C. Among individuals with amnestic MCI, ε4 carriers presented higher depression score (HAM-D) than noncarriers; in turn, ε4 noncarriers exhibited higher aggression score (NPI-C) than ε4 carriers. Our analyses showed associations between NPS and the presence of the ApoE ε4 allele in two NPI-C domains, despite the sample size. Furthermore, compared to noncarriers, the presence of the ApoE ε4 correlated positively with appetite/eating disorders and negatively with aberrant motor disturbance domain. Examination of the amnestic MCI group displayed significant, although weak, associations. Therefore, ε4 carriers exhibited higher depression scores according to the HAM-D scale compared to ε4 noncarriers. Conversely, ε4 noncarriers had higher scores in the aggression domain of the NPI-C than ε4 carriers.

Amidst an amygdala renaissance in Alzheimer's disease.

The amygdala was highlighted as an early site for neurofibrillary tau tangle pathology in Alzheimer's disease in the seminal 1991 article by Braak and Braak. This knowledge has, however, only received traction recently with advances in imaging and image analysis techniques. Here, we provide a cross-disciplinary overview of pathology and neuroimaging studies on the amygdala. These studies provide strong support for an early role of the amygdala in Alzheimer's disease and the utility of imaging biomarkers of the amygdala in detecting early changes and predicting decline in cognitive functions and neuropsychiatric symptoms in early stages. We summarize the animal literature on connectivity of the amygdala, demonstrating that amygdala nuclei that show the earliest and strongest accumulation of neurofibrillary tangle pathology are those that are connected to brain regions that also show early neurofibrillary tangle accumulation. Additionally, we propose an alternative pathway of neurofibrillary tangle spreading within the medial temporal lobe between the amygdala and the anterior hippocampus. The proposed existence of this pathway is strengthened by novel experimental data on human functional connectivity. Finally, we summarize the functional roles of the amygdala, highlighting the correspondence between neurofibrillary tangle accumulation and symptomatic profiles in Alzheimer's disease. In summary, these findings provide a new impetus for studying the amygdala in Alzheimer's disease and a unique perspective to guide further study on neurofibrillary tangle spreading and the occurrence of neuropsychiatric symptoms in Alzheimer's disease.

Alzheimer's disease and depression in the elderly: A trajectory linking gut microbiota and serotonin signaling.

The occurrence of neuropsychiatric symptoms in the elderly is viewed as an early sign of subsequent cognitive deterioration and conversion from mild cognitive impairment to Alzheimer's disease. The prognosis in terms of both the severity and progression of clinical dementia is generally aggravated by the comorbidity of neuropsychiatric symptoms and decline in cognitive function. Undeniably, aging and in particular unhealthy aging, is a silent "engine of neuropathology" over which multiple changes take place, including drastic alterations of the gut microbial ecosystem. This narrative review evaluates the role of gut microbiota changes as a possible unifying concept through which the comorbidity of neuropsychiatric symptoms and Alzheimer's disease can be considered. However, since the heterogeneity of neuropsychiatric symptoms, it is improbable to describe the same type of alterations in the bacteria population observed in patients with Alzheimer's disease, as well as it is improbable that the variety of drugs used to treat neuropsychiatric symptoms might produce changes in gut bacterial diversity similar to that observed in the pathophysiology of Alzheimer's disease. Depression seems to be another very intriguing exception, as it is one of the most frequent neuropsychiatric symptoms in dementia and a mood disorder frequently associated with brain aging. Antidepressants (i.e., serotonin reuptake inhibitors) or tryptophan dietary supplementation have been shown to reduce Amyloid β-loading, reinstate microbial diversity and reduce the abundance of bacterial taxa dominant in depression and Alzheimer's disease. This review briefly examines this trajectory by discussing the dysfunction of gut microbiota composition, selected bacterial taxa, and alteration of tryptophan and serotonin metabolism/neurotransmission as overlapping in-common mechanisms involved with depression, Alzheimer's disease, and unhealthy aging.

Association of Cerebral Small Vessel Disease Burden with Neuropsychiatric Symptoms in Non-Demented Elderly: A Longitudinal Study.

The links between cerebral small vessel disease (CSVD) burden and neuropsychiatric symptoms (NPS) have not been fully studied. We aimed to explore the associations of the CSVD burden with Neuropsychiatric Inventory (NPI) total scores and its subsyndromes in the elderly without dementia. We investigated 630 non-demented participants from the Alzheimer's Disease Neuroimaging Initiative. All of them had NPI assessments and 3 Tesla MRI scans at baseline and 616 had longitudinal NPI assessments during the follow-up. Linear mixed-effects models were used to investigate the cross-sectional and longitudinal associations of CSVD burden with NPI total scores and its subsyndromes. Higher CSVD burden longitudinally predicted more serious neuropsychiatric symptoms, including NPS (p &amp;lt; 0.0001), hyperactivity (p = 0.0006), affective symptoms (p = 0.0091), and apathy (p &amp;lt; 0.0001) in the total participants. Lacunar infarcts (LIs), white matter hyperactivities (WMHs), and cerebral microbleeds (CMBs) might play important roles in the occurrence of NPS, since they were longitudinally associated with specific neuropsychiatric subsyndromes. LIs contributed to hyperactivity (p = 0.0092), psychosis (p = 0.0402), affective symptoms (p = 0.0156), and apathy (p &amp;lt; 0.0001). WMHs were associated with hyperactivity (p = 0.0377) and apathy (p = 0.0343). However, CMBs were only related to apathy (p = 0.0141). CSVD burden was associated with multiple neuropsychiatric symptoms, suggesting the importance of monitoring and controlling vascular risk factors. Different markers of CSVD were associated with specific subsyndromes of NPS, suggesting that different markers tended to occur in different encephalic regions.

Pharmacological Rescue with SR8278, a Circadian Nuclear Receptor REV-ERBα Antagonist as a Therapy for Mood Disorders in Parkinson’s Disease

SummaryParkinson’s disease is a neurodegenerative disease characterized by progressive dopaminergic neuronal loss. Motor deficits experienced by patients with Parkinson’s disease are well documented, but non-motor symptoms, including mood disorders associated with circadian disturbances, are also frequent features. One common phenomenon is “sundowning syndrome,” which is characterized by the occurrence of neuropsychiatric symptoms at a specific time (dusk), causing severe quality of life challenges. This study aimed to elucidate the underlying mechanisms of sundowning syndrome in Parkinson’s disease and their molecular links with the circadian clock. We demonstrated that 6-hydroxydopamine (6-OHDA)-lesioned mice, as Parkinson’s disease mouse model, exhibit increased depression- and anxiety-like behaviors only at dawn (the equivalent of dusk in human). Administration of REV-ERBα antagonist, SR8278, exerted antidepressant and anxiolytic effects in a circadian time-dependent manner in 6-OHDA-lesioned mice and restored the circadian rhythm of mood-related behaviors. 6-OHDA-lesion altered DAergic-specific Rev-erbα and Nurr1 transcription, and atypical binding activities of REV-ERBα and NURR1, which are upstream nuclear receptors for the discrete tyrosine hydroxylase promoter region. SR8278 treatment restored the binding activities of REV-ERBα and NURR1 to the tyrosine hydroxylase promoter and the induction of enrichment of the R/N motif, recognized by REV-ERBα and NURR1, as revealed by ATAC-sequencing; therefore, tyrosine hydroxylase expression was elevated in the ventral tegmental area of 6-OHDA-injected mice, especially at dawn. These results indicate that REV-ERBα is a potential therapeutic target, and its antagonist, SR8278, is a potential drug for mood disorders related to circadian disturbances, namely sundowning syndrome, in Parkinson’s disease.

Off-label use of ivermectin for COVID-19: Are there any neuropsychiatric effects to be aware of?

Sir, The COVID-19 pandemic has challenged the health systems and medical providers around the world. This emergency has led to the off-label use of different drugs in the treatment of this new disease, such as ivermectin. Nonetheless, the use of ivermectin is still controversial. The repurposing of drugs for the treatment of COVID-19 is a potential good strategy if their effectiveness and safety have been established. The aim of this mini-commentary is to discuss the evidence regarding the use of ivermectin and its effects on behavioral and neurological functioning. Although there are many reports about the effects of ivermectin on animals, we aimed to summarize the evidence to provide guidance to physicians who prescribe ivermectin. This commentary is a summary of available case reports and case series about the use of ivermectin and the occurrence of neuropsychiatric symptoms, retrieved from a PubMed and Web of Science search. The keywords employed were: “neurological symptoms of ivermectin use,” “motor symptoms of ivermectin use,” “behavioral symptoms of ivermectin use,” “affective symptoms of ivermectin use,” and “psychiatric symptoms of ivermectin use.” Ivermectin is an antiparasitic drug with multiple uses in human, as well animal healthcare. It acts on the chloride-dependent channels of glutamate and γ-aminobutyric acid, interrupting neurotransmission in nematodes and arthropods. Its use in animals has shown neurological effects. In mammals, blindness and ivermectin-induced retinopathy have been reported at doses of approximately 22 mg.[1] In humans, there have been reports of serious neurological adverse events (ataxia, tremor, convulsive disorder, confusional state, amnesia, encephalopathy, and coma) observed with the use of ivermectin in the treatment of onchocerciasis (dose range: 3–24 mg).[2] These adverse effects may not be entirely explained by the concomitant loiasis infections (with supportive evidence on the presence of ivermectin in the encephalic tissue in one case, and the recurrence of symptoms on repeated exposure in three cases).[2] Furthermore, secondary delirium has been reported (dose: 12 mg)[3] as well as psychotic episodes (dose: 6 mg)[4] associated with ivermectin use in combination with albendazole. A case of encephalitis has also been reported due to the weekly use of 12 mg of ivermectin for 6 months, with resolution of the encephalitis after hospitalization of the patient and suspension of the drug.[5] This effect could be due to drug interactions and severity of the disease itself. There is scarce literature on the neurological and behavioral effects of ivermectin use in humans. The off-label use of this drug in the treatment of COVID-19 might encourage more research about the therapeutic and side effects of this agent, above all on behavioral, psychological, and neurological factors of patients. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

The association of neuropsychiatric symptoms with regional brain volumes from patients in a tertiary multi-disciplinary memory clinic.

To examine the interaction between structural brain volume measures derived from a clinical magnetic resonance imaging (MRI) and occurrence of neuropsychiatric symptoms (NPS) in outpatient memory clinic patients. Clinical and neuroimaging data were collected from the medical records of outpatient memory clinic patients who were seen by neurologists, geriatric neuropsychiatrists, and geriatricians. MRI scan acquisition was carried out on a 3 T Siemens Verio scanner at Johns Hopkins Bayview Medical Center. Image analyses used an automated multi-label atlas fusion method with a geriatric atlas inventory to generate 193 anatomical regions from which volumes were measured. Regions of interest were generated a priori based on previous literature review of NPS in dementia. Regional volumes for agitation, apathy, and delusions were carried forward in a linear regression analysis. Seventy-two patients had clinical and usable neuroimaging data that were analyzed and grouped by Mini-Mental State Exam (MMSE). Neuropsychiatric Inventory Questionnaire (NPI-Q) agitation was inversely associated with rostral anterior cingulate cortex (ACC) bilaterally and left subcallosal ACC volumes in the moderate severity group. Delusions were positively associated with left ACC volumes in both severe and mild groups but inversely associated with the right dorsolateral prefrontal cortex (DLPFC) in the moderate subgroup. Agitation, apathy, and delusions are associated with volumes of a priori selected brain regions using clinical data and clinically acquired MRI scans. The ACC is an anatomic region common to these symptoms, particularly agitation and delusions, which closely mirror the findings of research-quality studies and suggest its importance as a behavioral hub.

Religiosity and quality of life of individuals with Alzheimer's disease and of caregivers: Relationship with clinical aspects.

ABSTRACTThere are few studies on the religiosity of people with Alzheimer’s disease (PwAD) and caregivers, relation with quality of life (QoL) and clinical aspects.Objective:To assess the religiosity and QoL of 39 PwAD and their caregivers; to compare perceived QoL and religiosity of the PwAD with those of their caregivers; to associate QoL and religiosity with the presence of neuropsychiatric symptoms, and depression with cognitive performance of PwAD.Results:Organizational religiosity was greater in caregivers. The AD patients had poorer perceived QoL than their caregivers. Caregiver religiosity correlated with that of the AD patients. Higher intrinsic religiosity was associated with lower occurrence of neuropsychiatric symptoms. Better caregiver QoL correlated with cognitive performance. Lower occurrence of depression correlated with better QoL of the caregivers and AD patients.Conclusion:The religiosity of caregivers was correlated with that of the AD patients. Better QoL and lower religiosity were observed in caregivers when compared with the AD patients. Caregiver religiosity and QoL were associated with neuropsychiatric and cognitive aspects and depression.

Oseltamivir-induced neuropsychiatric symptoms

Oseltamivir is a viral neuraminidase enzyme inhibitor commonly prescribed for prevention and management of influenza. Common adverse effects of oseltamivir are gastrointestinal side effects such as nausea, vomiting, diarrhea, and pain abdomen; others are headache, insomnia, cough, skin rashes, and sadness. In 2006, US Food and Drug Administration added a warning to the label of oseltamivir drawing attention to the risk of developing neuropsychiatric adverse events (NPAE). However, the incidence of NPAE with oseltamivir has been underreported in India. Hence, in our report, we present the occurrence of neuropsychiatric symptoms such as aggressive behavior, restlessness, hallucinations, paranoid ideas, and insomnia following administration of oseltamivir in a young adult female patient.

Total testosterone and neuropsychiatric symptoms in elderly men with Alzheimer's disease.

IntroductionThere has been a significant increase in the use of testosterone in aging men, but little investigation into its impact on men with Alzheimer’s disease (AD). The findings of the few studies that have been done are inconsistent. In the present study, we investigated the relationship between total testosterone (TT) and neuropsychiatric symptoms (NPS) in a well-characterized sample of elderly men with mild to moderate AD.MethodsThe sample, which was drawn from the Texas Alzheimer’s Research Care Consortium Longitudinal Research Cohort, included 87 men who met the criteria for mild to moderate AD. The occurrence of NPS was gathered from caregivers and/or family members with the Neuropsychiatric Inventory. TT was analyzed, and the sample was divided into a low-testosterone group (TT ≤2.5 ng/ml; n = 44) and a borderline/normal group (TT ≥2.6 ng/ml; n = 43).ResultsTT was correlated with symptoms of hallucinations, delusions, agitation, irritability and motor activity. The borderline/normal group was significantly more likely to have hallucinations (odds ratio (OR) = 5.56), delusions (OR = 3.87), motor activity (OR = 3.13) and irritability (OR = 2.77) than the low-testosterone group. Health status and apolipoprotein E ε4 status were not significant factors.ConclusionsThe findings of the present study have implications for the use of testosterone replacement therapy in men with AD or the prodromal stage of the disease.

Total Cholesterol and Neuropsychiatric Symptoms in Alzheimer's Disease: The Impact of Total Cholesterol Level and Gender

Background: Neuropsychiatric symptoms (NPS) in Alzheimer's disease (AD) are a major factor in nursing home placement and a primary cause of stress for caregivers. Elevated cholesterol has been linked to psychiatric disorders and has been shown to be a risk factor for AD and to impact disease progression. The present study investigated the relationship between cholesterol and NPS in AD. Methods: Data on cholesterol and NPS from 220 individuals (144 females, 76 males) with mild-to-moderate AD from the Texas Alzheimer's Research and Care Consortium (TARCC) cohort were analyzed. The total number of NPS and symptoms of hyperactivity, psychosis, affect and apathy were evaluated. Groups based on total cholesterol (TC; ≥200 vs. <200 mg/dl) were compared with regard to NPS. The impact of gender was also assessed. Results: Individuals with high TC had lower MMSE scores as well as significantly more NPS and more symptoms of psychosis. When stratified by gender, males with high TC had significantly more NPS than females with high TC or than males or females with low TC. Conclusion: The role of elevated cholesterol in the occurrence of NPS in AD appears to be gender and symptom specific. A cross-validation of these findings will have implications for possible treatment interventions, especially for males with high TC.

Neurobiology of neuropsychiatric symptoms in Alzheimer's disease: A critical review with a focus on neuroimaging.

The objective of this critical review of the literature was to reveal the neural circuits involved in the occurrence of neuropsychiatric symptoms (NPS) in Alzheimer's disease (AD) patients through the association of these symptoms with neuroimaging findings. The search for articles was performed on PUBMED from January 2000 to May 2013, using the key words: Dementia AND BPSD; Dementia AND Neuropsychiatric Symptoms; and Dementia AND Psychosis, Delusions, Hallucinations, Agitation, Depression, Anxiety, Apathy, Euphoria, Disinhibition, Irritability, Aberrant Motor Behavior, Sleep or Eating Disorders. Forty-six articles were reviewed and important contributions, especially regarding the psychopathological concepts discussed, were also considered even if not included in this time period. The available evidence suggests the three most relevant neurobiological models for neuropsychiatric symptoms in Alzheimer's disease are the frontal-subcortical circuits, the cortico-cortical networks, and the monoaminergic system. We discussed the association of the individual symptoms or syndromes with these models.

Biomarkers of Vascular Risk, Systemic Inflammation, and Microvascular Pathology and Neuropsychiatric Symptoms in Alzheimer's Disease

Numerous serum and plasma based biomarkers of systemic inflammation have been linked to both neuropsychiatric disorders and Alzheimer's disease (AD). The present study investigated the relationship of clinical biomarkers of cardiovascular risk (cholesterol, triglycerides, and homocysteine) and a panel of markers of systemic inflammation (CRP, TNF-α, IL1-ra, IL-7, IL-10, IL-15, IL-18) and microvascular pathology (ICAM-1, VCAM-1) to neuropsychiatric symptoms in a sample with mild AD. Biomarker data was analyzed on a sample of 194 diagnosed with mild to moderate probable AD. The sample was composed of 127 females and 67 males. The presence of neuropsychiatric symptoms was gathered from interview with caretakers/family members using the Neuropsychiatric Inventory. For the total sample, IL-15, VCAM (vascular adhesion molecule), and triglycerides were significantly and negatively related to number of neuropsychiatric symptoms, and total cholesterol and homocysteine were positively related and as a group accounted for 16.1% of the variance. When stratified by gender, different patterns of significant biomarkers were found with relationships more robust for males for both total symptoms and symptom clusters. A combination of biomarkers of systemic inflammation, microvascular pathology, and clinical biomarkers of cardiovascular risk can account for a significant portion of the variance in the occurrence of neuropsychiatric symptoms in AD supporting a vascular and inflammatory component of psychiatric disorders found in AD. Gender differences suggest distinct impact of specific risks with total cholesterol, a measure of cardiovascular risk, being the strongest marker for males and IL-15, a marker of inflammation, being the strongest for females.

Effectiveness of Physio Acoustic Sound (PAS) therapy in demented nursing home residents with nocturnal restlessness: study protocol for a randomized controlled trial

BackgroundMany older people with neuropsychiatric disorders such as Alzheimer's disease and frontotemporal dementia suffer from sleeping problems and often show nocturnal restlessness. Professionals and informal carers face considerable problems in solving these problems. Attempts to diminish these problems with medication in a safe and responsible manner have proven hardly effective or not effective at all. Therefore, nowadays the focus lies more on non-pharmacological solutions, for example by influencing environmental factors. There are indications that treatment with low-frequency acoustic vibrations, that is Physio Acoustic Sound (PAS) therapy, has a positive effect on sleeping problems. Therefore we study the effectiveness of PAS therapy in demented patients with nocturnal restlessness.MethodsIn a randomized clinical trial, 66 nursing home patients will be divided into two groups: an intervention group and a control group. For both groups nocturnal restlessness will be measured with actiwatches during a period of six weeks. In addition, a sleep diary will be filled in.For the intervention group the baseline will be assessed, in the first two weeks, reflecting the existing situation regarding nocturnal restlessness. In the next two weeks, this group will sleep on a bed identical to their own, but with a mattress containing an in-built PAS device. As soon as the patient is lying in bed, the computer programme inducing the vibrations will be switched on for the duration of 30 min. In the last two weeks, the wash-out period, the measurements of the intervention group are continued, without the PAS intervention.During the total study period, other relevant data of all the implied patients will be recorded systematically and continuously, for example patient characteristics (data from patient files), the type and seriousness of the dementia, occurrence of neuropsychiatric symptoms during the research period, and the occurrence of intermittent co-morbidity.DiscussionIf PAS therapy turns out to be effective, it can be of added value to the treatment of nocturnal restlessness in demented patients. Non-pharmacological PAS therapy is not only safe and patient-friendly, but it can also be widely used in a simple and relatively inexpensive way, both in institutions such as nursing homes and residential homes for the elderly, and at home. Ultimately, this may lead to a decrease in the frequent and still common use of psychotropic drugs. In addition, care needs of demented patients also may decrease as well as the number of preventable admissions to care institutions.Trial registrationNetherlands Trial Register (NTR): NTR3242

Aligning the evidence with practice: NICE guidelines for drug treatment of Alzheimer’s disease

. More than half of these individuals have Alzheimer’s disease (AD), resulting in a progressive decline in cognition, function and commu-nication, together with the frequent occur-rence of neuropsychiatric symptoms. In addition to the enormous human costs to the individuals and their families, demen-tia costs the global economy GB£604 bil-lion a year

Occurrence of neuropsychiatric symptoms and psychiatric disorders in mild Alzheimer's disease and mild cognitive impairment subtypes

Neuropsychiatric disorders are common in cognitively impaired older persons, and associated with institutionalization and caregiver stress in Alzheimer's disease (AD). Few studies have compared the occurrence of both psychiatric disorders and neuropsychiatric symptoms in patients with AD and mild cognitive impairment (MCI) subtypes. We aimed to investigate the frequency of psychiatric disorders and neuropsychiatric symptoms in AD and MCI patients, compared to controls. We included 245 outpatients of a memory clinic in Rome, Italy (119 AD; 68 multidomain-MCI; 58 amnestic-MCI) and 107 controls. Categorical disorders of depression and apathy were diagnosed with structured interviews. Symptoms were evaluated with the Neuropsychiatric Inventory (NPI). The odds ratios (OR) of patients having neuropsychiatric symptoms compared to controls were calculated with logistic regression, adjusted for sociodemographic and clinical variables. A large proportion of AD (49.6%) and multidomain-MCI (44.1%) patients had depression disorder. Apathy disorder was common in AD (51.3%) but less frequent in amnestic-MCI (6.9%) and multidomain-MCI (14.7%). AD patients were three times more likely to have depression disorders (OR = 3.0, CI = 1.1-7.6) or apathy (OR = 16.9, CI = 4.6-61.8) compared to amnestic-MCI, and seven times more likely to have apathy disorder than multidomain-MCI (OR = 7.5, CI = 3.0-19.2). After apathy and depression, the most prevalent neuropsychiatric symptoms in AD and MCI were anxiety, agitation, irritability, night-time behaviors, and appetite disturbances. There was an increasing prevalence of many neuropsychiatric symptoms with increasing severity of cognitive syndromes. Clinicians should consider the relevance of neuropsychiatric disorders and symptoms in patients with cognitive disturbances, and incorporate a thorough psychiatric examination in the evaluation of patients.

Genetic Variation in the G720/G30 Gene Locus (DAOA) Influences the Occurrence of Psychotic Symptoms in Patients with Alzheimer's Disease

The occurrence of neuropsychiatric symptoms in patients with Alzheimer's disease hampers the clinical management and exacerbates the burden for caregivers. To what extent psychotic symptoms are genetically determined and which are the genes involved has to be established. We tested the hypothesis that the occurrence of delusions and hallucinations in AD is associated with variations in the G72/DAOA gene, which is supposed to play a key role in the glutamate pathway regulated through the NMDA receptors. A panel of single nucleotide polymorphisms were genotyped in a cohort of 185 Alzheimer's disease patients. The analysis demonstrated a nominally significant association (p< 0.05) with one single nucleotide polymorphism (rs2153674). In addition, multivariate regression showed that the rs2153674 genotype accounts for up to 15% of the variance in delusions severity, as assessed by using the Neuropsychiatric Inventory. If the results from the present study will be replicated, the glutamate hypothesis could be invoked to explain the occurrence of psychosis in neurodegenerative disorders.

Vascular factors and risk for neuropsychiatric symptoms in Alzheimer's disease: the Cache County Study

To examine, in an exploratory analysis, the association between vascular conditions and the occurrence of neuropsychiatric symptoms (NPS) in a population-based sample of incident Alzheimer's disease (AD). The sample consisted of 254 participants, identified through two waves of assessment. NPS were assessed using the Neuropsychiatric Inventory. Prior to the onset of AD, data regarding a history of stroke, hypertension, hyperlipidemia, heart attack or coronary artery bypass graft (CABG), and diabetes were recorded. Logistic regression procedures were used to examine the relationship of each vascular condition to individual neuropsychiatric symptoms. Covariates considered were age, gender, education, APOE genotype, dementia severity, and overall health status. One or more NPS were observed in 51% of participants. Depression was most common (25.8%), followed by apathy (18.6%), and irritability (17.7%). Least common were elation (0.8%), hallucinations (5.6%), and disinhibition (6.0%). Stroke prior to the onset of AD was associated with increased risk of delusions (OR = 4.76, p = 0.02), depression (OR = 3.87, p = 0.03), and apathy (OR = 4.48, p = 0.02). Hypertension was associated with increased risk of delusions (OR = 2.34, p = 0.02), anxiety (OR = 4.10, p = 0.002), and agitation/aggression (OR = 2.82, p = 0.01). No associations were observed between NPS and diabetes, hyperlipidemia, heart attack or CABG, or overall health. Results suggest that a history of stroke and hypertension increase the risk of specific NPS in patients with AD. These conditions may disrupt neural circuitry in brain areas involved in NPS. Findings may provide an avenue for reduction in occurrence of NPS through the treatment or prevention of vascular risk conditions.

Research and Care of Patients With Dementia: Moving Beyond Memory Loss

Received Aug. 26, 2005; accepted Sept. 26, 2005. From the Depts. of Psychiatry, Neurology, and Epidemiology, Univ. of California, San Francisco, and the San Francisco VA Medical Center. Send correspondence and reprint requests to Kristine Yaffe, M.D., Univ. of California, San Francisco, 4150 Clement St., San Francisco, CA 94121. e-mail: kyaffe@itsa.ucsf.edu 2005 American Association for Geriatric Psychiatry Alzheimer disease (AD), the most common cause of dementia, currently affects over 4 million individuals in the United States and has an annual cost of $100 billion. By the year 2050, the number of individuals affected by AD is projected to quadruple. Mild cognitive impairment (MCI), represents a cognitive state between normal cognitive aging and dementia, usually referring to patients with memory impairment. The prevalence of MCI is thought to be even higher than that of dementia, with a recent population-based study reporting that 23% of the elderly population had MCI. In addition to its common occurrence, MCI is a clinically significant condition because many patients with this diagnosis are at an increased risk for dementia, especially dementia of the Alzheimer type. Given the projected demographic shift in our population and the devastating nature of these illnesses, the imperative to study dementia and MCI is even greater. This issue of the Journal, dedicated to dementia, underscores some exciting emerging themes in dementia research: 1) the importance of non–memorydomain impairment, such as frontal lobe or executive functioning in AD and other dementias; 2) the common occurrence of neuropsychiatric symptoms (NPS) of dementia and the need for better treatment of these symptoms; 3) new directions in the treatment of AD and amnesticMCI; 4) ethnic/racial differences on rate of cognitive decline; and 5) how to measure severe dementia and the impact of severe dementia on caregiver decision-making. The Role of Non-Memory CognitiveDomain Impairment in AD