Steinberg, M. et al. Point and 5-year period prevalence of neuropsychiatric symptoms in dementia: the Cache County Study. Int. J. Geriatr. Psychiatry 23, 170-177

Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
International Journal of Geriatric Psychiatry (Impact Factor: 2.87). 02/2008; 23(2):170-7. DOI: 10.1002/gps.1858
Source: PubMed


Neuropsychiatric symptoms are nearly universal in dementia, yet little is known about their longitudinal course in the community.
To estimate point and 5-year period prevalence of neuropsychiatric symptoms in an incident sample of 408 dementia participants from the Cache County Study.
The Neuropsychiatric Inventory assessed symptoms at baseline and at 1.5 years, 3.0 years, 4.1 years, and 5.3 years. Point prevalence, period prevalence and mean symptom severity at each time point were estimated.
Point prevalence for delusions was 18% at baseline and 34-38% during the last three visits; hallucinations, 10% at baseline and 19-24% subsequently; agitation/aggression fluctuated between 13% and 24%; depression 29% at baseline and 41-47% subsequently; apathy increased from 20% at baseline to 51% at 5.3 years; elation never rose above 1%; anxiety 14% at baseline and 24-32% subsequently; disinhibition fluctuated between 2% and 15%; irritability between 17% and 27%; aberrant motor behavior gradually increased from 7% at baseline to 29% at 5.3 years. Point prevalence for any symptom was 56% at baseline and 76-87% subsequently. Five-year period prevalence was greatest for depression (77%), apathy (71%), and anxiety (62%); lowest for elation (6%), and disinhibition (31%). Ninety-seven percent experienced at least one symptom. Symptom severity was consistently highest for apathy.
Participants were most likely to develop depression, apathy, or anxiety, and least likely to develop elation or disinhibition. Give converging evidence that syndromal definitions may more accurately capture neuropsychiatric co-morbidity in dementia, future efforts to validate such syndromes are warranted.

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    • "Depression is consistently reported as one of the most prevalent co-morbidities in AD (Lyketsos and Olin, 2002; Steinberg et al., 2008). Its incidence scales with AD progression (Steinberg et al., 2008), and a diagnosis of major depressive disorder (MDD) predicts a poorer cognitive outcome in later life, with increased risk of developing AD (Ownby et al., 2006). "
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    ABSTRACT: Alzheimer's disease (AD) and major depressive disorder (MDD) are highly prevalent neuropsychiatric conditions with intriguing epidemiological overlaps. Depressed patients are at increased risk of developing late-onset AD, and around one in four AD patients are co-diagnosed with MDD. Microglia are the main cellular effectors of innate immunity in the brain, and their activation is central to neuroinflammation - a ubiquitous process in brain pathology, thought to be a causal factor of both AD and MDD. Microglia serve several physiological functions, including roles in synaptic plasticity and neurogenesis, which may be disrupted in neuroinflammation. Following early work on the 'sickness behavior' of humans and other animals, microglia-derived inflammatory cytokines have been shown to produce depressive-like symptoms when administered exogenously or released in response to infection. MDD patients consistently show increased circulating levels of pro-inflammatory cytokines, and anti-inflammatory drugs show promise for treating depression. Activated microglia are abundant in the AD brain, and concentrate around senile plaques, hallmark lesions composed of aggregated amyloid-β peptide (Aβ). The Aβ burden in affected brains is regulated largely by microglial clearance, and the complex activation state of microglia may be crucial for AD progression. Intriguingly, recent reports have linked soluble Aβ oligomers, toxins that accumulate in AD brains and are thought to cause memory impairment, to increased brain cytokine production and depressive-like behavior in mice. Here, we review recent findings supporting the inflammatory hypotheses of AD and MDD, focusing on microglia as a common player and therapeutic target linking these devastating disorders.
    Full-text · Article · Nov 2015 · Brain Behavior and Immunity
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    • "Although Alzheimer's Disease (AD) is the most common form of dementia, 25% of patients have vascular dementia (VaD) and a further 20–40% have mixed dementia with VaD and AD. More than 90% of patients with dementia will experience at least one behavioural and psychological symptoms of dementia (BPSD), such as delusions, hallucinations, agitation and aggression, during the course of their condition (Steinberg et al., 2008). These symptoms are frequently extremely distressing to patients, stressful to carers and present a significant clinical challenge for treatment. "
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    ABSTRACT: Objectives People with vascular dementia (VaD) are frequently prescribed atypical antipsychotics to treat behavioural and psychological symptoms, but there is an alarming lack of evidence regarding their safety or efficacy in VaD. This study sought to identify the mortality risk associated with the most commonly prescribed atypical antipsychotics in people with VaD compared with people not exposed to these drugs.MethodsA clinical cohort study of 1531 people with VaD performed using anonymised versions of full electronic health records from the Clinical Record Interactive Search application at the South London and Maudsley NHS Foundation Trust. Patients were identified from 2007 to 2010, of whom 337 were exposed to quetiapine, risperidone or olanzapine. The main outcome measure was mortality.ResultsPatients exposed to atypical antipsychotics were not at increased risk of mortality [hazard ratio (HR) 1.05, 95% confidence interval (CI): 0.87–1.26]. Exposure to risperidone did not result in an increased risk of mortality (HR = 0.85; 95% CI: 0.59–1.24), and patients exposed to quetiapine had a non-significant numerical increase in mortality risk (HR = 1.14; 95% CI: 0.93–1.39; p-value = 0.20) compared with untreated patients. Too few patients were exposed to olanzapine alone to provide reliable results.Conclusions The absence of a significant increase in mortality risk associated with atypical antipsychotics in people with VaD indicates that a clinical trial of antipsychotics focussing on the treatment of aggression and agitation in this patient group will be justified and feasible following further consideration of possible confounders, which will be critical to determine the role of antipsychotics in treatment of VaD. Copyright © 2014 John Wiley & Sons, Ltd.
    Full-text · Article · Dec 2014 · International Journal of Geriatric Psychiatry
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    • "Depressive symptoms in mild cognitive impairment subjects have also been linked to further progression to dementia (Gabryelewicz et al., 2007), and an increased brain atrophy over a period of 2 years (Lee et al., 2012), suggesting that depression in general may be a risk factor for developing AD (Ownby et al., 2006). Agitation and aggression have been reported to range from 48% to 80% in AD patients (Tractenberg et al., 2002) with symptoms remaining persistent over months and occurring across all AD stages (Steinberg et al., 2008). Neurochemical studies that assessed postmortem brain levels of different monoamines and metabolites associated with specific NPS features are very limited and date from over 2 decades ago (Palmer et al., 1988; Zubenko et al., 1990). "
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    ABSTRACT: Background: Depression and aggression in Alzheimer’s disease (AD) are two of the most severe and prominent neuropsychiatric symptoms (NPS). Altered monoaminergic neurotransmitter system functioning has been implicated in both NPS, although their neurochemical etiology remains to be elucidated. Methods: Left frozen hemispheres of 40 neuropathologically confirmed AD patients were regionally dissected. Dichotomization based on depression/aggression scores resulted in depressed/nondepressed (AD+D/-D) and aggressive/nonaggressive (AD+Agr/-Agr) groups. Concentrations of dopamine, serotonin (5-HT), (nor)epinephrine ((N)E) and respective metabolites were determined using RP-HPLC. Results: Significantly lower 3-methoxy-4-hydroxyphenylglycol (MHPG) and higher homovanillic acid levels were observed in Brodmann area (BA) 9 and 10 of AD+D compared to AD-D. In AD+Agr, 5-hydroxy-3-indoleacetic acid (5-HIAA) levels in BA9, 5-HIAA/5-HT ratios in BA11, and MHPG, NE, and 5-HIAA levels in hippocampus were significantly decreased compared to AD-Agr. Conclusions: These findings indicate that brain region-specific altered monoamines and metabolites may contribute to the occurrence of depression and aggression in AD.
    Full-text · Article · May 2014 · Neurobiology of Aging
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