Neuropsychiatric Symptoms In Mild Cognitive Impairment Research Articles

Neuropsychiatric and cognitive features of major depressive disorder in aging, based on the data from the US National Alzheimer's Coordinating Center (NACC)

ObjectiveThe diagnosis of Major Depressive Disorder (MDD) is based on the DSM-V criteria and is established by a clinician. This allows quantifying depression based on clinical criteria. As such, MDD differs from other types of depressions that are measured by subjective scales. Here, we evaluated the MDD risk factor on other neuropsychiatric symptoms (NPS) as well as MDD association with cognitive performance in Alzheimer's disease (AD), Mild Cognitive Impairment (MCI) and Healthy Controls (HC). MethodsData of 208 patients with AD, 291 patients with MCI and 647 HC were extracted from the National Alzheimer's Coordinating Center database. All participants included in this study were assessed by a physician for the MDD criteria, underwent an NPS evaluation using the NeuroPsychiatric Inventory, and a comprehensive cognitive assessment. Participants were classified as being with and without MDD. We performed logistic regression and MANCOVA models respectively with NPS and cognitive performance as variables of interest and MDD as fixed factors within each group. The MANCOVA was controlled for the effects of age, sex, and education. ResultsMDD increased the risk for psychotic, affective and behavioral NPS in MCI, as well as affective and behavioral NPS in HC and AD. Also, MCI with MDD had lower performance on selective attention and mental flexibility. ConclusionsMDD seems to increase the probability of a prevalence of NPS in all groups (HC, MCI and AD). Longitudinal data processing would help to understand the neuropsychiatric evolution of elderly subjects with MDD.

Neuropsychiatric symptoms influence differently cognitive decline in older women and men

ObjectiveThe potential impact of sex on cognitive performance in normal aging and participants with Alzheimer's disease (AD) has been outlined previously. Nevertheless, differences in neuropsychiatric symptoms (NPS) have been also outlined. We aimed to study a potential association between NPS and cognitive performances according to sex, in older individuals with and without cognitive impairment. MethodsDemographic, neuropsychiatric and neuropsychological data from the ADNI and NACC databases were merged into a dataset of 506 participants with healthy cognitive performance, 467 patients with mild cognitive impairment, and 238 patients with AD. Cognitive performance in each group was evaluated according to sex and the presence of NPS. ResultsBased on sex, cognitive performance differed according to clinical stage: in the healthy controls and AD groups, women had better fluency performance, while in the mild cognitive impairment group, women had better working memory and men better oral naming. Regardless of sex, depression showed a negative effect on processing speed in AD. Finally, there was an interaction between sex and NPS in mild cognitive impairment, where women with apathy had better working memory performance, and in AD, women with depression had better fluency performance. The opposite pattern being was observed in men, where men with depression have worse focused attention. ConclusionCognitive performance is influenced by sex, yet this influence has different manifestations at normal cognition, MCI or AD. Furthermore, apathy and depression seem to influence differently women and men at different types of cognitive decline.

Non-Pharmacological Treatments of Neuropsychiatric Symptoms in Mild Cognitive Impairment.

Mild cognitive impairment (MCI) is a syndrome defined by objective cognitive deficits that do not impact functional independence. Individuals with MCI develop dementia at an annual rate of 10 to 15%. Neuropsychiatric symptoms (NPS) are common non-cognitive features of neurocognitive disorders and have a major impact on the wellbeing and quality of life of affected individuals and their families. Non-pharmacological interventions for NPS are considered the first-line treatment because of the limited efficacy and side-effect potential of current pharmacological agents. This article summarizes the literature on non-pharmacological treatments for NPS in MCI. The limited number of studies specific to individuals with MCI and its various etiologies, as well as the overall heterogeneity of research design and methodologies, make the evidence base inconclusive. Nevertheless, some studies support psychosocial interventions aimed at individuals with MCI and their caregivers.

Neuropsychiatric symptoms and brain morphology in patients with mild cognitive impairment and Alzheimer's disease with dementia.

Neuropsychiatric symptoms (NPS) are common in mild cognitive impairment (MCI) and Alzheimer’s disease with dementia (AD dementia), but their brain structural correlates are unknown. We tested for associations between NPS and MRI-based cortical and subcortical morphometry in patients with MCI and AD dementia. Cross-sectional. Conducted in Norway. Patients with MCI (n = 102) and AD dementia (n = 133) from the Memory Clinic and the Geriatric Psychiatry Unit at Oslo University Hospital. Neuropsychiatric Inventory – Questionnaire (NPI-Q) severity indices were reduced using principal component analysis (PCA) and tested for associations with 170 MRI features using linear models and false discovery rate (FDR) adjustment. We also tested for differences between groups. For transparency, we added analyses with selected NPI-Q items. PCA revealed four factors: elation, psychosis, depression, and motor behavior.FDR adjustment revealed a significant positive association (B = 0.20, pFDR < 0.005) between elation and thickness of the right caudal anterior cingulate cortex (ACC) across groups, and significant interactions between diagnosis and psychosis (B=−0.48, pFDR < 0.0010) on the left post-central volume and between diagnosis and depression (B=−0.40, pFDR < 0.005) on the thickness of the banks of the left superior temporal sulcus. Associations of apathy, anxiety, and nighttime behavior to the left temporal lobe were replicated. The positive association between elation and ACC thickness suggests that mechanisms other than atrophy underly elation. Interactions between diagnosis and NPS on MRI features suggest different mechanisms of NPS in our MCI and AD dementia samples. The results contribute to a better understanding of NPS brain mechanisms in MCI and AD dementia.

Novel neurostimulation approaches: Focus on neuropsychiatric symptoms

Neuropsychiatric symptoms (NPS) such as depression, apathy and agitation are common in neurocognitive disorders such as Alzheimer's disease (AD) and its prodrome, Mild Cognitive Impairment (MCI). Importantly, the presence of NPS is a prognostic indicator of future decline in MCI and AD and reduces quality of life in both patients and caregivers. Pharmacological interventions for NPS in neurocognitive disorders have not been shown to be effective and moreover, often have unfavourable side effect profiles for older adults due to age-related changes in pharmacokinetics and pharmacodynamics and the presence of comorbid medical conditions. Non-pharmacological approaches such as neurostimulation are increasingly being applied to treat primary psychiatric and neuropsychiatric conditions and hold promise for treatment of NPS in neurocognitive conditions, both from a symptom management point of view, and as a potential disease-modifying intervention for neurocognitive disorders. In this session, we will review novel neurostimulation modalities including transcranial direct current stimulation (tDCS), deep transcranial magnetic stimulation (dTMS), and photobiomodulation and their application to treatment of NPS in MCI and AD. Preliminary findings will be reviewed from ongoing clinical trials of neurostimulation for NPS in neurocognitive disorders: 1) Transcranial direct current stimulation (tDCS) combined with exercise for treatment of apathy in AD (Dr. Krista Lanctôt); 2) TDCS for treatment of agitation in AD (Dr. Sanjeev Kumar); 3) Deep transcranial magnetic stimulation (dTMS) for depression in MCI or AD [ClinicalTrials.gov Identifier: NCT03665831] (Dr. Linda Mah); 4) Photobiomodulation therapy for AD and as a potential treatment for NPS in neurocognitive disorders (Dr. Corinne Fischer).

Affective symptoms and regional cerebral tau burden in early‐stage Alzheimer's disease

Neuropsychiatric symptoms (NPS) are often present in individuals with mild cognitive impairment (MCI) and Alzheimer's disease (AD) dementia. NPS are associated with structural and functional changes in the brain such as atrophy, regional hypometabolism, and hypoperfusion, considered proxies of neurodegeneration. Our objective was to evaluate the association between NPS and regional cerebral tau burden, a more direct representation of neurodegeneration, in cognitively normal (CN), MCI, and AD dementia individuals. Cross-sectional NPS were assessed using the Neuropsychiatric Inventory (NPI) in 410 CN, 199 MCI, and 61 AD dementia participants who underwent flortaucipir tau positron emission tomography as part of the AD Neuroimaging Initiative (ADNI). Total NPI score and two factors of NPS (affective and hyperactive) were used in analyses. Linear regression models with backward elimination were employed with NPI as dependent variable and regional tau or tau-amyloid interaction as predictor of interest. Covariates included education, age, sex, Rey Auditory Verbal Learning Test Total Learning, and Trail Making TestB. There were significant associations (p<0.05) between the NPI variables (total score, Affective factor) and entorhinal and precuneus tau across all participants. These associations were also significant for the tau-amyloid interaction. These effects were significant in cognitively symptomatic participants (MCI and AD dementia), but not in CN participants. Increased tau burden in the entorhinal and precuneus cortices was modestly associated with greater NPS in MCI and AD dementia. Further evaluation of NPS and their effect on early-stage AD could aid in finding new interventions and slowing disease progression.

NOVEL NEUROSTIMULATION APPROACHES: FOCUS ON NEUROPSYCHIATRIC SYMPTOMS

Neuropsychiatric symptoms (NPS) such as depression, apathy and agitation are common in neurocognitive disorders such as Alzheimer's disease (AD) and its prodrome, Mild Cognitive Impairment (MCI). Importantly, the presence of NPS is a prognostic indicator of future decline in MCI and AD and reduces quality of life in both patients and caregivers. Pharmacological interventions for NPS in neurocognitive disorders have not been shown to be effective and moreover, often have unfavourable side effect profiles for older adults due to age-related changes in pharmacokinetics and pharmacodynamics and the presence of comorbid medical conditions. Non-pharmacological approaches such as neurostimulation are increasingly being applied to treat primary psychiatric and neuropsychiatric conditions and hold promise for treatment of NPS in neurocognitive conditions, both from a symptom management point of view, and as a potential disease-modifying intervention for neurocognitive disorders. In this session, we will review novel neurostimulation modalities including transcranial direct current stimulation (tDCS), deep transcranial magnetic stimulation (dTMS), and photobiomodulation and their application to treatment of NPS in MCI and AD. Preliminary findings will be reviewed from ongoing clinical trials of neurostimulation for NPS in neurocognitive disorders: 1) Transcranial direct current stimulation (tDCS) combined with exercise for treatment of apathy in AD (Dr. Krista Lanctôt); 2) TDCS for treatment of agitation in AD (Dr. Sanjeev Kumar); 3) Deep transcranial magnetic stimulation (dTMS) for depression in MCI or AD [ClinicalTrials.gov Identifier: NCT03665831] (Dr. Linda Mah); 4) Photobiomodulation therapy for AD and as a potential treatment for NPS in neurocognitive disorders (Dr. Corinne Fischer).

Assessing Mild Behavioral Impairment with the Mild Behavioral Impairment-Checklist in People with Mild Cognitive Impairment.

Neuropsychiatric symptoms (NPS) are non-cognitive, behavioral, or psychiatric symptoms, common in mild cognitive impairment (MCI) and associated with a higher risk of dementia. Mild behavioral impairment (MBI) is a validated diagnostic entity, that describes the emergence of later life NPS in pre-dementia states. The Mild Behavioral Impairment Checklist (MBI-C) is the first measure developed to assess MBI. To estimate the prevalence of MBI in people with MCI and to study the score distribution, sensitivity, specificity, diagnostic utility of the MBI-C, and its correlations with neuropsychological tests. One hundred eleven MCI participants were evaluated with the Questionnaire for Subjective Memory Complaints (QSMC), Mini-Mental State Examination, Cambridge Cognitive Assessment-Revised, Neuropsychiatric Inventory-Questionnaire (NPI-Q), Geriatric Depression Scale-15 items (GDS-15), Lawton and Brody Index, and the MBI-C, which was administered by phone to participants' informants. Descriptive, logistic regression, ROC curve, and bivariate correlations analyses were performed. MBI diagnosis prevalence was 14.2%. The total MBI-C score differentiated people with MBI at a cutoff-point of 6.5, optimizing sensitivity and specificity. MBI-C total score correlated positively with NPI-Q, QSMC, GDS-15, and Lawton and Brody Index. The total MBI-C score, obtained by phone administration, is sensitive for detecting MBI in people with MCI. The MBI-C scores indicated that MCI participants had subtle NPS that were correlated to their subjective memory complaints reported by informants, depressive symptoms, and negatively with Instrumental Activities of Daily Living. Further research should be done to clarify the predictive role of NPS in MCI for incident dementia.

Frequency and subgroups of neuropsychiatric symptoms in mild cognitive impairment and different stages of dementia in Alzheimer's disease.

Neuropsychiatric symptoms (NPS), such as depression, apathy, agitation, and psychotic symptoms are common in mild cognitive impairment (MCI) and dementia in Alzheimer's disease (AD). Subgroups of NPS have been reported. Yet the relationship of NPS and their subgroups to different stages of cognitive impairment is unclear. Most previous studies are based on small sample sizes and show conflicting results. We sought to examine the frequency of NPS and their subgroups in MCI and different stages of dementia in AD. This was a cross-sectional study using data from a Norwegian national registry of memory clinics. From a total sample of 4,571 patients, we included those with MCI or AD (MCI 817, mild AD 883, moderate-severe AD 441). To compare variables across groups ANOVA or χ 2-test was applied. We used factor analysis of Neuropsychiatric Inventory Questionnaire (NPI-Q) items to identify subgroups of NPS. The frequency of any NPS was 87.2% (AD 91.2%, MCI 79.5%; p < 0.001) and increased with increasing severity of cognitive decline. The most frequent NPS in MCI was depression. Apathy was the most frequent NPS in AD across different stages of severity. The factor analysis identified three subgroups in MCI and mild AD, and a fourth one in moderate-severe AD. We labelled the subgroups "depression," "agitation," "psychosis," and "elation." The frequency of NPS is high in MCI and AD and increases with the severity of cognitive decline. The subgroups of NPS were relatively consistent from MCI to moderate-severe AD. The subgroup elation appeared only in moderate-severe AD.

Development and Testing of a Neuropsychiatric Symptoms Model in Mild Cognitive Impairment.

Neuropsychiatric symptoms are prevalent in individuals with mild cognitive impairment (MCI) and have a significant detrimental effect on health and quality of life. Identifying factors that contribute to their occurrence may enable prompt treatment and intervention. The current study entails the development and testing of a biopsychosocially based model to assist nurses in the identification of individuals with MCI who are most likely to experience symptoms of depression, apathy, and/or anxiety. Factors within the biological and sociodemographic domains of the Neuropsychiatric Symptoms in MCI (NPSMCI) model were tested using multivariate logistic regression analyses. Findings suggest that age, presence of an e4 allele of the apolipoprotein E gene, living situation, and degree of comorbid illness were associated with the occurrence of symptoms of depression and apathy. Further testing and refinement are necessary, but the findings provide guidance to nurses and alert them to assess individuals most likely to experience these symptoms. [Journal of Gerontological Nursing, 44(1), 21-30.].

THE PREVALENCE OF NEUROPSYCHIATRIC SYMPTOMS IN MILD COGNITIVE IMPAIRMENT: A COMPARISON BETWEEN TAIWAN AND WESTERN STUDIES

Neuropsychiatric symptoms (NPS) may be prevalent in patients with mild cognitive impairment (MCI). However, little studies compare NPS of MCI between Taiwanese and Western samples. This was a cross-sectional study. A total of 268 participants were recruited from the outpatient clinics of two hospitals in Northern Taiwan from 2007–2011. A total of 249 participants completed the cognitive and neuropsychiatric evaluations, including 90 normal controls (NC) and 159 MCI subjects. The MCI criteria followed Petersen criteria except with more stringent requirement that the neurocognitive impairment had to be 4% below mean of norm. The Neuropsychiatric Inventory (NPI) was used to assess the NPS. The prevalence of each neuropsychiatric symptoms was compared between our study and previous studies. The prevalence of at least one NPS in MCI group was 54.7%. Four of the most prevalent neuropsychiatric symptoms in MCI were night-time behavior disturbances (22.0%), apathy (20.1%), irritability (16.4%) and depression (14.5%). When compared with Western studies (including clinical MCI and population-based MCI samples), the prevalence of NPS in our clinical sample was more similar to that of population-based samples, but less than that of clinical sample from Western countries. Our findings suggest the prevalence of NPS in Taiwanese clinical MCI sample is more similar to that of population-based samples, rather than clinical samples, in Western studies. It could be related to easy accessibility to hospitals in Taiwan. Our results are also consistent with previous epidemiological studies in Taiwan showing lower prevalence of depression and anxiety by non-physician interviewers when compared with Western studies.

Neuropsychiatric symptoms in South-East Asian patients with mild cognitive impairment and dementia: prevalence, subtypes, and risk factors.

The subtypes and risk factors of neuropsychiatric symptoms remain largely unexplored in South-East Asian populations. We investigated the prevalence, subtypes, and risk factors, namely, demographic, medical morbidity, and cognitive impairment associated with neuropsychiatric symptoms in a South-East Asian cohort of patients with mild cognitive impairment (MCI) and dementia. A clinical cohort of 38 MCI and 198 mild-moderate dementia patients were assessed using the Neuropsychiatric Inventory-Questionnaire. Neuropsychiatric symptoms were equally prevalent among patients with MCI (74%) and mild-moderate dementia (85%). Three subtypes of symptoms were identified for each diagnostic group; for MCI, they included mood disturbances, anxiety/sleep problems, and psychosis, while for dementia, the subtypes included behavioral disturbances, psychosis/mood, and hyperactive behaviors. The largest risk for neuropsychiatric symptoms for both MCI and dementia patients was male gender. Among patients with MCI, burden of cerebrovascular disease and global cognitive impairment were small risks for neuropsychiatric symptoms, while for patients with dementia, an older age (>65years) was a small risk and lower educational attainment was a moderate risk. These findings contribute to the worldwide epidemiology of neuropsychiatric symptoms in MCI and dementia and highlight that the profile of symptoms, subtypes, and risks is fairly homogenous across Western and Asian cultures. Copyright © 2017 John Wiley & Sons, Ltd.

Mild behavioral impairment (MBI): Background, description of the construct, and criteria development

Neuropsychiatric Symptoms (NPS) are common in dementia and pre-dementia syndromes such as Mild Cognitive Impairment (MCI). NPS in MCI confer a greater risk for conversion to dementia in comparison to MCI patients without NPS. Mild Behavioral Impairment (MBI) has been proposed as a diagnostic construct aimed to identify patients with an increased risk of developing dementia, but who may or may not have manifested cognitive symptoms. Initial discussion around the need for new MBI criteria stemmed from the annual meeting of the NPS Professional Interest Area (PIA) of the International Society to Advance Alzheimer's Research and Treatment (ISTAART) at the Alzheimer's Association International Conference (AAIC) 2012 in Vancouver, Canada. Conference proceedings and papers, Pubmed and Medline searches were performed with search criteria “mild behavioral impairment”, “MBI”, “prodromal dementia”, “neuropsychiatric symptoms of dementia”, “non-cognitive symptoms of dementia”, “NPS”, “behavioral and psychological symptoms of dementia” and “BPSD”. Both the American and United Kingdom spelling of “behavior/behaviour” were used in the search. Full text articles of relevant abstracts were reviewed, as were reference lists and citations. Authors ZI and CGL modified existing Taragano criteria, the Mendonca FTD-MCI criteria, and the NIA-AA Alzheimer's Disease criteria to incorporate current nomenclature and research. These criteria were then presented to the NPS-PIA at AAIC 2013 in Boston, Massachusetts. The criteria were then modified over the next year via in an iterative process by NPS PIA members. The final criteria then distributed to NPS PIA membership for approval and then subsequently to ISTAART for final approval prior to submission. We present the new proposed research diagnostic criteria for MBI. See Table. The MBI construct is a potential framework for detecting earlier, incipient neurodegenerative illness. The criteria extend previous research in this area and incorporate MCI into the framework. They will facilitate research into understanding NPS as a very early consequence of neurodegenerative disease in some cases, exploring targets for treatment and studying mechanisms of illness progression. The criteria will be subject to studies of reliability, concurrent validity, predictive validity and the development of biomarkers, ultimately leading to therapeutics.

Neuropsychiatric symptoms as early manifestations of emergent dementia: Provisional diagnostic criteria for mild behavioral impairment

Neuropsychiatric symptoms (NPS) are common in dementia and in predementia syndromes such as mild cognitive impairment (MCI). NPS in MCI confer a greater risk for conversion to dementia in comparison to MCI patients without NPS. NPS in older adults with normal cognition also confers a greater risk of cognitive decline in comparison to older adults without NPS. Mild behavioral impairment (MBI) has been proposed as a diagnostic construct aimed to identify patients with an increased risk of developing dementia, but who may or may not have cognitive symptoms. We propose criteria that include MCI in the MBI framework, in contrast to prior definitions of MBI. Although MBI and MCI can co-occur, we suggest that they are different and that both portend a higher risk of dementia. These MBI criteria extend the previous literature in this area and will serve as a template for validation of the MBI construct from epidemiologic, neurobiological, treatment, and prevention perspectives.

The Association of Neuropsychiatric Symptoms in MCI with Incident Dementia and Alzheimer Disease

Individuals with mild cognitive impairment (MCI) are at high risk of developing dementia and/or Alzheimer disease (AD). Among persons with MCI, depression and anxiety have been associated with an increased risk of incident dementia. We examined whether neuropsychiatric symptoms in MCI increased the risk of incident dementia (all-cause) and incident AD. Longitudinal cohort study followed annually (median: 1.58 years). National Alzheimer's Coordinating Center database combining clinical data from 29 Alzheimer's Disease Centers. A total of 1,821 participants with MCI. 1) Progression to dementia (all-cause) or AD, 2) Neuropsychiatric Inventory Questionnaire (NPI-Q), 3) Geriatric Depression Scale (GDS), 4) Clinical Dementia Rating Global Score and Sum of Boxes, and 5) Mini-Mental State Examination (MMSE). The association of covariates with risk of incident dementia or AD was evaluated with hazard ratios (HR) determined by Cox proportional-hazards models adjusted for age, ethnicity, Clinical Dementia Rating Global Score and Sum of Boxes, and MMSE. A total of 527 participants (28.9%) progressed to dementia and 454 (24.9%) to AD. Baseline GDS > 0 was associated with an increased risk of incident dementia (HR: 1.47, 95% CI: 1.17-1.84) and AD (HR: 1.45, 95% CI: 1.14-1.83). Baseline NPI > 0 was associated with an increased risk of incident dementia (HR: 1.37, 95% CI: 1.12-1.66) and AD (HR: 1.35, 95% CI: 1.09-1.66). Neuropsychiatric symptoms in MCI are associated with significantly an increased risk of incident dementia and AD. Neuropsychiatric symptoms may be among the earliest symptoms of preclinical stages of AD and targeting them therapeutically might delay transition to dementia.

Persistence of neuropsychiatric symptoms over six months in mild cognitive impairment in community-dwelling Korean elderly

Several studies of patients with mild cognitive impairment (MCI) have revealed that this population, like people with dementia, have neuropsychiatric symptoms (NPS) as well as memory impairment. No study has reported on the natural history and course of NPS in MCI although this is important in terms of management. We aimed to determine the persistence of NPS over six months in participants with MCI. The Neuropsychiatric Inventory (NPI) was used to rate the severity of NPS in 241 consecutive referrals with MCI from a Korean clinic at baseline and in 220 patients at 6-month follow-up. We also collected information about the cognition and quality of life of patients and their caregivers. Ninety-seven (44.1%) MCI participants who completed the 6-month follow-up exhibited at least one NPS at baseline; 60 (27.3%) were clinically significant NPS. Seventy (72.1%) of those with any symptom had at least one persistent NPS at 6-month follow-up, and 44 (73.3%) of those with clinically significant symptoms had at least one significant and persistent NPS at 6-month follow-up. Those with persistent symptoms had more severe baseline symptoms. Both patients and caregivers had a poorer quality of life when the patient had at least one clinically significant symptom. NPS were highly persistent overall in older people with MCI. Persistence was predicted by having more severe symptoms at baseline. Clinically significant levels of NPS were associated with decreased quality of life. We conclude that clinicians should be aware that NPS symptoms in MCI usually persist.

Neuropsychiatric symptoms in MCI subtypes: the importance of executive dysfunction

Mild cognitive impairment (MCI) is a syndrome thought to be a prodrome of dementia for some patients. One subtype, amnestic MCI (aMCI), may be specifically predispose patients to develop Alzheimer's dementia (AD). Since dementia has been associated with a range of neuropsychiatric symptoms (NPS), we sought to examine the prevalence of NPS in MCI and its subtypes. One thousand seven hundred seventy-nine participants in the National Alzheimer's Coordinating Center (NACC) with MCI were included in this study. All participants were evaluated systematically with a thorough cognitive battery, clinical interview, and consensus diagnoses, and subtyped as: (1) amnestic (aMCI) (single- or multiple-domain) versus non-amnestic (non-aMCI); (2) executive dysfunction-MCI (exMCI) (single- or multiple-domain) versus no executive dysfunction-MCI (non-exMCI); (3) both aMCI and exMCI; and (4) neither aMCI nor exMCI. Additionally, aMCI versus non-aMCI and exMCI versus non-exMCI dichotomies were explored. NPS were assessed with the Neuropsychiatric Inventory Questionnaire (NPI-Q) and Geriatric Depression Scale (GDS). 1379 participants (77.5%) met criteria for aMCI and 616 (34.6%) for exMCI. No differences were observed in the prevalence of NPS between aMCI versus non-aMCI. However, exMCI was associated with greater severity of depression, anxiety, agitation, disinhibition, irritability, and sleep problems, although these differences do not persist after adjustment for multiple comparisons. While there were few associations between aMCI and NPS, the presence of executive dysfunction in MCI was associated with greater severity of symptoms and specifically with depression (evidenced by GDS score) and anxiety. These findings may have implications for MCI prognosis and need to be explored in longitudinal studies.

Neuropsychiatric symptom profiles in Mild Cognitive Impairment and Alzheimer's disease

Mild cognitive impairment (MCI) is a risk state for Alzheimer's disease (AD). It has been well established that behavioral symptoms are commonly observed in AD. Our objective was to determine if the profile of neuropsychiatric symptoms in MCI was qualitatively unique to the profile found in AD. The data were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI), a longitudinal study on healthy aging, MCI, and AD. These analyses included 393 individuals with MCI and 191 individuals with AD who all completed the Neuropsychiatric Inventory Questionnaire (NPI-Q), an informant-based rating scale for assessing the presence and severity of 12 behavioral symptoms. For the MCI and AD groups, factor analyses were conducted on the NPI-Q data. Factors were selected based on the number of eigenvalues > 1, and factor loadings > .40 were considered significant. For the MCI group, ‘mood’ (depression and anxiety) and ‘frontal’ (agitation, disinhibition, and irritability) factors emerged. The analysis for the AD group yielded ‘frontal-behavioral’ (elation and disinhibition), ‘frontal-emotional’ (agitation, apathy, irritability), and ‘psychosis’ (delusions and hallucinations) factors. Our findings indicate that although the two groups share some similar frontal symptoms, mood problems are more common in MCI, while psychotic symptoms are more common in AD. Furthermore, a wider range of frontal symptoms is found in AD. Overall, the behavioral patterns in these groups are qualitatively dissimilar.

A Systematic Review of Neuropsychiatric Symptoms in Mild Cognitive Impairment

Mild cognitive impairment (MCI) is a clinical concept proposed as an intermediate state between normal aging and dementia. This condition has multiple heterogeneous sources, including clinical presentation, etiology, and prognosis. Recently, the prevalence and associated features of neuropsychiatric symptoms (NPS) in MCI have been described. We systematically searched the PubMed database (last accessed on August 31, 2008) for articles on NPS in MCI. Included articles used strict selection criteria, and outcome variables were extracted in duplicate; of the 27 articles included, 14 (52%) used prospective cohorts. The global prevalence of NPS in MCI ranged from 35% to 85%. The most common behavioral symptoms were depression, anxiety, and irritability. Hospital-based samples reported a higher global prevalence of NPS than population-based studies; this discrepancy probably reflected differences in demographics, study setting, MCI diagnostic criteria, and behavioral instruments used. Prospective studies showed that NPS, particularly depression, may represent risk factors for MCI or predictors for the conversion of MCI to Alzheimer's disease (AD). NPS are very prevalent in subjects with MCI, displaying a similar pattern of symptoms compared to dementia and AD. Large cohort studies using standardized MCI criteria and behavioral instruments are required to evaluate the prognostic role of NPS in MCI.

Prevalence of Neuropsychiatric Symptoms in Mild Cognitive Impairment and Normal Cognitive Aging

Little is known about the population-based prevalence of neuropsychiatric symptoms in mild cognitive impairment (MCI). To estimate the prevalence of neuropsychiatric symptoms in MCI and normal cognitive aging in a defined population. Cross-sectional study derived from an ongoing population-based prospective cohort study. The Mayo Clinic Study of Aging. We studied a random sample of 1969 individuals without dementia from the target population of 9965 elderly persons residing in Olmsted County (Minnesota) on the prevalence date (October 1, 2004). Neuropsychiatric data were available for 319 of 329 subjects with MCI (97.0%) and 1590 of 1640 subjects with normal cognition (97.0%). Neurologic, cognitive, and neuropsychiatric data were obtained from the study participants. A classification of MCI, dementia, and normal cognitive aging was adjudicated by an expert consensus panel. Accordingly, 329 subjects were classified as having MCI and the remaining 1640 subjects were classified as having normal cognition. Neuropsychiatric Inventory Questionnaire score. Multivariate logistic regression analyses were conducted after adjusting for age, sex, and educational status. By considering both the odds ratio (OR) and the frequency of a symptom, the most distinguishing features between the 2 groups were apathy (OR, 4.53; 95% confidence interval [CI], 3.11-6.60; P < .001), agitation (3.60; 2.18-5.92; P < .001), anxiety (3.00; 2.01-4.48; P < .001), irritability 2.99; 2.11-4.22; P < .001), and depression (2.78; 2.06-3.76; P < .001). The OR was highest for delusion (8.12; 95% CI, 2.92-22.60; P < .001); however, it was rare in both subjects with MCI (11 of 319 [3.4%]) and those with normal cognition (6 of 1590 [0.4%]). Thus, the population attributable risk for delusion was only 2.62% compared with 14.60% for apathy. Nonpsychotic symptoms affected approximately 50% of subjects with MCI and 25% of subjects with normal cognition. In contrast, psychotic symptoms were rare.