Project description:BackgroundBehavioral and psychological symptoms (BPSD) can be a prodrome of dementia, and the Neuropsychiatric Inventory (NPI) is widely used for BPSD evaluation.ObjectiveTo compare the prevalence of BPSD according to cognitive status, and to determine NPI cutoffs that best discern individuals with mild cognitive impairment (MCI) and dementia from those without dementia.MethodsWe included 1,565 participants (mean age = 72.7±12.2 years, 48% male). BPSD and cognitive status were assessed with the NPI and the Clinical Dementia Rating (CDR). We used multivariable logistic regression models to investigate the association of BPSD with cognitive status. The area under the curve (AUC) was used to assess model discrimination, and to determine the best NPI cutoff for MCI and dementia.ResultsParticipants were cognitively normal (CDR = 0; n = 1,062), MCI (CDR = 0.5; n = 145), or dementia (CDR≥1.0, n = 358). NPI symptoms were more frequent in dementia and MCI when compared to cognitively normal. Higher odds for delusions, hallucinations, disinhibition, and psychomotor alterations were found among participants with dementia and MCI than in those who were cognitively normal. The best NPI cutoff to discern participants with dementia from those cognitively normal was 11 (AUC = 0.755). Poor discrimination (AUC = 0.563) was found for the comparison of MCI and those cognitively normal.ConclusionsWe found an increase in BPSD frequencies across the continuum of cognitive impairment. BPSD severity and frequency in MCI was more similar to individuals cognitively normal than with dementia. NPI scores≥to 11 in individuals with no diagnosis of dementia can support the decision for further investigation of dementia.
Project description:BackgroundSelf-reported discrimination is a source of psychosocial stress that has been previously associated with poor cognitive function in older African Americans without dementia.ObjectiveHere, we examine the association of discrimination with dementia and cognitive impairment in racially diverse older Brazilians.MethodsWe included 899 participants 65 years or older (34.3% Black) from the Pathology, Alzheimer's and Related Dementias Study (PARDoS), a community-based study of aging and dementia. A structured interview with informants of the deceased was conducted. The interview included the Clinical Dementia Rating (CDR) Scale for the diagnosis of dementia and cognitive impairment proximate to death and the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) as a second measure of cognitive impairment. Informant-reported discrimination was assessed using modified items from the Major and Everyday Discrimination Scales.ResultsDiscrimination was reported by informants of 182 (20.2%) decedents and was more likely reported by informants of Blacks than Whites (25.3% versus 17.6%, p = 0.006). Using the CDR, a higher level of informant-reported discrimination was associated with higher odds of dementia (OR: 1.24, 95% CI 1.08 -1.42, p = 0.002) and cognitive impairment (OR: 1.21, 95% CI: 1.06 -1.39, p = 0.004). Similar results were observed using the IQCODE (estimate: 0.07, SE: 0.02, p = 0.003). The effects were independent of race, sex, education, socioeconomic status, major depression, neuroticism, or comorbidities.ConclusionHigher level of informant-reported discrimination was associated with higher odds of dementia and cognitive impairment in racially diverse older Brazilians.
Project description:IntroductionNeuropsychiatric symptoms in dementia (NPS) collectively refer to behavioral and psychological symptoms affecting individuals with mild cognitive impairment (MCI) or Alzheimer's disease or related dementia (ADRD). NPS are among the most troubling aspects of living with dementia and their treatments have limited efficacy. We aim to investigate genetic variants contributing to NPS to identify new therapeutic targets.MethodsWe performed a genome-wide association study (GWAS) for nine NPS domains measured by the NPI-Q in 12,800 participants of European ancestry with MCI or ADRD recruited by Alzheimer's disease research centers across the U.S.ResultsWe found genome-wide significant signals for agitation, anxiety, apathy, delusions, and hallucinations in the APOE locus that were driven by the APOE ε4 allele. We replicated these findings in two independent datasets. Mediation analyses revealed that MCI/ADRD severity only partially mediated the GWAS signals, except for apathy.DiscussionThese findings suggest the APOE ε4 allele influences NPS independently of and beyond its effect on ADRD.
Project description:To examine awareness of memory abilities by groups (healthy control, suspected dementia/mild cognitive impairment, MCI, and diagnosed dementia/MCI), and to describe group differences in the relationship between awareness and cognitive performance in a community sample.In a cross-sectional design, 183 subjects were evaluated in a community setting and categorized into 3 groups based on their cognitive performance and reported medical history. Awareness of memory abilities was quantified using a published anosognosia ratio (AR) comparing the estimated to the objective memory performance by subjects. Each group was further categorized into 'overestimators', 'accurate estimators', and 'underestimators' based on their AR scores.The suspected and diagnosed dementia/MCI groups had significantly higher AR scores than the controls. The suspected group also had a significantly larger proportion (96.2%) of overestimators than the diagnosed (73.3%) and control groups (26.1%). Impaired awareness in overestimators of the suspected and diagnosed groups was correlated with deficits in executive function, language or global cognition.Impaired awareness of memory abilities was prevalent in community-dwelling older adults with suspected and diagnosed dementia or MCI. Those with suspected dementia or MCI were more likely to overestimate their memory abilities than their diagnosed counterparts, suggesting that limited awareness of deficits may hinder utilization of dementia diagnostic services.
Project description:BackgroundNeuropsychiatric symptoms (NPS) are common in mild cognitive impairment (MCI). However, knowledge is limited about the relationship of NPS, clinical factors, and cognition in MCI.MethodsA total of 1099 dementia, 1323 MCI and 377 cognitively normal (CN) were selected from the Tongji Cohort Study of Aging. All participants underwent comprehensive clinical and neuropsychological assessment. NPS were evaluated by the Neuropsychiatric Inventory Questionnaire (NPI-Q). Logistic regression analyses were conducted to investigate the relationship between clinical factors, cognition and NPS.ResultsThe NPS presented in 56.39% of MCI participants, and the NPI-Q scores of MCI was intermediate between CN and dementia. The most common NPS in MCI were depression (30.76%), anxiety (25.09%), apathy (19.43%), and irritability (12.02%). MCI patients with NPS showed worse performance in global, memory, language, and attention than those without NPS. Additionally, Logistic regression analyses revealed that MCI patients with ischemic heart disease (OR = 1.41; 95%CI 1.050-1.897; P = 0.022) were more likely to have NPS, but MCI patients with increased memory domain Z score (OR = 0.847, 95%CI = 0.720-0.996, p = 0.044), and language domain Z score (OR = 0.801, 95%CI = 0.682-0.941, p = 0.007) were less likely to have NPS.ConclusionsNeuropsychiatric symptoms occur commonly in MCI participants, and are mainly related to defect of language and memory function. A better understanding of the relationship between specific cognition and NPS may alert clinicians to pay close attention to the NPS in MCI patient, which may need early intervention.
Project description:Background: The interaction between neuropsychiatric symptoms, mild cognitive impairment (MCI), and dementia is complex and remains to be elucidated. An additive or multiplicative effect of neuropsychiatric symptoms such as apathy or depression on cognitive decline has been suggested. Unraveling these interactions may allow the development of better prevention and treatment strategies. In the absence of available treatments for neurodegeneration, a timely and adequate identification of neuropsychiatric symptom changes in cognitive decline is highly relevant and can help identify treatment targets. Methods: An existing memory clinic-based research database of 476 individuals with MCI and 978 individuals with dementia due to Alzheimer's disease (AD) was reanalyzed. Neuropsychiatric symptoms were assessed in a prospective fashion using a battery of neuropsychiatric assessment scales: Middelheim Frontality Score, Behavioral Pathology in Alzheimer's Disease Rating Scale (Behave-AD), Cohen-Mansfield Agitation Inventory, Cornell Scale for Depression in Dementia (CSDD), and Geriatric Depression Scale (30 items). We subtyped subjects suffering from dementia as mild, moderate, or severe according to their Mini-Mental State Examination (MMSE) score and compared neuropsychiatric scores across these groups. A group of 126 subjects suffering from AD with a significant cerebrovascular component was examined separately as well. We compared the prevalence, nature, and severity of neuropsychiatric symptoms between subgroups of patients with MCI and dementia due to AD in a cross-sectional analysis. Results: Affective and sleep-related symptoms are common in MCI and remain constant in prevalence and severity across dementia groups. Depressive symptoms as assessed by the CSDD further increase in severe dementia. Most other neuropsychiatric symptoms (such as agitation and activity disturbances) progress in parallel with severity of cognitive decline. There are no significant differences in neuropsychiatric symptoms when comparing "pure" AD to AD with a significant vascular component. Conclusion: Neuropsychiatric symptoms such as frontal lobe symptoms, psychosis, agitation, aggression, and activity disturbances increase as dementia progresses. Affective symptoms such as anxiety and depressive symptoms, however, are more frequent in MCI than mild dementia but otherwise remain stable throughout the cognitive spectrum, except for an increase in CSDD score in severe dementia. There is no difference in neuropsychiatric symptoms when comparing mixed dementia (defined here as AD + significant cerebrovascular disease) to pure AD.
Project description:OBJECTIVES:Neuropsychiatric symptoms (NPS) have been recognized to increase the risk of dementia among individuals with mild cognitive impairment (MCI). However, it is unclear whether the risk is shared across the various NPS or driven primarily by selected few symptoms. This study sought to provide confirmatory evidence on the comparative risk of dementia across the various NPS in MCI. DESIGN:Cohort study (median follow-up 4.0 years; interquartile range 2.1-6.4 years). SETTING:Alzheimer's Disease Centers across the United States. PARTICIPANTS:Participants ≥60 years of age and diagnosed with MCI at baseline (n = 8530). MEASURES:Participants completed the Neuropsychiatric Inventory-Questionnaire at baseline and were followed up almost annually for incident dementia. Symptom clusters of NPS, as identified from confirmatory factor analyses, were included in Cox regression to investigate their comparative risks of dementia. RESULTS:Three symptom clusters of NPS were identified among participants with MCI, namely hyperactivity, affective, and psychotic symptoms. The risk of dementia was present among participants with affective symptoms [hazard ratio (HR) 1.6, 95% confidence interval (CI) 1.4-1.9] and psychotic symptoms (HR 1.6, 95% CI 1.2-2.2), but not among those with hyperactivity symptoms (HR 1.1, 95% CI 0.9-1.3). The risk was higher when affective symptoms and psychotic symptoms co-occurred (HR 2.5, 95% CI 2.0-3.2), with one-half of the participants in this group developing dementia within 2.7 years of follow-up. CONCLUSIONS AND IMPLICATIONS:The findings illustrate the potential usefulness of NPS as a convenient prognostic tool in the clinical management of MCI. They also suggest the need for future research to focus on affective/psychotic symptoms in MCI when studying the neurobiological links between NPS and neurodegenerative processes.
Project description:IntroductionCirculating tryptophan (Trp) and its downstream metabolites, the kynurenines, are potentially neuroactive. Consequently, they could be associated with neuropsychiatric symptoms and cognitive prognosis in patients with dementia.ObjectiveThe objective of this study was to assess associations between circulating kynurenines, cognitive prognosis, and neuropsychiatric symptoms.MethodsWe measured baseline serum Trp, neopterin, pyridoxal 5'-phosphate (PLP), and 9 kynurenines in 155 patients with mild dementia (90 with Alzheimer's disease, 65 with Lewy body dementia). The ratios between kynurenine and Trp and kynurenic acid (KA) to kynurenine (KKR) were calculated. The Mini-Mental State Examination (MMSE) and the Neuropsychiatric Inventory (NPI) were administered at baseline and annually over 5 years. Associations between baseline metabolite concentrations with MMSE and the NPI total score were assessed using a generalized structural equation model (mixed-effects multiprocess model), adjusted for age, sex, current smoking, glomerular filtration rate, and PLP. Post hoc associations between KKRs and individual NPI items were assessed using logistic mixed-effects models. False discovery rate (0.05)-adjusted P values (Q values) are reported.ResultsKynurenine had a nonlinear quadratic relationship with the intercept of the MMSE scores over 5 years (Q < 0.05), but not with the slope of MMSE decline. Kynurenine was associated with a higher NPI total score over time (Q < 0.001). Post hoc, both KKR and KA were associated with more hallucinations (Q < 0.05).ConclusionsKynurenine has a complex relationship with cognition, where both low and high levels were associated with poor cognitive performance. A higher KKR indicated risk for neuropsychiatric symptoms, especially hallucinations.