OBJECTIVE: Neuropsychiatric symptoms (NPS) increase risk of developing dementia and are linked to various neurodegenerative conditions, including mild cognitive impairment (MCI due to Alzheimer\'s disease [AD]), cerebrovascular disease (CVD), and Parkinson\'s disease (PD). We explored the structural neural correlates of NPS cross-sectionally and longitudinally across various neurodegenerative diagnoses.
METHODS: The study included individuals with MCI due to AD, (n = 74), CVD (n = 143), and PD (n = 137) at baseline, and at 2-years follow-up (MCI due to AD, n = 37, CVD n = 103, and PD n = 84). We assessed the severity of NPS using the Neuropsychiatric Inventory Questionnaire. For brain structure we included cortical thickness and subcortical volume of predefined regions of interest associated with corticolimbic and frontal-executive circuits.
RESULTS: Cross-sectional analysis revealed significant negative correlations between appetite with both circuits in the MCI and CVD groups, while apathy was associated with these circuits in both the MCI and PD groups. Longitudinally, changes in apathy scores in the MCI group were negatively linked to the changes of the frontal-executive circuit. In the CVD group, changes in agitation and nighttime behavior were negatively associated with the corticolimbic and frontal-executive circuits, respectively. In the PD group, changes in disinhibition and apathy were positively associated with the corticolimbic and frontal-executive circuits, respectively.
CONCLUSIONS: The observed correlations suggest that underlying pathological changes in the brain may contribute to alterations in neural activity associated with MBI. Notably, the difference between cross-sectional and longitudinal results indicates the necessity of conducting longitudinal studies for reproducible findings and drawing robust inferences.

Mild Behavioral Impairment (MBI) leverages later-life emergent and persistent neuropsychiatric symptoms (NPS) to identify a high-risk group for incident dementia. Phosphorylated tau (p-tau) is a hallmark biological manifestation of Alzheimer disease (AD). We investigated associations between MBI and tau accumulation in early-stage AD cortical regions. In 442 Alzheimer\'s Disease Neuroimaging Initiative participants with normal cognition or mild cognitive impairment, MBI status was determined alongside corresponding p-tau and Aβ. Two meta-regions of interest were generated to represent Braak I and III neuropathological stages. Multivariable linear regression modelled the association between MBI as independent variable and tau tracer uptake as dependent variable. Among Aβ positive individuals, MBI was associated with tau uptake in Braak I (β=0.45(0.15), p<.01) and Braak III (β=0.24(0.07), p<.01) regions. In Aβ negative individuals, MBI was not associated with tau in the Braak I region (p=0.11) with a negative association in Braak III (p=.01). These findings suggest MBI may be a sequela of neurodegeneration, and can be implemented as a cost-effective framework to help improve screening efficiency for AD.

The Mild Behavioral Impairment (MBI) concept was developed to determine whether late-onset persistent neuropsychiatric symptoms (NPSs) may be early manifestations of cognitive decline. Our study aims to investigate the prevalence and differentiating features of MBI with respect to major neurocognitive disorders (MNDs) and primary psychiatric disorders (PPDs). A total of 144 elderly patients who were referred to our psychogeriatric outpatient service were recruited. The severity of mental illness was evaluated by means of the Clinical Global Impression Severity scale, the severity of psychopathology was evaluated by means of the Brief Psychiatric Rating Scale (BPRS), and overall functioning was evaluated by means of the Global Assessment of Functioning scale. The sample included 73 (50.6%) patients with PPDs, 40 (27.8%) patients with MBI, and 31 (21.5%) patients with MNDs. Patients with MNDs reported the greatest severity of mental illness, the highest BPRS Total, Psychosis, Activation, and Negative Symptom scores, and the lowest functioning. Patients with MBI and PPDs had comparable levels of severity of mental illness and overall functioning, but MBI patients reported higher BPRS Total and Negative Symptom scores than PPD patients. Patients with MBI frequently reported specific clinical features, including a higher severity of apathy and motor retardation. These features merit further investigation since they may help the differential diagnosis between MBI and PPDs.

Dementia assessment includes cognitive and behavioral testing with informant verification. Conventional testing is resource-intensive, with uneven access. Online unsupervised assessments could reduce barriers to risk assessment. The aim of this study was to assess the relationship between informant-rated behavioral changes and participant-completed neuropsychological test performance in older adults, both measured remotely via an online unsupervised platform, the Brain Health Registry (BHR).
Observational cohort study.
Community-dwelling older adults participating in the online BHR. Informant reports were obtained using the BHR Study Partner Portal.
The final sample included 499 participant-informant dyads.
Participants completed online unsupervised neuropsychological assessment including Forward Memory Span, Reverse Memory Span, Trail Making B, and Go/No-Go tests. Informants completed the Mild Behavioral Impairment Checklist (MBI-C) via the BHR Study Partner portal. Cognitive performance was evaluated in MBI+/- individuals, as was the association between cognitive scores and MBI symptom severity.
Mean age of the 499 participants was 67, of which 308/499 were females (61%). MBI + status was associated with significantly lower memory and executive function test scores, measured using Forward and Reverse Memory Span, Trail Making Errors and Trail Making Speed. Further, significant associations were found between poorer objectively measured cognitive performance, in the domains of memory and executive function, and MBI symptom severity.
These findings support the feasibility of remote, informant-reported behavioral assessment utilizing the MBI-C, supporting its validity by demonstrating a relationship to online unsupervised neuropsychological test performance, using a previously validated platform capable of assessing early dementia risk markers.

OBJECTIVE: To investigate potential risk factors for mild behavioral impairment (MBI) among non-demented geriatrics.
METHODS: Population-based, cross-sectional survey.
METHODS: Taiwan Alzheimer Disease Association (TADA) Database.
METHODS: Participants were selected by multistage random sampling of all Taiwan counties. They received in-person interviews between December 2011 and March 2013.
METHODS: Demographic data, lifestyle and habits, medical comorbidities, cognitive status measured by the Taiwanese Mini-Mental Status Examination (TMSE) and presence of MCI of the participants were collected. Subjects were distributed to the MBI and non-MBI groups. These factors had been evaluated for their effects on MBI in the univariate and multivariable logistic regression models.
RESULTS: In total, 6,196 non-demented participants aged 65 years or older, including 409 MBI and 5,787 non-MBI participants, were recruited. After adjustment for age, sex, education, body mass index, lifestyle and habits, medical comorbidities, and MCI, good sleep was associated with lower risk of MBI (OR 0.09, 95% CI 0.07 - 0.12). Low body weight (OR 2.01, 95% CI 1.21-3.33), low-to-medium education (OR 1.40, 95%CI 1.06-1.85; OR 2.32, 95% CI 1.67-3.21), medical comorbidities of hypertension (OR 1.56, 95% CI 1.25-1.95), hyperlipidemia (OR 1.29, 95% CI 1.00-1.67), cancer (OR 2.05, 95% CI 1.37-3.06) were significantly associated with increased MBI risk. MCI neither increased nor decreased risk of MBI (OR 1.00, 95% CI 0.76-1.32).
CONCLUSIONS: Good sleep was associated with lower MBI risk. Underweight, lower education, medical comorbidities of cancer, hypertension, hyperlipidemia were predictive of MBI.

Mild behavioral impairment (MBI) describes later life acquired, sustained neuropsychiatric symptoms (NPS) in cognitively normal individuals or those with mild cognitive impairment (MCI), as an at-risk state for incident cognitive decline and dementia. We developed an operational definition of MBI and tested whether the presence of MBI was related to caregiver burden in patients with subjective cognitive decline (SCD) or MCI assessed at a memory clinic.
MBI was assessed in 282 consecutive memory clinic patients with SCD (n = 119) or MCI (n = 163) in accordance with the International Society to Advance Alzheimer\'s Research and Treatment - Alzheimer\'s Association (ISTAART-AA) research diagnostic criteria. We operationalized a definition of MBI using the Neuropsychiatric Inventory Questionnaire (NPI-Q). Caregiver burden was assessed using the Zarit caregiver burden scale. Generalized linear regression was used to model the effect of MBI domains on caregiver burden.
While MBI was more prevalent in MCI (85.3%) than in SCD (76.5%), this difference was not statistically significant (p = 0.06). Prevalence estimates across MBI domains were affective dysregulation (77.8%); impulse control (64.4%); decreased motivation (51.7%); social inappropriateness (27.8%); and abnormal perception or thought content (8.7%). Affective dysregulation (p = 0.03) and decreased motivation (p=0.01) were more prevalent in MCI than SCD patients. Caregiver burden was 3.35 times higher when MBI was present after controlling for age, education, sex, and MCI (p < 0.0001).
MBI was common in memory clinic patients without dementia and was associated with greater caregiver burden. These data show that MBI is a common and clinically relevant syndrome.

Apathy is common in neurocognitive disorders (NCDs) such as Alzheimer\'s disease and mild cognitive impairment. Although the definition of apathy is inconsistent in the literature, apathy is primarily defined as a loss of motivation and decreased interest in daily activities.
The Alzheimer\'s Association International Society to Advance Alzheimer\'s Research and Treatment (ISTAART) Neuropsychiatric Syndromes Professional Interest Area (NPS-PIA) Apathy workgroup reviewed the latest research regarding apathy in NCDs.
Progress has recently been made in three areas relevant to apathy: (1) phenomenology, including the use of diagnostic criteria and novel instruments for measurement, (2) neurobiology, including neuroimaging, neuropathological and biomarker correlates, and (3) interventions, including pharmacologic, nonpharmacologic, and noninvasive neuromodulatory approaches.
Recent progress confirms that apathy has a significant impact on those with major NCD and those with mild NCDs. As such, it is an important target for research and intervention.