Case series of mild behavioral impairment: toward an understanding of the early stages of neurodegenerative diseases affecting behavior and cognition.

Mild behavioral impairment (MBI) is characterized by later life acquired, sustained, and impactful neuropsychiatric symptoms (NPS) of any severity that cannot be better accounted for by other formal medical and psychiatric nosology. MBI is an "at risk" state for incident cognitive decline and dementia, and for some, MBI is the index manifestation of neurodegeneration, observed in advance of cognitive impairment. Initially described in Frontotemporal Dementia (FTD), MBI evolved to describe a preclinical stage of all cause dementia, and has been operationalized in the International Society to Advance Alzheimer's Research and Treatment-Alzheimer's Association (ISTAART-AA) proposed research diagnostic criteria. Here, we describe three cases in which patients diagnosed with a variety of dementing conditions initially presented with NPS to the Cognitive Neurosciences Clinic at the University of Calgary, Canada. All patients described in our series were given a final diagnosis of dementia; the etiology supported by clinical, cognitive, and neuroimaging findings. In all three cases, the progression to dementia was preceded by NPS that meet criteria for MBI. With these examples, we are able to illustrate that MBI can represent a premonitory stage of dementia of different etiologies. These cases demonstrate early use of the MBI checklist (MBI-C). The cases presented in this series serve as examples of NPS as early manifestations of dementia. Our case examples include both FTD and AD, and demonstrate that before a diagnosis of a neurodegenerative disease is considered, often patients will be diagnosed with and treated for a psychiatric condition. These early NPS can be characterized within the domains outlined in the ISTAART-AA MBI criteria, and detected with the MBI-C, which may help clinicians consider neurodegenerative disease in the differential diagnosis of later life onset psychiatric symptomatology.

Prevalence of mild behavioral impairment in mild cognitive impairment and subjective cognitive decline, and its association with caregiver burden.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

A pragmatic dementia risk score for patients with mild cognitive impairment in a memory clinic population: Development and validation of a dementia risk score using routinely collected data.

Introduction: This study aimed to develop and validate a 3-year dementia risk score in individuals with mild cognitive impairment (MCI) based on variables collected in routine clinical care. Methods: The prediction score was trained and developed using data from the National Alzheimer's Coordinating Center (NACC). Selection criteria included aged 55 years and older with MCI. Cox models were validated externally using two independent cohorts from the Prospective Registry of Persons with Memory Symptoms (PROMPT) registry and the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Results: Our Mild Cognitive Impairment to Dementia Risk (CIDER) score predicted dementia risk with c-indices of 0.69 (95% confidence interval [CI] 0.66-0.72), 0.61 (95% CI 0.59-0.63), and 0.72 (95% CI 0.69-0.75), for the internally validated and the external validation PROMPT, and ADNI cohorts, respectively. Discussion: The CIDER score could be used to inform clinicians and patients about the relative probabilities of developing dementia in patients with MCI.

The Mild Behavioral Impairment Checklist (MBI-C): A Rating Scale for Neuropsychiatric Symptoms in Pre-Dementia Populations.

BACKGROUND: Mild behavioral impairment (MBI) is a construct that describes the emergence at ≥50 years of age of sustained and impactful neuropsychiatric symptoms (NPS), as a precursor to cognitive decline and dementia. MBI describes NPS of any severity, which are not captured by traditional psychiatric nosology, persist for at least 6 months, and occur in advance of or in concert with mild cognitive impairment. While the detection and description of MBI has been operationalized in the International Society to Advance Alzheimer's Research and Treatment - Alzheimer's Association (ISTAART-AA) research diagnostic criteria, there is no instrument that accurately reflects MBI as described. OBJECTIVE: To develop an instrument based on ISTAART-AA MBI criteria. METHODS: Eighteen subject matter experts participated in development using a modified Delphi process. An iterative process ensured items reflected the five MBI domains of 1) decreased motivation; 2) emotional dysregulation; 3) impulse dyscontrol; 4) social inappropriateness; and 5) abnormal perception or thought content. Instrument language was developed a priori to pertain to non-demented functionally independent older adults. RESULTS: We present the Mild Behavioral Impairment Checklist (MBI-C), a 34-item instrument, which can easily be completed by a patient, close informant, or clinician. CONCLUSION: The MBI-C provides the first measure specifically developed to assess the MBI construct as explicitly described in the criteria. Its utility lies in MBI case detection, and monitoring the emergence of MBI symptoms and domains over time. Studies are required to determine the prognostic value of MBI for dementia development, and for predicting different dementia subtypes.