Validating the Mild Behavioral Impairment Checklist in a Cognitive Clinic: Comparisons With the Neuropsychiatric Inventory Questionnaire.

OBJECTIVE: To compare the utility of the Mild Behavioral Impairment-Checklist (MBI-C) and Neuropsychiatric Inventory Questionnaire (NPI-Q) to capture NPS in subjective cognitive decline (SCD), mild cognitive impairment (MCI), and dementia. METHODS: In this cross-sectional memory clinic study, linear regression models compared MBI-C (n = 474) and NPI-Q (n = 1040) scores in relation to Montreal Cognitive Assessment (MoCA) score. RESULTS: MBI prevalence was 37% in subjective cognitive decline, 54% in mild cognitive impairment, and 62% in dementia. Worse diagnostic status was associated with higher MBI-C and NPI-Q score (P < .001), lower MoCA (P < .001), and greater age (P < .001). Higher MBI-C (ß -.09; 95% CI -.13, -.05) and NPI-Q (ß -.17; 95% CI -.23, -.10) scores were associated with lower MoCA scores, with psychosis most strongly associated (ß -1.11; 95% CI -1.56, -.65 vs ß -1.14; 95% CI -1.55, -.73). CONCLUSIONS: The MBI-C captures global and domain-specific NPS across cognitive stages. Both the MBI-C and NPI-Q have utility in characterizing NPS.

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.

Diagnosing Alzheimer's Disease from Circulating Blood Leukocytes Using a Fluorescent Amyloid Probe.

BACKGROUND: Toxic amyloid-ß (Aß) peptides aggregate into higher molecular weight assemblies and accumulate not only in the extracellular space, but also in the walls of blood vessels in the brain, increasing their permeability, and promoting immune cell migration and activation. Given the prominent role of the immune system, phagocytic blood cells may contact pathological brain materials. OBJECTIVE: To develop a novel method for early Alzheimer's disease (AD) detection, we used blood leukocytes, that could act as "sentinels" after trafficking through the brain microvasculature, to detect pathological amyloid by labelling with a conformationally-sensitive fluorescent amyloid probe and imaging with confocal spectral microscopy. METHODS: Formalin-fixed peripheral blood mononuclear cells (PBMCs) from cognitively healthy control (HC) subjects, mild cognitive impairment (MCI) and AD patients were stained with the fluorescent amyloid probe K114, and imaged. Results were validated against cerebrospinal fluid (CSF) biomarkers and clinical diagnosis. RESULTS: K114-labeled leukocytes exhibited distinctive fluorescent spectral signatures in MCI/AD subjects. Comparing subjects with single CSF biomarker-positive AD/MCI to negative controls, our technique yielded modest AUCs, which improved to the 0.90 range when only MCI subjects were included in order to measure performance in an early disease state. Combining CSF Aß42 and t-Tau metrics further improved the AUC to 0.93. CONCLUSION: Our method holds promise for sensitive detection of AD-related protein misfolding in circulating leukocytes, particularly in the early stages of disease.

Final 2 year results of the vascular imaging of acute stroke for identifying predictors of clinical outcome and recurrent ischemic eveNts (VISION) study.

UNLABELLED: Among patients with ischemic stroke, little attention has been paid to differentiation between stroke progression and recurrence. We assessed the role of MR imaging in predicting stroke progression, recurrent stroke, and death within 2 years of symptom onset. METHODS: Ischemic stroke or TIA patients were prospectively enrolled. They were examined within 12 hours and had a stroke MR completed within 24 hours of symptom onset. Patients were closely followed neurologically and examined if there was any deterioration in neurological status. Relationships between baseline clinical and imaging factors and outcomes were assessed. We also examined whether baseline stroke/TIA severity (NIHSS 0-5 versus NIHSS > 5) modified these relationships. RESULTS: A total of 334 patients were enrolled. The overall rates of progression, 2-year recurrence, and 2-year death were 8.7%, 8.0%, and 6.6%, respectively. Event rates were similar among patients with mild compared to more severe strokes: 8.3% versus 9.5% (p = 0.73) for progression, and 7.3% versus 9.9% (p = 0.59) for recurrence. The effect of baseline glucose > 8 mmol/l was consistent in predicting stroke progression, recurrent stroke and death, regardless of baseline stroke severity. In multivariable analyses, DWI lesion and intracranial occlusion predicted stroke progression only in the minor stroke/TIA group; symptomatic Internal Carotid Artery (ICA) stenosis predicted stroke recurrence only in the minor stroke/TIA group. CONCLUSIONS: In a prospective study with early assessment and imaging we have found that stroke progression is different than stroke recurrence. Different imaging factors predict stroke progression versus stroke recurrence. Baseline hyperglycemia, a potentially modifiable factor, consistently predicted all three outcomes (stroke progression, recurrent stroke or death) regardless of baseline stroke severity.

Understanding the impact of the COVID-19 pandemic on well-being and virtual care for people living with dementia and care partners living in the community.

The COVID-19 pandemic has necessitated public health measures that have impacted the provision of care for people living with dementia and their families. Additionally, the isolation that results from social distancing may be harming well-being for families as formal and informal supports become less accessible. For those living with dementia and experiencing agitation, social distancing may be even harder to maintain, or social distancing could potentially aggravate dementia-related neuropsychiatric symptoms. To understand the lived experience of social and physical distancing during the COVID-19 pandemic in Canada, we remotely interviewed 21 participants who normally attend a dementia specialty clinic in Calgary, Alberta, during a period where essential businesses were closed and health care had abruptly transitioned to telemedicine. A reflexive thematic analysis was used to analyze the interview and field note data. The impacts of the public health measures in response to the pandemic emerged through iterative analysis in three main categories of experience: (1) personal, (2) health services, and (3) health status (of both persons living with dementia and care partner). Isolation and mental health needs emerged as important impacts to family experiences. This in-depth understanding of the needs and experiences of the pandemic for people living with dementia suggests that innovative means are urgently needed to facilitate provision of remote medicine and also social interaction and integration.