Neuropsychiatric symptoms: Risk factor or disease marker? A study of structural imaging biomarkers of Alzheimer's disease and incident cognitive decline.

Neuropsychiatric symptoms (NPS) are risk factors for Alzheimer's disease (AD) but can also manifest secondary to AD pathology. Mild behavioral impairment (MBI) refers to later-life emergent and persistent NPS that may mark early-stage AD. To distinguish MBI from NPS that are transient or which represent psychiatric conditions (non-MBI NPS), we investigated the effect of applying MBI criteria on NPS associations with AD structural imaging biomarkers and incident cognitive decline. Data for participants (n = 1273) with normal cognition (NC) or mild cognitive impairment (MCI) in the National Alzheimer's Coordinating Center Uniform Data Set were analyzed. NPS status (MBI, non-MBI NPS) was derived from the Neuropsychiatric Inventory Questionnaire and psychiatric history. Normalized measures of bilateral hippocampal (HPC) and entorhinal cortex (EC) volume, and AD meta-region of interest (ROI) mean cortical thickness were acquired from T1-weighted magnetic resonance imaging scans. Multivariable linear and Cox regressions examined NPS associations with imaging biomarkers and incident cognitive decline, respectively. MBI was associated with lower volume and cortical thickness in all ROIs in both NC and MCI, except for EC volume in NC. Non-MBI NPS were only associated with lower HPC volume in NC. Although both of the NPS groups showed higher hazards for MCI/dementia than No NPS, MBI participants showed more rapid decline. Although both types of NPS were linked to HPC atrophy, only NPS that emerged and persisted in later-life, consistent with MBI criteria, were related to AD neurodegenerative patterns beyond the HPC. Moreover, MBI predicted faster progression to dementia than non-MBI NPS.

Functional connectivity and mild behavioral impairment in dementia-free elderly.

Background: Mild behavioral impairment (MBI) is a syndrome that uses later-life emergent and persistent neuropsychiatric symptoms (NPS) to identify a group at high risk for incident dementia. MBI is associated with neurodegenerative disease markers in advance of syndromic dementia. Functional connectivity (FC) correlates of MBI are understudied and could provide further insights into mechanisms early in the disease course. We used resting-state functional magnetic resonance imaging (rs-fMRI) to test the hypothesis that FC within the default mode network (DMN) and salience network (SN) of persons with MBI (MBI+) is reduced, relative to those without (MBI-). Methods: From two harmonized dementia-free cohort studies, using a score of ≥6 on the MBI Checklist to define MBI status, 32 MBI+ and 63 MBI- individuals were identified (mean age: 71.7 years; 54.7% female). Seed-based connectivity analysis was implemented in each MBI group using the CONN fMRI toolbox (v20.b), with the posterior cingulate cortex (PCC) as the seed region within the DMN and anterior cingulate cortex (ACC) as the seed within the SN. The average time series from the PCC and ACC were used to determine FC with other regions within the DMN (medial prefrontal cortex, lateral inferior parietal cortex) and SN (anterior insula, supramarginal gyrus, rostral prefrontal cortex), respectively. Age, sex, years of education, and Montreal Cognitive Assessment scores were included as model covariates. The false discovery rate approach was used to correct for multiple comparisons, with a p-value of .05 considered significant. Results: For the DMN, MBI+ individuals exhibited reduced FC between the PCC and the medial prefrontal cortex, compared to MBI-. For the SN, MBI+ individuals exhibited reduced FC between the ACC and left anterior insula. Conclusion: MBI in dementia-free older adults is associated with reduced FC in networks known to be disrupted in dementia. Our results complement the evidence linking MBI with Alzheimer's disease biomarkers. Highlights: Resting-state functional magnetic resonance imaging was completed in 95 dementia-free persons from FAVR and COMPASS-ND studies.Participants were stratified by informant-rated Mild Behavioral Impairment Checklist (MBI-C) score, ≥6 for MBI+.MBI+ participants showed reduced functional connectivity (FC) within the default mode network and salience network.These FC changes are consistent with those seen in early-stage Alzheimer's disease.MBI may help identify persons with early-stage neurodegenerative disease.

Progression to Dementia or Reversion to Normal Cognition in Mild Cognitive Impairment as a Function of Late-Onset Neuropsychiatric Symptoms.

BACKGROUND AND OBJECTIVES: Mild cognitive impairment (MCI) is an at-risk state for dementia; however, not all individuals with MCI transition to dementia, and some revert to normal cognition (NC). Here, we investigate whether mild behavioral impairment (MBI), the late-life onset of persistent neuropsychiatric symptoms (NPS), improves the prognostic specificity of MCI. METHODS: Participants with MCI from the National Alzheimer's Coordinating Center Uniform Data Set were included. NPS were operationalized with the Neuropsychiatric Inventory Questionnaire to identify participants without NPS and those with MBI (persistent, late-onset NPS). Individuals with late-onset NPS not meeting the MBI persistence criterion (NPS_NOT_MBI) were retained for secondary analyses. Progression to dementia, stable MCI, and reversion to NC after 3 years of follow-up were defined per National Institute on Aging-Alzheimer's Association and Petersen criteria. RESULTS: The primary sample consisted of 739 participants (NPS- n = 409 and MBI+ n = 330; 75.16 ± 8.6 years old, 40.5% female). After 3 years, 238 participants (33.6%) progressed to dementia, and 90 (12.2%) reverted to NC. Compared to participants without NPS, participants with MBI were significantly more likely to progress to dementia (adjusted odds ratio [AOR] 2.13, 95% CI 1.52-2.99), with an annual progression rate of 14.7% (vs 8.3% for participants with MCI without NPS). Compared to participants without NPS, participants with MBI were less likely to revert to NC (AOR 0.48, 95% CI 0.28-0.83, 2.5% vs 5.3% annual reversion rate). The NPS_NOT_MBI group (n = 331, 76.5 ± 8.6 years old, 45.9% female) were more likely to progress to dementia (AOR 2.18, 95% CI 1.56-3.03, 14.3% annual progression rate) but not less likely to revert to NC than those without NPS. Accordingly, both NPS_NOT_MBI and MBI+ participants had lower Mini-Mental State Examination scores than NPS- participants after 3 years. DISCUSSION: Late-onset NPS improve the specificity of MCI as an at-risk state for progression to dementia. However, only persistent late-onset NPS are associated with a lower likelihood of reversion to NC, with transient NPS (i.e., NPS_NOT_MBI) not differing from the NPS- group. Clinical prognostication can be improved by incorporating late-onset NPS, especially those that persist (i.e., MBI), into risk assessments. Clinical trials may benefit from enrichment with these higher-risk participants with MCI.

Anticoagulant and antiplatelet use in seniors with chronic subdural hematoma: Systematic review.

OBJECTIVE: To address whether to restart older patients on anticoagulants or antiplatelet agents in the setting of a chronic subdural hematoma (cSDH). METHODS: This is an update of a previous review (searched until July 2012). Medline, EMBASE, ISI Web of Knowledge, Google Scholar, PLOS, and the Cochrane Register for Systematic Reviews databases were searched from January 2012 to December 2016. Studies included older adults (those over 65 years) experiencing traumatic subdural hematoma or cSDH who were on anticoagulation or antiplatelet agents. RESULTS: Seven studies were included (mean age 72 years). Four out of 7 studies provided combined data on anticoagulants or antiplatelet use. Only one study found anticoagulant or antiplatelet agent use to be a significant factor for cSDH rebleeding. Two studies considered anticoagulant use only and both reported similar increased odds of rebleeding (odds ratio [OR] 1.75, 95% confidence interval [CI] 0.18-16.86; OR 2.7 95% CI 1.42-6.96). Antiplatelets were not found to be associated with rebleeding. Ideal timing to resume anticoagulants or antiplatelets was unclear. CONCLUSIONS: Anticoagulant medication was associated with increased rebleeding risk in older adults with cSDH. However, antiplatelet medication was not associated with increased risk of rebleeding.