Faculty Bibliography

OBJECTIVE: Our aim is to determine the clinical correlates of impaired insight in patients with mild cognitive impairment (MCI) by examining its impact on cognition, functional status, neuropsychiatric symptoms, and caregiver burden. METHODS: The study involved 75 patients with MCI and their caregivers. Patients and caregivers underwent a comprehensive evaluation including the Clinical Dementia Rating, memory tests, and the Functional Assessment Questionnaire. Behavioral symptoms were assessed by the Neuropsychiatric Inventory, caregiver burden by the Zarit Burden Inventory, and insight by comparing self-report on the AD8 dementia screening tool to informant collateral. Patients were asked about their perceptions of their memory, and answers were compared with informants' responses. Patient mood was assessed with the Hospital Anxiety Depression Scale. RESULTS: There was a significant difference in AD8 scores among patients who retained versus lacked insight. Zarit Burden Inventory scores showed a significant rise as patient insight declined; the burden appeared greater on spouse versus non-spouse caregivers. Patients with poor insight had significantly worse ratings in Clinical Dementia Rating domains of personal care and judgment, while patients who retained insight had significantly higher depression and anxiety. Insight impairment was associated with worse caregiver mood. CONCLUSIONS: Decreased patient awareness for cognitive problems was significantly associated with higher caregiver burden, independent of neuropsychiatric symptoms, functional abilities, and cognition. Personal care, judgment, and problem-solving skills could contribute to caregiver burden. Increased awareness seemed a source of patient depression and anxiety. The research highlights the need to focus on the needs of MCI caregivers and to incorporate psychosocial assessments of caregiver-patient dyads into office visits.

Home health care agencies are increasingly taking care of sicker, older patients with greater comorbidities. However, they are unequipped to appropriately manage these older adults, particular persons living with dementia (PLWD). We therefore developed the Dementia Symptom Management at Home (DSM-H) Program, a bundled interprofessional intervention, to improve the care confidence of providers, and quality of care delivered to PLWD and their caregivers. We implemented the DSM-H with 83 registered nurses, physical therapists, and occupational therapists. Overall, there was significant improvement in pain knowledge (5.9%) and confidence (26.5%), depression knowledge (14.8%) and confidence (36.1%), and neuropsychiatric symptom general knowledge (16.8%), intervention knowledge (20.9%), attitudes (3.4%) and confidence (27.1%) at a statistical significance of (P < .0001). We also found significant differences between disciplines. Overall, this disseminable program proved to be implementable and improve clinician's knowledge and confidence in caring for PLWD, with the potential to improve quality of care and quality of life, and decrease costs.

OBJECTIVE: Characterize the onset and timing of cognitive decline in Parkinson disease (PD) from the first recognizable stage of cognitively symptomatic PD-mild cognitive impairment (PD-MCI) to PD dementia (PDD). Thirty-nine participants progressed from PD to PDD and 25 remained cognitively normal. METHODS: Bayesian-estimated disease-state models described the onset of an individual's cognitive decline across 12 subtests with a change point. RESULTS: Subtests measuring working memory, visuospatial processing ability, and crystalized memory changed significantly 3 to 5 years before their first nonzero Clinical Dementia Rating and progressively worsened from PD to PD-MCI to PDD. Crystalized memory deficits were the hallmark feature of imminent conversion of cognitive status. Episodic memory tasks were not sensitive to onset of PD-MCI. For cognitively intact PD, all 12 subtests showed modest linear decline without evidence of a change point. CONCLUSIONS: Longitudinal disease-state models support a prodromal dementia stage (PD-MCI) marked by early declines in working memory and visuospatial processing beginning 5 years before clinical diagnosis of PDD. Cognitive declines in PD affect motor ability (bradykinesia), working memory, and processing speed (bradyphrenia) resulting in PD-MCI where visuospatial imagery and memory retrieval deficits manifest before eventual development of overt dementia. Tests of episodic memory may not be sufficient to detect and quantify cognitive decline in PD.

Objective: To evaluate structural volumetric changes in basal gangliathalamocortical (BGTC) regions related to cognitive function in Parkinson's disease (PD) patients with and without cognitive impairment. Methods: In a cohort of 35 PD patients (24 males, 11 females) and 31 controls (11males, 20 females), we evaluated the volumes of the following BGTC structures: lateral and medial orbitofrontal cortex, anterior cingulate cortex, and caudate nuclei based on automated segmentation of T1- weighted 3T brain MRI images with FreeSurfer 5.3. All images were manually inspected for accuracy of segmentation. SPM12 was used to generate intracranial volumes (ICV) for normalization of all measured structures. All subjects underwent clinical and neuropsychological assessments to determine cognitive status. Results: Based on a battery of neuropsychological tests and a clinicians' multidisciplinary consensus conference, we classified 15 PD subjects as cognitively impaired (PD-impaired; 11 males, 4 females; MOCA 22.9 +/- 3.63) and 20 as cognitively normal (PD-NC; 13 males, 7 females; MOCA 27 +/- 1.86). PD-impaired had smaller left caudate (0.22 +/- 0.02 vs. 0.25 +/- 0.03, p<0.05) and smaller right lateral orbitofrontal cortex than controls (0.45 +/- 0.04 vs. 0.50 +/- 0.05, p<0.05). PD-NC showed a trend towards smaller left caudate as compared to controls (0.23 +/- 0.02 vs. 0.25 +/- 0.03, p=0.05). Compared to PD-NC, PD-impaired had smaller right lateral orbitofrontal volumes (0.45 +/- 0.04 vs. 0.50 +/- 0.06, p<0.05). Conclusion: PD patients with cognitive impairment have more widespread structural changes in basal ganglia-thalamocortical circuits than PD without cognitive impairment. Automated volumetric measures of such cortical volumes may serve as a potential biomarker of cognitive status of PD patients

Cognitive and physical aspects of functionality are closely related. However, whether physical decline differs by dementia type and progression rate is debatable. To address these issues, we conducted a longitudinal study of 766 older adults whose physical performance and cognitive status were assessed annually with standard assessment tools [eg, Physical Performance Test, Clinical Dementia Rate (CDR)] for 8 years. Compared with participants who remained cognitively normal, those progressing to later-stage dementia (CDR=1) declined in their mobility by a factor of 2.82 (P<0.001), followed by those who maintained a later-stage diagnosis (slope=-1.84, P<0.001), those progressing from early-stage to later-stage (CDR=0.5 to CDR=1) dementia (slope=-1.20, P<0.001), and those who progressed to early-stage dementia (slope=-0.39, P=0.038) suggesting a steeper physical decline with dementia progression, particularly in those with the fastest disease progression. Although all types of dementia experienced mobility decline, those progressing to non-Alzheimer disease (AD) dementias, especially vascular dementia declined faster than those who remained normal (slope=-2.70, P<0.001) or progressed to AD (slope=-2.18, P<0.001). These associations were better captured by the gait/balance component of physical functionality. Our findings suggest that rapidly progressing dementia patients particularly those with non-AD subtypes should be targeted for interventions to maintain or improve gait/balance and prevent functional decline and disability although AD patients may also benefit.

INTRODUCTION: Dementia with Lewy bodies (DLB) is a challenge to diagnose, particularly outside of expert centers with long delays in diagnosis leading to significant burden to patients and caregivers. While consensus criteria have excellent specificity, there is no standardized way to assess symptoms reducing sensitivity. We developed the Lewy Body Composite Risk Score (LBCRS) from autopsy-verified cases to improve the ability to detect DLB in clinic and research populations. METHODS: The LBCRS was tested in a consecutive series of 256 patients compared with the Clinical Dementia Rating and gold standard measures of cognition, motor symptoms, function, and behavior. Psychometric properties including floor and ceiling effects; concurrent, construct, and known-groups validity, and internal consistency of the LBCRS were determined. Receiver operator characteristic (ROC) curves assessed the ability of LBCRS to differentiate: (a) DLB from Alzheimer's disease (AD); (b) DLB from all dementia, and (c) Mild cognitive impairment (MCI) due to DLB from MCI due to AD. The LBCRS was completed independent of the clinical evaluation. RESULTS: Mean LBCRS scores were significantly different between DLB and AD (6.1+/-2.0 vs. 2.4+/-1.3, p<.001) and between MCI-DLB vs MCI-AD (3.2+/-0.9 vs. 1.0+/-0.8, p<.001). The LBCRS was able to discriminate DLB from other causes of dementia. Using a cut-off score of 3, areas under ROC for DLB vs. AD = 0.93 (0.89-0.98), and for MCI-DLB vs. MCI-AD = 0.96 (0.91-1.0). DISCUSSION: The LBCRS increases diagnostic probability that Lewy body pathology is contributing to the dementia syndrome and should improve clinical detection and enrollment for clinical trials.

Background: Cognitive and physical impairments are common, coexisting chronic conditions that have complex, and often bidirectional relationships in which presence of one has the potential to initiate, synergize, or result from the other. Understanding how the processes that lead to dementia and physical disability interrelate at early stages of dysfunction affords the opportunity for preventative or restorative interventions. We evaluated both crosssectional and longitudinal associations between cognitive and physical function to better understand the directionality of the relationships. Methods: Data from 2 studies of cognitive and functional aging were used: a longitudinal study conducted at the Knight ADRC at Washington University in St. Louis (766 individuals followed up for up to 8 years) and a cross-sectional study conducted at NYU (272 individuals). Both studies enrolled community-dwelling individuals over the age of 50 who underwent cognitive and physical assessments tapping into global (e.g., CDR-SB, MoCA, AD8) and individual cognitive domains (e.g., Naming, Trailmaking) and physical performance (PP) measures (e.g., grip-strength (GS), muscle mass (MM)). Formal diagnoses were available in the longitudinal study, while the cross-sectional studies established impaired vs. non-impaired. Associations were investigated with regression analysis techniques. Results: GS impairment was associated with lower MoCA (B=-2.0, p=0.011); when combined with low MM the likelihood of dual cognitive-physical impairment increased. The effect of low GS on global cognition doubled when poor PP was also present (indicator of later stage physical impairment; B=-3.77, p<0.001). However, while the rate of decline in cognitive (various measures; p<0.001) and physical (slope=-1.22, p<0.001) performance was sharper in those with baseline cognitive impairment, baseline physical impairment had no significant impact on either cognitive or physical decline. Cross-sectionally, GS impacted MoCA through poor PP (indirect effect=0.018, p<0.01). When type of dementia was considered, vascular dementia declined faster than controls (slope=-2.70, p<0.001) or AD (slope=-2.18, p<0.001). Conclusions: Earlier indicators of physical dysfunction (i.e. low GS) are associated with cognitive impairment with evidence for a dose-response operating in the direction of cognitive-to-physical impairment (although the reverse cannot be ruled out). Targeted interventions to maintain physical functionality and strength in individuals with dementia, particularly vascular dementia may mitigate future decline and disability

Background: Approximately 5.2 million Americans are affected by Alzheimer's disease (AD), with another 1.3 million individuals affected by Lewy Body Dementia (LBD), the second most common cause. Nearly 60% of dementia caregivers rate emotional stress of caregiving as high or very high, and this will only increase as more resources are required with dementia progression. As such, the grieving process for caregivers likely begins early, as adult children and spouses often take on a multitude of new responsibilities previously managed by the patient, often prior to the formal diagnosis. Adverse outcomes for the caregiver (e.g., stress, depression and poor health) directly lead to declines in quality of life for both the patient and the caregiver. Improved understanding of caregiver grief will provide important information to develop interventions for the early identification of caregiver grief. We examine the sensitivity of the underlying constructs measured by the Marwit-Meuser Caregiver Grief Inventory Short Form (MMCGI-SF), a common self-reported measure of caregiver grief. Methods: An online survey of dementia caregivers [AD (n=64), LBD (n=350)] was completed including the MMCGI-SF. The MMCGI-SF contains three constructs: Personal Sacrifice Burden, Heartfelt Sadness, and Worry and Felt Isolation. We conducted confirmatory factor analyses to determine goodness of fit testing whether this model of grief holds for spouse and child primary caregivers for patients with AD and LBD. Results: Caregiver ages were equivalent (M=62.0(610.5) as were patient dementia stage (CDR Box Scores; M=10.4(64.4). Confirmatory factor analysis rejected the current MMCGI-SF model for both groups. The model was improved by separating the construct of "Worry and Felt Isolation" into separate categories in both AD: CFI = .88, NFI = .89, RMSEA = .091 (.062-.117) and LBD: CFI = .93, NFI = .92, RMSEA = .072 (.063-.080). Conclusions: Isolation was shown to be an important component of grief state for spouse and adult child caregivers, particularly caregivers of LBD. This may be due to constellation of cognitive, motor, behavioral, and autonomic features that distinguish LBD from AD. We believe that changes in healthcare and the extended lifespan of patients have led to the need for caregiver interventions that specifically targeting isolation

Background: There are significant cultural differences regarding knowledge and perceptions of Alzheimer disease (AD) potentially leading to delays in diagnosis and treatment. There is a need to better understand differences between Caucasian and African American older adults regarding their knowledge of AD, perceived access to care, health beliefs, and willingness to discuss memory problems with providers. Methods: A population-based survey of 1,039 non-demented older adults across three counties (urban, suburban, rural) had a mean age of 62.7+10.2 (range, 50-97); 94% high school education; 67% women, 86% white, mean Short Blessed Test = 1.7+2.2. Constructs from behavioral models including Health Belief Model, Self-efficacy, and Social Support were compared between White (n=863) and Black (n=121) respondents attitudes and perceptions regarding dementia screening. Results: African American older adults were less likely to use the internet for health information (p=.005) and more dependent on public transportation (p<.001) for doctor visits. Black older adults were more likely to believe memory loss a part of normal aging (p=.01), had less knowledge about dementia (p=.003) and its consequences (p=.002), were less likely to know their healthcare provider could test for dementia (p=.004), had lower perceived accessibility of dementia-related services (p=.001), and reported lower self-efficacy to discuss memory problems with their providers (p=.006). Health Belief model constructs differed with African Americans reporting higher perceived barriers (p=.003) and lower perceived severity (p=.03). Logistic regression models showed that intention for screening is predicted by white race (OR 4.28); male gender (OR 2.10), self-reported anxiety (OR 1.44), self-efficacy to discuss memory problems (OR 2.72), knowledge their MD can test memory (OR 1.70), and social support (OR 1.23). Conclusions: We found significant differences in socioeconomic factors, utilization and accessibility to medical services, and knowledge of dementia between Caucasians and African- Americans. Although older African-Americans reported intention to have their memory evaluated, actual screening behaviors were more likely to occur in individuals with high self-efficacy for discussing memory problems, perceived accessibility to dementia services, already present preventive health behaviors, and a social support system. These constructs can be used to develop interventions to evaluate and improve cognitive health in African Americans