OBJECTIVE: To determine whether volumetric measures of the hippocampus or entorhinal cortex in combination with other cortical measures can differentiate between cognitively normal individuals and participants with amnestic mild cognitive impairment (MCI). METHODS: T1-weighted magnetic resonance imaging (MRI) data acquired from 46 cognitively normal participants and 50 participants with amnestic MCI as part of the Boston University Alzheimer's Disease Center research registry and the Alzheimer's Disease Neuroimaging Initiative were used in this cross-sectional study. Cortical and subcortical volumes, including hippocampal subfield volumes, were automatically generated from each participant’s structural MRI data using FreeSurfer v6.0. Nominal logistic regression models containing these variables were used to evaluate their ability to identify participants with MCI. RESULTS: A model containing 11 regions of interest (insula, superior parietal cortex, rostral middle frontal cortex, middle temporal cortex, pars opercularis, paracentral lobule, whole hippocampus, subiculum, superior temporal cortex, precentral cortex and caudal anterior cingulate cortex) fit the data best (R2 = 0.7710, whole model test chi square = 102.4794, p < 0.0001). CONCLUSIONS: Volumetric measures acquired from MRI were able to correctly identify most healthy control subjects and those with amnestic MCI using measures of selected medial temporal lobe structures in combination with those from other cortical areas yielding an overall classification of 95.83% for this dataset. These findings support the notion that while clinical features of amnestic MCI may reflect medial temporal atrophy, differences that can be used to distinguish between these two populations are present elsewhere in the brain. This finding further affirming that atrophy can be identified before clinical features are expressed. Additional studies are needed to assess how well other imaging modalities, such as resting state functional connectivity, diffusion imaging, and amyloid and tau position emission tomography (PET), perform in classifying participants who are cognitively normal versus those who are amnestic MCI.

Background: To be able to live independently, older persons can use technology-based health communication (HC) for support, guidance, and contact with health care professionals within their home environment. Informal caregivers who assist in different situations can also find support in their caring role using technology. The study of mobile technologies is an important research area in gerontechnology. Nevertheless, there is a gap of research in technology-based HC utilized by older persons, including preferences related to cognitive impairment (CI) in a home environment. Aim: The overall aim of the thesis was to define the concept and describe experiences of HC within the home environment from a gerontechnological perspective. The aim of Study I was to identify and construct the meaning of HC from the perspective of older persons in need of care in the home environment and their informal caregivers. The aim of Study II was to describe how older persons with CI experienced technology-based HC through the use of a mobile application in order to facilitate a sense of coherence. Method: This thesis has a naturalistic approach. In Study I, the evolutionary model of concept analysis was used, based on a systematic literature review including 29 studies. In Study II, semi-structured interviews were conducted with 16 older persons with CI. The transcripts were analyzed with a deductive thematic analysis. Findings: The defining attributes of the concept HC identified in Study I were: Resources of the recipient, Influence on decisions, and Advantages of tailored information. These attributes led to the following descriptive definition of HC: Tailored information, based on needs and resources of the recipient influence care decisions. The findings of Study II resulted in an overall theme: A technology that supports but creates challenges. Further, the analysis yielded the following three themes, with associated subthemes: Making sense of mobile technologies, Mastering mobile technologies, and Added value to use mobile technologies. Conclusion: Technology-based HC utilized by older persons and their informal caregivers within the home environment emphasizes suiting needs, capacity and preferences to be considered useful. Influences of the context, the home environment also needs to be taken into account when developing technology-based HC and mobile technologies for this purpose.

Cognitive decline is one of the most common symptoms from neuropathology as well as a part of natural aging. While there may be a number of factors that contribute to age-related cognitive decline, previous research has shed a light on the role of chronic hypertension. The effect of hypertension on cognitive decline through small vessel disease is referred to as Vascular Cognitive Impairment and Dementia (VCID). However, the exact molecular pathology behind VCID is not very well understood. Using a non-human primate model of hypertensive aging with the Macaca mulatta, (more commonly known as the Rhesus Macaque) this project builds on previous research implicating collagen IV as part of the cascade of molecular changes that occur in VCID. This project evaluated collagen IV thickness around blood vessels in the corpus callosum and cingulum bundle of normotensive and hypertensive monkeys. as well as determined vessel properties such as total vessel area and perimeter length to evaluate the relationship to scores from the subjects cognitive testing batteries. The results from this project will allow for an examination of the effects on hypertension on vascular properties and possible mechanisms for the development of cognitive impairments. Data collected from this research shows significant differences of collagen IV thickness in the Corpus Callosum between hypertensive and normotensive groups. Similarly, in the cingulum bundle we see that the difference between these groups in collagen IV thickness is trending towards significance. The relationship between average collagen IV densities, blood pressure at perfusion, and cognitive testing scores also showed trending relationships in both the cingulum bundle and the corpus callosum. These results demonstrate how prolonged hypertension can negatively influence cognitive abilities and implicates increases in collagen IV around small vessels in white matter as a significant factor in the molecular cascade which results in cognitive impairment.

The objective of the present study was to evaluate the relationship between a set of cofactors and severity of cognitive impairment, to determine if there were any factors which significantly predicted more severe neurocognitive deficits in persons with AIDS. Twenty-four male volunteers recruited from community groups and physician referrals participated. Subjects completed several self-report questionnaires eliciting information regarding demographics and risk factor variables, in addition to a comprehensive battery of neuropsychological tests. A severity of cognitive impairment summary score was computed for each subject, reflecting both the number of impaired tests and their distance in the impaired direction from normative data. Neither CD4 count, number of months since diagnosis of AIDS, number of AIDS-related illnesses, number of recent stressors, history of head injury/LOC, history of substance use, current or past psychiatric disorder, history of learning disability nor history of other medical illness were found to be significantly related to severity of cognitive impairment in this sample, after controlling for the effects of age, level of education, estimated premorbid IQ and mood status. However, no reliable conclusions could be drawn from this study because the small sample size resulted in an unacceptably low level of statistical power for the desired regression analysis. Exploratory analyses of variance revealed no significant group differences for any of the covariate or cofactor variables when subjects falling at the low, middle, and high ranges of severity of impairment were compared, with the exception of a possible inverse relationship with CD4 count. This was consistent with an exploratory stepwise regression analysis in which only CD4 count entered the model. Some potential limitations of the operational definitions used for the variables in this study were identified, and modifications were suggested. The results of additional exploratory analyses comparing group differences between the "globally impaired" and "unimpaired" subjects (Maj et al., 1994 criteria) on both the covariate and cofactor variables, and neuropsychological test performance, were also discussed.

Indiana University-Purdue University Indianapolis (IUPUI) / Over 5 million older adults have Alzheimer's disease (AD) in the US, and this number is projected to double by 2050. Clinical trials of potential pharmacological treatments for AD have largely shown that once cognitive decline has occurred, targeting AD pathology in the brain does not improve cognition. Therefore, it is likely that the most effective treatments for AD will need to be administered before cognitive symptoms occur, necessitating a biomarker for the early, preclinical stages of AD. Cerebral blood flow (CBF) is a promising early biomarker for AD. CBF is decreased in individuals with AD compared to their normally aging counterparts, and it has been shown that CBF is altered in mild cognitive impairment (MCI) and earlier stages and may occur prior to amyloid or tau aggregation. In addition, CBF can be measured using arterial spin labeled (ASL) MRI, a noninvasive imaging technique that can be safely repeated over time to track prognosis or treatment efficacy. The complex temporal and spatial patterns of altered CBF over the course of AD, as well as the relationships between CBF and AD-specific and -nonspecific factors, will be critical to elucidate in order for CBF to be an effective early biomarker of AD. Here, we begin to characterize the relationships between CBF and risk factors, pathologies, and symptoms of AD. Chapter 1 is a systematic review of published literature that compares CBF in individuals with AD and MCI to CBF in cognitively normal (CN) controls and assesses the relationship between CBF and cognitive function. Chapter 2 reports our original research assessing the relationships between CBF, hypertension, and race/ethnicity in older adults without dementia from the the Indiana Alzheimer’s Disease Research Center (IADRC) and Alzheimer’s Disease Neuroimaging Initiative (ADNI). Chapter 3 reports our original research assessing the relationships between CBF and amyloid beta and tau aggregation measured with PET, as well as whether hypertension or APOEε4 positivity affects these relationships, in older adults without dementia from the IADRC. Chapter 4 reports our original research assessing the relationship between the spatial distribution of tau and subjective memory concerns. / 2023-05-24

Lithium is widely used in the management of bipolar disorder, yet memory impairment is a serious side effect. To assess the effects of lithium on spatial working and reference memories, we have employed a plus maze utilizing spontaneous alternation (SA) and place-learning paradigms in two experiments with the black molly fish. Four treatment groups were gavaged with 20 μl of a 10, 100, or 1000 mM lithium chloride (LiCl) solution or ddH2O vehicle every 12 h for 22 to 24 days. On Day 15, subjects began an 8-day SA task or a 10-day place-learning task. Results indicate that there is a significant difference in SA performance among the treatment groups for Days 1, 2, and 3. Results of the place-learning task indicate that the 1 M dose group needed significantly more trials to reach criterion and made significantly fewer correct first choices than the other dose groups. Capillary ion analysis determinations of plasma and brain lithium levels illustrate linear dose-response relationships to doses administered. Regression analyses indicate that there is a relationship between SA performance and plasma/brain lithium levels during the initial part of testing. Collectively, the results indicate that chronic lithium administration impairs spatial working and reference memories.

Background: Inflammation is proposed to play a role in the development of Alzheimer's disease, and may also be involved in the pathogenesis of mild cognitive impairment (MCI). This study examined the association of inflammatory markers in serum or plasma with prevalent MCI and MCI subtypes in a population-based sample. Methods: Olmsted County, MN, residents aged 70-89 years on October 1, 2004, were evaluated using the Clinical Dementia Rating Scale, a neurological evaluation, and neuropsychological testing. Information ascertained for each participant was reviewed by an expert panel of neuropsychologists, physicians, and nurses, and a diagnosis of normal cognition, MCI, or dementia was made by consensus. C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis alpha (TNFα), and adiponectin were measured at baseline. Results: Among 313 subjects with MCI and 1570 cognitively normal subjects, a CRP level in the upper quartile (>3.3 mg/L) was significantly associated with MCI (odds ratio [OR], 1.42; 95% confidence interval [CI], 1.00-2.01) and with nonamnestic MCI (OR, 2.05; 95% CI, 1.12-3.78) after adjusting for age, sex, and years of education. However, there was no association with amnestic MCI (OR, 1.21; 95% CI, 0.81-1.82). No association was observed with the other inflammatory markers. Conclusions: Plasma CRP is associated with prevalent MCI and with nonamnestic MCI in elderly, nondemented persons in a population-based setting. These findings suggest the involvement of inflammation in the pathogenesis of MCI.

Background: The objective of this study was to establish a prospective population-based cohort to investigate the prevalence, incidence and risk factors for mild cognitive impairment (MCI) and dementia. Methods: The Olmsted County, Minn., population, aged 70-89 years on October 1, 2004, was enumerated using the Rochester Epidemiology Project. Eligible subjects were randomly selected and invited to participate. Participants underwent a comprehensive in-person evaluation including the Clinical Dementia Rating Scale, a neurological evaluation and neuropsychological testing. A consensus diagnosis of normal cognition, MCI or dementia was made by a panel using previously published criteria. A subsample of subjects was studied via telephone interview. Results: Four hundred and two subjects with dementia were identified from a detailed review of their medical records but were not contacted. At baseline, we successfully evaluated 703 women aged 70-79 years, 769 women aged 80-89 years, 730 men aged 70-79 years and 517 men aged 80-89 years (total n = 2,719). Among the participants, 2,050 subjects were evaluated in person and 669 via telephone. Conclusions: Strengths of the study are that the subjects were randomly selected from a defined population, the majority of the subjects were examined in person, and MCI was defined using published criteria. Here, we report the design and sampling, participation, baseline measures and sample characteristics.

Background For the 1.2 million older adults residing in U.S. nursing homes, little is known about their experience with physical frailty and cognitive impairment, two critical interrelated aging conditions. Methods Minimum Data Set 3.0 was used. Physical frailty was measured by FRAIL-NH and cognitive impairment by Brief Interview for Mental Status and Cognitive Performance Scale. Demographic and clinical characteristics were adjusted accordingly. Aim 1 described the prevalence of physical frailty and cognitive impairment and longitudinally examined the association between two conditions with the non-proportional odds model. Aim 2 used latent class analysis to identify physical frailty subgroups and estimated their association with cognitive impairment using multinomial logistic regression. Aim 3 fitted group-based trajectory models to identify physical frailty trajectories and cognitive impairment trajectories and quantified the association between the two sets of trajectories. Main Results Around 60% of older residents were physically frail and 68% had moderate/severe cognitive impairment, with improvement and worsening observed in both conditions, particularly in the first three months. Older residents with moderate/severe cognitive impairment were consistently and increasingly more likely to be frail. Three physical frailty subgroups were identified at admission. Greater cognitive impairment was associated with higher odds to belong to “severe physical frailty”. Five physical frailty trajectories and three cognitive impairment trajectories were identified over the first six months. One in five older residents were “Consistently Frail” and “Consistently Severe Cognitive Impairment”. Conclusion Findings emphasized the need for care management tailored to the heterogeneous presentations and progression trajectories of physical frailty and cognitive impairment.

Cognitive impairment is commonly seen in the elderly population. It is unclear if cognitive deficit in heart failure (HF) patients is a primary factor for higher hospital readmission rates in this population. The Centers for Medicare and Medicaid Services have established strict guidelines for reimbursement on readmissions that occur within 30 days. It is imperative that organizations identify and rectify issues that impact readmissions. The aim of this project was to determine if there is a reduction in HF readmission after patients are screened for cognitive impairment. Orem's self-care model guided the project by providing a framework of inquiry regarding the impact of cognitive impairment on self-care deficits and the need for support for persons with heart failure. The project examined the hospital's 30-day readmission rate for the HF patients who received cognitive screening using a chi-square test; this analysis excluded HF patients who were not screened for cognitive impairment. Readmission rates for all patients during a 6-month period were examined. Two hundred sixty-eight patient records were reviewed; 48 patients were readmitted, and of those, 28 patients had completed the cognitive assessment, meeting the criteria for the project. The change in readmission rates was not significant (p = 0.196), suggesting that cognitive screening of patients is not associated with reduced readmission rates. Further research should examine the role of cognitive screening in addition to other resources on the 30-day readmission rate of HF patients. Social change will be improved as a result of the improved quality of life for HF patients and the reduced per-capita cost of health care in the United States.