Delayed and More Variable Unimanual and Bimanual Finger Tapping in Alzheimer's Disease: Associations with Biomarkers and Applications for Classification.

BACKGROUND: Despite reports of gross motor problems in mild cognitive impairment (MCI) and Alzheimer's disease (AD), fine motor function has been relatively understudied. OBJECTIVE: We examined if finger tapping is affected in AD, related to AD biomarkers, and able to classify MCI or AD. METHODS: Forty-seven cognitively normal, 27 amnestic MCI, and 26 AD subjects completed unimanual and bimanual computerized tapping tests. We tested 1) group differences in tapping with permutation models; 2) associations between tapping and biomarkers (PET amyloid-ß, hippocampal volume, and APOEɛ4 alleles) with linear regression; and 3) the predictive value of tapping for group classification using machine learning. RESULTS: AD subjects had slower reaction time and larger speed variability than controls during all tapping conditions, except for dual tapping. MCI subjects performed worse than controls on reaction time and speed variability for dual and non-dominant hand tapping. Tapping speed and variability were related to hippocampal volume, but not to amyloid-ß deposition or APOEɛ4 alleles. Random forest classification (overall accuracy = 70%) discriminated control and AD subjects, but poorly discriminated MCI from controls or AD. CONCLUSIONS: MCI and AD are linked to more variable finger tapping with slower reaction time. Associations between finger tapping and hippocampal volume, but not amyloidosis, suggest that tapping deficits are related to neuropathology that presents later during the disease. Considering that tapping performance is able to differentiate between control and AD subjects, it can offer a cost-efficient tool for augmenting existing AD biomarkers.

Rationale and study protocol for We-PAP: a randomized pilot/feasibility trial of a couples-based intervention to promote PAP adherence and sleep health compared to an educational control.

BACKGROUND: Obstructive sleep apnea (OSA) is a serious health condition that affects approximately 30-50% of older adults and contributes to risk for cardiometabolic disorders and dementia. Despite the well-documented role of partners in treatment seeking and adherence to positive airway pressure (PAP), treatments for OSA have nearly exclusively focused on the patient and current treatments for OSA do not address co-existing sleep problems such as insomnia that are prevalent in both patients with OSA and their partners. Therefore, the goal of this study is to develop and test a novel couples-based sleep health intervention to promote adherence to PAP and improve sleep health of the couple. METHODS: We are conducting a two-arm, parallel group, single blind, randomized controlled pilot/feasibility trial to compare our novel couples-based sleep health intervention (We-PAP) to an information control group (IC). We-PAP is based on a transdiagnostic model and uses a dyadic approach including increasing effective partner support, communication skills, and couple-level goal-setting. We-PAP involves 3 sessions and delivered via telehealth in weekly sessions. The IC includes standardized patient educational materials. Both groups receive the usual follow-up with their medical team. The study involves assessments at pre-treatment, post-intervention (approximately 1 month after starting PAP and completing We-PAP sessions or IC) and 3 months after starting PAP. Our main outcomes are feasibility and acceptability ratings. Secondary outcomes include comparing We-PAP to IC for PAP adherence, sleep quality (self-report and objective) and cognitive measures. DISCUSSION: We-PAP is the first couples-based transdiagnostic sleep health intervention for patients with OSA and their partners. Results of this study will be used to inform the design of a subsequent fully powered clinical trial. If successful, this intervention could significantly advance current clinical practice in the treatment of OSA and sleep health more comprehensively in older adults. Moreover, this intervention may be useful for improving sleep in other aging populations with multiple sleep and other health problems, including patients with chronic illnesses or those at risk for Alzheimer's disease and their caregivers. TRIAL REGISTRATION: NCT04759157 . Date of registration: February 8, 2021. URL of trial registry record.

Evaluating the Impact of Cochlear Implantation on Cognitive Function in Older Adults.

OBJECTIVES/HYPOTHESIS: We hypothesize that treating hearing loss through cochlear implantation in older adults will improve cognitive function. STUDY DESIGN: Prospective, interventional study. METHODS: Thirty-seven participants aged 65 years and older who met criteria for cochlear implantation were enrolled. Subjects underwent preoperative cognitive testing with a novel arrangement of standard neuropsychological tests, including tests of general cognition and mood (Mini-Mental Status Exam [MMSE]), tests of verbally based stimuli and responses (Digit Span, Stroop, Hopkins Verbal Learning Test-Revised [HVLT-R], Hayling Sentence Completion), and comparable visually based tests (Spatial Span, d2 Test of Attention, Brief Visuospatial Memory Test [BVMT], Trails A and B). Testing was repeated 12 months postoperatively. RESULTS: One year postoperatively, subjects showed a statistically significant improvement in hearing and on the following tests of cognitive function: concentration performance of the d2 Test of Attention, Hayling Sentence Completion Test, HVLT-R (total and delayed recall), Spatial Span (backward), and Stroop Color Word Test. A subgroup analysis was performed comparing 13 participants with preoperative cognitive impairment (MMSE ≤ 24) to 24 participants with normal cognition (MMSE ≥ 25). In this subgroup analysis, a greater magnitude of improvement was seen in those with impaired cognition, with statistically significant improvement in Digit Span (scaled score), Stroop Word (T-score), Stroop Color-Word (residual and T-score), HVLT-R, and Hayling (overall). All verbally based test scores improved, and 75% of the visually based test scores improved. CONCLUSIONS: This study demonstrates the cognitive benefits of cochlear implantation in older adults 1 year after surgery. For older adults with cognitive impairment prior to cochlear implantation, the cognitive benefits were even greater than in subjects with normal cognition. LEVEL OF EVIDENCE: 3, nonrandomized controlled cohort Laryngoscope, 132:S1-S15, 2022.

Predictors of cognitive decline in a multi-racial sample of midlife women: A longitudinal study.

Objective: Hypertension, diabetes, depressive symptoms, and smoking are predictors of cognitive decline in late life. It is unknown if these risk factors are associated with cognition during midlife or if the associations between these risk factors and cognition vary by race. This longitudinal study examined (a) risk factors for decline in episodic memory, processing speed, and working memory in midlife women and (b) if the associations between risk factors and cognitive decline were moderated by race. Method: Participants (aged 42-52) were European American (n = 1,000), African American (n = 516), and Asian American (n = 437) women from the Study of Women's Health Across the Nation. Two-level hierarchical linear models tested risk factors, race, and their interactions as predictors of cognitive change over time. Results: African Americans had poorer baseline episodic memory, processing speed, and working memory and greater episodic memory decline compared to European Americans. Asian Americans had poorer episodic memory and working memory, but better processing speed than European Americans. Depressive symptoms were associated with poorer episodic memory and processing speed at baseline; further, diabetes was associated with poorer processing speed at baseline. Greater depressive symptoms were associated with poorer episodic memory at baseline for African Americans but not European Americans. Conclusions: Our study results highlight racial disparities in cognition during midlife. Depressive symptoms may be particularly detrimental to the cognitive health of African Americans. Clinical and public health interventions for healthy cognitive aging should be tailored to the unique risks of racial groups. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Short-term practice effects in mild cognitive impairment: Evaluating different methods of change.

Practice effects are improvements on cognitive tests as a result of repeated exposure to testing material. However, variability exists in the literature about whether patients with amnestic mild cognitive impairment (MCI) display practice effects, which may be partially due to the methods used to calculate these changes on repeated tests. The purpose of the current study was to examine multiple methods of assessing short-term practice effects in 58 older adults with MCI. The cognitive battery, which included tests of memory (Hopkins Verbal Learning Test-Revised and Brief Visuospatial Memory Test-Revised) and processing speed (Symbol Digit Modalities Test and Trail Making Test Parts A and B), was administered twice across one week. Dependent t tests showed statistically significant improvement on memory scores (ps < .01, ds = 0.8-1.3), but not on processing speed scores. Despite this, the sample showed no clinically meaningful improvement on any cognitive scores using three different reliable change indices. Regression-based change scores did identify relatively large groups of participants who showed smaller than expected practice effects, which may indicate that this method is more sensitive in identifying individuals who may portend a declining trajectory. Practice effects remain a complex construct, worthy of continued investigation in diverse clinical conditions.

Cognitive Predictors of Reasoning through Treatment Decisions in Patients with Newly Diagnosed Brain Metastases.

To examine the association between reasoning through medical treatment decisions and cognition in a sample of patients with brain metastasis. The association between reasoning and cognition was examined using data from 41 patients with diagnosed brain metastasis. All diagnoses were made by a board-certified radiation oncologist and were verified histologically. In total, 41 demographically matched, cognitively healthy controls were also included to aid in classifying patients with brain metastasis according to reasoning status (i.e., intact or impaired). Results indicate that measures of episodic memory and processing speed were associated with reasoning. Using these two predictors, actuarial equations were constructed that can be used to help screen for impaired reasoning ability in patients' with brain metastasis. The equations presented in this study have clinical significance as they can be used to help identify patients at risk for possessing a diminished ability to reason through medical treatment decisions and, thus, are in need of a more comprehensive evaluation of their medical decision-making capacity.

Cognitive predictors of understanding treatment decisions in patients with newly diagnosed brain metastasis.

BACKGROUND: Medical decision-making capacity is a higher-order functional skill that refers to a patient's ability to make informed, sound decisions related to care and treatment. In a medical context, understanding is the most cognitively demanding consent standard and refers to a patient's ability to comprehend information to the extent that informed decisions can be made. METHODS: The association between reasoning and cognition was examined using data from 41 patients with diagnosed brain metastasis. All diagnoses were made by a board-certified radiation oncologist and were verified histologically. In total, 41 demographically matched, cognitively healthy controls were also included to aid in classifying patients with brain metastasis according to reasoning status (ie, intact or impaired). RESULTS: Results indicate that measures of simple attention, verbal fluency, verbal memory, processing speed, and executive functioning were all associated with understanding, and that verbal memory and phonemic fluency were the primary cognitive predictors. Using these two primary predictors, equations can be constructed to predict the ability to understand treatment decisions in patients with brain metastasis. CONCLUSIONS: Although preliminary, these data demonstrate how cognitive measures can estimate understanding as it relates to medical decision-making capacities in these patients. Clinically, these findings suggest that poor verbal memory and expressive language function could serve as "red flags" for reduced consent capacity in this patient population, thus signaling that a more comprehensive medical decision-making capacity evaluation is warranted.

Practice effects and amyloid deposition: preliminary data on a method for enriching samples in clinical trials.

Clinical trials in Alzheimer disease are moving toward prevention studies in prodromal individuals with amyloid burden. However, methods are needed to identify individuals expected to be amyloid positive for these studies to be feasible and cost-effective. The current study sought to determine whether short-term practice effects on cognitive tests can identify those with notable uptake on amyloid imaging. Twenty-five, nondemented older adults (15 cognitively intact, 10 with mild cognitive impairment) underwent amyloid imaging through F-flutemetamol and 2 cognitive testing sessions across 1 week to determine practice effects on a visual memory test. Results indicated that, whereas F-flutemetamol uptake showed little association with baseline performance on a visual memory test (r=-0.04, P=0.85), it was significantly correlated with practice effects across 1 week on that same memory measure (r=-0.45, P=0.02), with greater uptake being associated with lower practice effects. The odds ratio of notable F-flutemetamol uptake was 5 times higher in individuals with low practice effects compared with high practice effects. Although these preliminary results need to be replicated in larger samples, short-term practice effects on cognitive tests may provide an affordable screening method to identify individuals who are amyloid positive, which could enrich samples for preventative clinical trials in Alzheimer disease.

Assessing reliable change using the repeatable battery for the assessment of neuropsychological status (RBANS) for patients with Parkinson's Disease undergoing deep brain stimulation (DBS) surgery.

Parkinson's disease (PD) is progressive neurological disease characterized by resting tremor, rigidity, akinesia, postural instability and cognitive changes. The symptoms of PD are debilitating and often become unsatisfactorily treated by medication. Deep brain stimulation (DBS) is an effective treatment to significantly reduce the cardinal motor symptoms of PD. However, the neuropsychological effects of this treatment are less clear. This study examined pre- to post-DBS scores on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) using Reliable Change Indices (RCIs) derived from 20 patients with PD who were medically managed, and then compared to 20 patients with PD treated with DBS and medication. When using group statistical analyses and false discovery rate correction, no significant differences between or within groups were evident at baseline or at follow-up. However, when using the RCIs more patients in the DBS group exhibited reliable change in RBANS scores than did the Med Tx group. Although preliminary, these RCIs provide clinicians and researchers a foundational tool for assessing the effects of interventions (e.g., DBS) independent of the effects of PD and measurement error when using the RBANS.

The neuropsychological course of acute delirium in adult hematopoietic stem cell transplantation patients.

Although delirium is a common medical comorbidity with altered cognition as its defining feature, few publications have addressed the neuropsychological prodrome, profile, and recovery of patients tested during delirium. We characterize neuropsychological performance in 54 hemapoietic stem cell/bone marrow transplantation (BMT) patients shortly before, during, and after delirium and in BMT patients without delirium and 10 healthy adults. Patients were assessed prospectively before and after transplantation using a brief battery. BMT patients with delirium performed more poorly than comparisons and those without delirium on cross-sectional and trend analyses. Deficits were in expected areas of attention and memory, but also in psychomotor speed and learning. The patients with delirium did not return to normative "average" on any test during observation. Most tests showed a mild decline in the visit before delirium, a sharp decline with delirium onset, and variable performance in the following days. This study adds to the few investigations of neuropsychological performance surrounding delirium and provides targets for monitoring and early detection; Trails A and B, RBANS Coding, and List Recall may be useful for delirium assessment.

Cognitive change on the repeatable battery of neuropsychological status (RBANS) in Parkinson's disease with and without bilateral subthalamic nucleus deep brain stimulation surgery.

Cognitive change following bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) surgery in those with Parkinson's disease (PD) has led to equivocal results. The current study applied a standardized regression-based (SRB) method based on 20 medically managed PD patients and 20 STN DBS PD surgical patients who were administered the Repeatable Battery of Neuropsychological Status (RBANS). Of the medically managed PD participants, 94% remained stable compared to 73% of the DBS group. In the DBS group cognitive change was noted on the Total scale and the Immediate Memory Index. A secondary analysis also revealed reliable change on several subtest scores. Although preliminary, the current study provides change parameters for post DBS surgery on this brief battery.

Medical burden and cognition in older patients in primary care: selective deficits in attention.

Cognitive deficits have been associated with several chronic medical conditions, but the additive effects of multiple conditions on cognition have less studied. Six hundred ninety-two community dwelling older adults were enrolled through their primary care physicians and evaluated for medical burden and cognition. Medical burden was assessed by self-report questionnaire. Cognition was assessed with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). After adjusting for age and gender, there was a strong inverse relationship between medical burden and cognition, with individuals with more medical comorbidities performing worse on cognitive measures. Attention was selectively poor, especially for a speeded, divided attention task, in patients with five or more comorbid medical conditions. These findings could have clinical implications, as poorer attention, especially in patients with multiple medical problems, could lead to poorer medical compliance and worse outcomes.

Neuropsychological and psychiatric functioning pre- and posthematopoietic stem cell transplantation in adult cancer patients: a preliminary study.

The current study characterizes cognitive and psychiatric status in hematopoietic stem cell transplantation (HSCT) patients shortly before and after transplant. Thirty adult patients were assessed prospectively 1-2 weeks before transplantation and 100 days posttransplantation on neuropsychological and psychiatric measures. Before transplant, participants showed mild impairments on several neuropsychological measures, with the poorest performances occurring on learning and attention. Psychiatric functioning was significantly elevated compared with normative data. Significant improvements, however, were observed on neuropsychological measures by 100 days after transplant. Depression and anxiety scores also improved. Candidates for HSCT experienced mild diffuse cognitive dysfunction and psychiatric morbidity before the procedure, but these symptoms significantly improved by 3 months following their transplant in this small sample. Education about these possible pretransplant sequelae and the potential for rebound may be helpful to patients and families as they prepare for this treatment and the recovery period.

Test performance and classification statistics for the Rey Auditory Verbal Learning Test in selected clinical samples.

The Rey Auditory Verbal Learning Test [RAVLT; Rey, A. (1941). L'examen psychologique dans les cas d'encéphalopathie traumatique. Archives de Psychologie, 28, 21] is a commonly used neuropsychological measure that assesses verbal learning and memory. Normative data have been compiled [Schmidt, M. (1996). Rey Auditory and Verbal Learning Test: A handbook. Los Angeles, CA: Western Psychological Services]. When assessing an individual suspected of neurological dysfunction, useful comparisons include the extent that the patient deviates from healthy peers and also how closely the subject's performance matches those with known brain injury. This study provides the means and S.D.'s of 392 individuals with documented neurological dysfunction [closed head TBI (n=68), neoplasms (n=57), stroke (n=47), Dementia of the Alzheimer's type (n=158), and presurgical epilepsy left seizure focus (n=28), presurgical epilepsy right seizure focus (n=34)] and 122 patients with no known neurological dysfunction and psychiatric complaints. Patients were stratified into three age groups, 16-35, 36-59, and 60-88. Data were provided for trials I-V, List B, immediate recall, 30-min delayed recall, and recognition. Classification characteristics of the RAVLT using [Schmidt, M. (1996). Rey Auditory and Verbal Learning Test: A handbook. Los Angeles, CA: Western Psychological Services] meta-norms found the RAVLT to best distinguish patients suspected of Alzheimer's disease from the psychiatric comparison group.

Incidence of delirium and associated mortality in hematopoietic stem cell transplantation patients.

Delirium has been associated with a high risk of mortality in medical patients. Despite the high incidence of delirium in patients who undergo hemapoietic stem cell transplantation (HSCT), delirium as a risk factor for death has not been examined in this population. Thirty adult patients undergoing HSCT who were admitted to the University of Iowa Blood and Marrow Transplantation Program inpatient unit were assessed prospectively from 1 to 2 weeks before transplantation, throughout their inpatient stay, and at 100 days after transplantation. The Delirium Rating Scale and Memorial Delirium Assessment Scale were used twice weekly during the inpatient period to assess delirium severity and occurence. Patients' self-reports of medical history, computerized medical records, and neuropsychological and psychiatric assessments were used to identify pretransplantation risk factors. The incidence of delirium (Delirium Rating Scale score >12 or Memorial Delirium Assessment Scale score >or=8) was 43% and occurred with highest frequency in the first 2 weeks after transplantion. The presence of delirium at any point during hospitalization after transplantation and transplant type (allogeneic) were highly predictive of mortality (p < .0005; odds ratios, 14.0 and 14.4). In conclusion, this study highlights the importance of monitoring for delirium during the acute recovery period after transplantation and suggests that early or even prophylactic treatment for delirium should be studied. Studies to determine the factors that connect delerium soon after transplantation to mortality are highly warranted.