Traumatic brain injury alters the effects of class II invariant peptide (CLIP) antagonism on chronic meningeal CLIP + B cells, neuropathology, and neurobehavioral impairment in 5xFAD mice.

BACKGROUND: Traumatic brain injury (TBI) is a significant risk factor for Alzheimer's disease (AD), and accumulating evidence supports a role for adaptive immune B and T cells in both TBI and AD pathogenesis. We previously identified B cell and major histocompatibility complex class II (MHCII)-associated invariant chain peptide (CLIP)-positive B cell expansion after TBI. We also showed that antagonizing CLIP binding to the antigen presenting groove of MHCII after TBI acutely reduced CLIP + splenic B cells and was neuroprotective. The current study investigated the chronic effects of antagonizing CLIP in the 5xFAD Alzheimer's mouse model, with and without TBI. METHODS: 12-week-old male wild type (WT) and 5xFAD mice were administered either CLIP antagonist peptide (CAP) or vehicle, once at 30 min after either sham or a lateral fluid percussion injury (FPI). Analyses included flow cytometric analysis of immune cells in dural meninges and spleen, histopathological analysis of the brain, magnetic resonance diffusion tensor imaging, cerebrovascular analysis, and assessment of motor and neurobehavioral function over the ensuing 6 months. RESULTS: 9-month-old 5xFAD mice had significantly more CLIP + B cells in the meninges compared to age-matched WT mice. A one-time treatment with CAP significantly reduced this population in 5xFAD mice. Importantly, CAP also improved some of the immune, histopathological, and neurobehavioral impairments in 5xFAD mice over the ensuing six months. Although FPI did not further elevate meningeal CLIP + B cells, it did negate the ability of CAP to reduce meningeal CLIP + B cells in the 5xFAD mice. FPI at 3 months of age exacerbated some aspects of AD pathology in 5xFAD mice, including further reducing hippocampal neurogenesis, increasing plaque deposition in CA3, altering microgliosis, and disrupting the cerebrovascular structure. CAP treatment after injury ameliorated some but not all of these FPI effects.

Using smartphone technology to improve prospective memory functioning: A randomized controlled trial.

BACKGROUND: A decline in the ability to perform daily intentions-known as prospective memory-is a key driver of everyday functional impairment in dementia. In the absence of effective pharmacological treatments, there is a need for developing, testing, and optimizing behavioral interventions that can bolster daily prospective memory functioning. We investigated the feasibility and efficacy of smartphone-based strategies for prospective memory in persons with cognitive impairment. METHODS: Fifty-two older adults (74.79 ± 7.20 years) meeting diagnostic criteria for mild cognitive impairment or mild dementia were enrolled in a 4-week randomized controlled trial. Participants were trained to use a digital voice recorder app or a reminder app to off-load prospective memory intentions. Prospective memory was assessed using experimenter-assigned tasks (e.g., call the laboratory on assigned days), standardized questionnaires, and structured interviews. Secondary dependent measures included days of phone and app usage, acceptability ratings, quality of life, and independent activities of daily living. RESULTS: Participant ratings indicated that the intervention was acceptable and feasible. Furthermore, after the four-week intervention, participants reported improvements in daily prospective memory functioning on standardized questionnaires (p < 0.001, ηp2  = 0.285) and the structured interview (p < 0.001, d = 1.75). Participants performed relatively well on experimenter-assigned prospective memory tasks (51.7% ± 27.8%), with performance levels favoring the reminder app in Week 1, but reversing to favor the digital recorder app in Week 4 (p = 0.010, ηp2  = 0.079). Correlational analyses indicated that greater usage of the digital recorder or reminder app was associated with better prospective memory performance and greater improvements in instrumental activities of daily living (completed by care partners), even when controlling for condition, age, baseline cognitive functioning, and baseline smartphone experience. CONCLUSIONS: Older adults with cognitive disorders can learn smartphone-based memory strategies and doing so benefits prospective memory functioning and independence.

Apathy and actions- another consideration when theorizing about embodied nature of language in Parkinson's disease.

Objectives Individuals with Parkinson's disease (PD) have difficulty processing actions or verbs relative to nouns. Verb difficulties are thought to represent the coupling of language and motor networks. However, those with PD also frequently experience apathy. The overlap between apathy and action language difficulties is to date unexplored. Furthermore, whether verb/action fluency difficulty represents verb degradation (semantic/conceptual) or a selective lexical retrieval difficulty has not been determined. Methods In the current study, 20 individuals with PD without dementia completed cued action (verb) and animal (noun) fluency tasks in addition to assessments of apathy, cognition, and motor functioning. Results Individuals who exhibited impairments on action and animal fluency improved around 50% with the provision of cueing. The degree to which action fluency improved with cueing was correlated with behavioral/initiation apathy (rs=.56) as well as motor dysfunction (rs=-.57), while no similar relationship was found between those factors and nouns. Conclusions These findings suggest that impaired retrieval of actions and nouns are present in PD, but may have different underlying neuropsychological underpinnings. This provides preliminary support for grounded cognition models, which suggest the brain organizes information around motor, perceptual, and other networks. MESH terms Parkinson Disease, Neurocognitive Disorders, Apathy, Language Disorders, Neuropsychological Tests, Cognition.

Normative Data for Derived Measures and Discrepancy Scores for the Uniform Data Set 3.0 Neuropsychological Battery.

OBJECTIVE: The Uniform Data Set 3.0 (UDS 3.0) neuropsychological battery is a recently published battery intended for clinical research with older adult populations. While normative data for the core measures has been published, several additional discrepancy and derived scores can also be calculated. We present normative data for Trail Making Test (TMT) A & B discrepancy and ratio scores, semantic and phonemic fluency discrepancy scores, Craft Story percent retention score, Benson Figure percent retention score, difference between verbal and visual percent retention, and an error index. METHOD: Cross-Sectional data from 1803 English speaking, cognitively normal control participants were obtained from the NACC central data repository. RESULTS: Descriptive information for derived indices is presented. Demographic variables, most commonly age, demonstrated small but significant associations with the measures. Regression values were used to create a normative calculator, made available in a downloadable supplement. Statistically abnormal values (i.e., raw scores corresponding to the 5th, 10th, 90th, and 95th percentiles) were calculated to assist in practical application of normative findings to individual cases. Preliminary validity of the indices are demonstrated by a case study and group comparisons between a sample of individuals with Alzheimer's (N = 81) and Dementia with Lewy Bodies (DLB; N = 100). CONCLUSIONS: Clinically useful normative data of such derived indices from the UDS 3.0 neuropsychological battery are presented to help researchers and clinicians interpret these scores, accounting for demographic factors. Preliminary validity data is presented as well along with limitations and future directions.