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We sought to determine whether the biomarkers of chronic inflammation predict cognitive decline in a prospective observational study. We measured baseline serum soluble urokinase plasminogen activator receptor (suPAR) and high sensitivity C-reactive protein (hs-CRP) levels in 282 participants of the University of Michigan Memory and Aging Project. Cognitive function was measured using the Montreal Cognitive Assessment (MoCA) and the Clinical Dementia Rating (CDR) scale for up to five time points. SuPAR and hs-CRP levels were not significantly higher in participants with mild cognitive impairment ( n  = 97) or dementia ( n  = 59), compared to those with normal cognitive function ( n  = 126). Overall, 14% of participants experienced significant cognitive decline over the study period. The change in MoCA or CDR scores over time did not differ significantly according to baseline suPAR or hs-CRP levels. Chronic systemic inflammation, as measured by serum suPAR or hs-CRP levels, is unlikely to contribute significantly to cognitive decline., Competing Interests: SSH is a member of the scientific advisory board of Walden Biosciences. Other authors do not have a conflict of interest. Author disclosures are available in the supporting information., (© 2024 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Introduction: This study assessed the construct validity and clinical utility of the National Alzheimer's Coordinating Center Lewy Body Dementia (LBD) Module, consisting of the Speeded Attention and Noise Pareidolia Tasks., Methods: Participants included 459 older adults diagnosed as cognitively normal (n = 202), or with non-amnestic mild cognitive impairment (n = 61), amnestic mild cognitive impairment (n = 96), Alzheimer's disease dementia (n = 44), or LBD (n = 56)., Results: Speeded Attention demonstrated strong convergent validity and moderate discriminant validity when compared to established neuropsychological tests. Noise Pareidolia demonstrated strong discriminant validity, but limited convergent validity. Noise Pareidolia scores were significantly lower in those with reported hallucinations, delusions, or REM sleep behavior disorder symptoms. LBD Module tests discriminated well between cognitively normal adults and those with LBD., Discussion: The LBD Module demonstrates promising construct validity and clinical utility, which support its use across research and clinical settings., Competing Interests: None., (© 2021 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association.)

Introduction: Mnemonic strategy training (MST) has been shown to improve cognitive performance and increase brain activation in those with mild cognitive impairment (MCI). However, little is known regarding the effects of MST on functional connectivity (FC) at rest. The aim of the present study was to investigate the MST focused on face-name associations effect on resting-state FC in those with MCI., Methods: Twenty-six amnestic MCI participants were randomized in MST (N = 14) and Education Program (active control; N = 12). Interventions occurred twice a week over two consecutive weeks (ie, four sessions). Resting-state functional magnetic resonance imaging was collected at pre- and post-intervention. Regions of interest (ROIs) were selected based on areas that previously showed task-related activation changes after MST. Changes were examined through ROI-to-ROI analysis and significant results were corrected for multiple comparisons., Results: At post-intervention, only the MST group showed increased FC, whereas the control group showed decreased or no change in FC. After MST, there was an increased FC between the left middle temporal gyrus and right orbitofrontal cortex. In addition, a time-by-group interaction indicated that the MST group showed greater increased FC between the right inferior frontal gyrus and left brain regions, such as fusiform gyrus, temporal pole, and orbitofrontal cortex relative to controls., Discussion: MST enhanced FC in regions that are functionally relevant for the training; however, not in all ROIs investigated. Our findings suggest that MST-induced changes are reflected in task-specific conditions, as previously reported, but also in general innate connectivity. Our results both enhance knowledge about the mechanisms underlying MST effects and may provide neurophysiological evidence of training transfer., Competing Interests: No author has any conflict of interest., (© 2020 The Authors. Alzheimer's & Dementia: Translational Research & Clinical Interventions published by Wiley Periodicals, Inc. on behalf of Alzheimer's Association.)

Introduction: Cognitive decline and dementia significantly affect independence and quality of life in older adults; therefore, it is critical to identify effective cognition-oriented treatments (COTs; eg, cognitive training, rehabilitation) that can help maintain or enhance cognitive functioning in older adults, as well as reduce dementia risk or alleviate symptoms associated with pathological processes., Methods: The Cognitive Intervention Design Evaluation and Reporting (CIDER), a working group from the Non-Pharmacological Interventions Professional Interest Area (NPI-PIA) of the Alzheimer's Association conducted as survey in 2017 with experts in COTs worldwide. The survey's aims were three-fold: (1) determine the common attitudes, beliefs, and practices of experts involved in the COTs research targeting older people; (2) identify areas of relative agreement and disagreement among experts in the field; and (3) offer a critical review of the literature, including recommendations for future research., Results: The survey identified several areas of agreements among experts on critical features of COTs, and on study design and outcome measures. Nevertheless, there were some areas with relative disagreement. Critically, expert opinions were not always supported by scientific evidence, suggesting that methodologic improvements are needed regarding design, implementation, and reporting of COTs. There was a clear consensus that COTs provide benefits and should be offered to cognitively unimpaired older adults, mild cognitive impairment (MCI), and mild dementia, but opinions differed for moderate and severe dementia. In addition, there is no consensus on the potential role of COTs in dementia prevention, indicating that future research should prioritize this aspect., Discussion: Evidence of COTs in older adults is encouraging, but additional evidence is needed to enhance dementia prevention. Consensus building and guidelines in the field are critical to improve and accelerate the development of high-quality evidence for COTs in cognitively unimpaired older adults, and those with MCI and dementia., Competing Interests: The authors declare no conflict of interest, (© 2020 The Authors. Alzheimer's & Dementia: Translational Research & Clinical Interventions published by Wiley Periodicals, Inc. on behalf of Alzheimer's Association.)

Introduction: We present findings of a novel and ecologically relevant associative memory test, the Object Location Touchscreen Test (OLTT), which was posited as sensitive to early medial temporal lobe compromise associated with mild cognitive impairment (MCI)., Methods: A total of 114 participants, including healthy young and older controls and patients with MCI, completed the OLTT and standard neuropsychological testing. The OLTT required participants to recall the location of objects under free and cued recall conditions, with accuracy evaluated using distance measures (i.e., a continuous error score), and a standard recognition format. Correlations between performance and volumetric data were evaluated from a subset of 77 participants., Results: Significant age effects were dwarfed by MCI effects across all test conditions. OLTT Cued Recall was strongly and specifically related to the volume of disease-relevant medial temporal lobe regions, generally more than traditional memory tests., Discussion: The OLTT may be sensitive to early structural compromise in regions affected by Alzheimer's disease.

Introduction: Memory deficits characterize Alzheimer's dementia and the clinical precursor stage known as mild cognitive impairment. Nonpharmacologic interventions hold promise for enhancing functioning in these patients, potentially delaying functional impairment that denotes transition to dementia. Previous findings revealed that mnemonic strategy training (MST) enhances long-term retention of trained stimuli and is accompanied by increased blood oxygen level-dependent signal in the lateral frontal and parietal cortices as well as in the hippocampus. The present study was designed to enhance MST generalization, and the range of patients who benefit, via concurrent delivery of transcranial direct current stimulation (tDCS)., Methods: This protocol describes a prospective, randomized controlled, four-arm, double-blind study targeting memory deficits in those with mild cognitive impairment. Once randomized, participants complete five consecutive daily sessions in which they receive either active or sham high definition tDCS over the left lateral prefrontal cortex, a region known to be important for successful memory encoding and that has been engaged by MST. High definition tDCS (active or sham) will be combined with either MST or autobiographical memory recall (comparable to reminiscence therapy). Participants undergo memory testing using ecologically relevant measures and functional magnetic resonance imaging before and after these treatment sessions as well as at a 3-month follow-up. Primary outcome measures include face-name and object-location association tasks. Secondary outcome measures include self-report of memory abilities as well as a spatial navigation task (near transfer) and prose memory (medication instructions; far transfer). Changes in functional magnetic resonance imaging will be evaluated during both task performance and the resting-state using activation and connectivity analyses., Discussion: The results will provide important information about the efficacy of cognitive and neuromodulatory techniques as well as the synergistic interaction between these promising approaches. Exploratory results will examine patient characteristics that affect treatment efficacy, thereby identifying those most appropriate for intervention.

Introduction: The current study examined the relationship between subjective memory complaints (both self- and informant-report), objective memory performance, and medial temporal lobe (MTL) volume., Methods: MCI patients ( n =58) and their informants ( n =51) completed the Memory Assessment Clinics Self (MAC-S) and Family (MAC-F) rating scales as a measure of subjective memory. RBANS Immediate and Delayed Memory indices were used as objective measures of memory and a subset of MCI participants also underwent MRI, which was used to measure MTL volume., Results: Patients reported greater difficulty with semantically based information (e.g., word and name recall) relative to informant report. However, the severity of these self-reports was unrelated to objective memory performance and only a single MAC-S scale was related to amygdalar volume. Conversely, several MAC-F indices were related to the RBANS Delayed Memory index as well as to amygdalar and hippocampal volumes. Measures of executive functioning were associated with MAC-S Frequency scales but not any MAC-F scale., Discussion: The results of the current study suggest that, in those who are cognitively symptomatic, the frequency of self-reported subjective memory difficulty may reflect executive dysfunction but holds little value for verifying memory impairment. Conversely, informant report provides meaningful information about actual memory deficits in those with MCI.