Criteria For Mild Cognitive Impairment Research Articles

Updates in the Management of Mild Cognitive Impairment and Alzheimer Disease.

At the end of the activity, participants will be able to:Implement evidence-based methods for cognitive impairment screening in primary care. Identify correct diagnostic criteria for mild cognitive impairment (MCI) and Alzheimer disease (AD) based on current guideline recommendations. Design appropriate and effective treatment plans for patients with MCI and AD and refer to a specialist when necessary. Describe advances in testing and treatment for AD that may impact dementia care.

Prevalence and affective correlates of subjective cognitive decline in patients with de novo Parkinson's disease.

ObjectivesThe novel concept of subjective cognitive decline (SCD) in Parkinson's disease (PD) refers to subjective cognitive impairment without concurrent objective cognitive deficits. This study aimed to determine the prevalence and affective correlates of SCD in de novo PD patients.Materials and MethodsA total of 139 de novo PD patients underwent comprehensive neuropsychological evaluation. PD patients with SCD (PD‐SCD) did not meet the diagnostic criteria for mild cognitive impairment in PD (PD‐MCI) based on the Movement Disorder Society Level II Criteria and were defined by a Domain‐5 Score ≥1 on the Non‐Motor Symptoms Questionnaire. Affective symptoms were measured using the Hamilton Depression Scale (HAMD) and Hamilton Anxiety Scale (HAMA).ResultsIn de novo PD cohort, the prevalence of SCD was 28.1%. PD‐SCD patients performed significantly better than PD‐MCI patients on tests of five cognitive domains. The more commonly affected domains in PD‐SCD patients were memory (28.2%) and attention/working memory (25.6%). Multivariable linear regression analysis revealed that PD‐SCD was significantly associated with both HAMD (β = 4.518, 95% CI = 0.754–8.281, p = .019) and HAMA scores (β = 4.259, 95% CI = 1.054–7.464, p = .010). Furthermore, binary logistic regression analysis revealed that higher HAMD (OR = 1.128, 95% CI = 1.019–1.249, p = .020) and HAMA scores (OR = 1.176, 95% CI = 1.030–1.343, p = .017) increased the risk of PD‐SCD.ConclusionsOur findings suggest that SCD is highly prevalent in de novo PD patients. The presence of PD‐SCD is suggestive of an underlying affective disorder.

The Need for a Specialized Neurocognitive Screen and Consistent Cognitive Impairment Criteria in Spinal Cord Injury: Analysis of the Suitability of the Neuropsychiatry Unit Cognitive Assessment Tool.

The assessment of mild cognitive impairment (MCI) following spinal cord injury (SCI) is vital. However, there are no neurocognitive screens which have been developed specifically to meet the unique requirements for SCI, nor are there consistent MCI criteria applied to determine the rates of MCI. The aim of this study was to determine the suitability of a neurocognitive screen for assessing MCI in adults with SCI. A total of 127 participants were recruited. Socio-demographic and injury related variables were assessed. All participants completed the screen. Descriptive statistics are provided for total/domain screen scores and all items, and the screen’s ability to distinguish MCI was examined. Congeneric confirmatory factor analyses (CFA) were employed to investigate structural validity. The screen total score was sensitive to differences in neurocognitive capacity, as well as for time since the injury occurred (p < 0.01). The MCI rate ranged between 17–36%. CFA revealed attention and visuoconstruction domains had an adequate model fit and executive function had poor fit, while CFA models for memory and language did not fit the data (did not converge), hence could not be determined. While the screen differentiated between those with MCI and those without, and MCI as a function of time since injury, limitations of its suitability for assessing MCI after SCI exist, demonstrating the need for a specialized neurocognitive screen for adults with SCI.

Cognitive profile in idiopathic autonomic failure: relation with white matter hyperintensities and neurofilament levels.

ObjectiveTo disclose the nature of cognitive deficits in a cohort of patients with idiopathic autonomic failure (IAF) by exploring the relation among cognitive functions, cardiovascular autonomic failure (AF) and clinical progression to another α‐synucleinopathy (phenoconversion).MethodsWe retrospectively identified all patients with a clinical diagnosis of IAF who underwent a comprehensive neuropsychological evaluation, clinical examination and cardiovascular autonomic tests from the IAF‐BO cohort. Brain magnetic resonance imaging (MRI) studies and cerebrospinal fluid (CSF) analysis, including neurofilament light chain (NfL), Alzheimer disease core biomarkers, and α‐synuclein seeding activity were further evaluated when available.Correlations among cognitive functions, clinical features, cardiovascular AF, cerebral white matter hyperintensities (WMH) load, and CSF biomarkers were estimated using Spearman correlation coefficient.ResultsThirteen out of 30 (43%) patients with IAF displayed cognitive deficits (CI) mainly concerning executive functioning. Seven out of 30 (23%) met the criteria for mild cognitive impairment (MCI).The diagnosis of CI and MCI was not associated with phenoconversion or autonomic function parameters, including duration and severity of neurogenic orthostatic hypotension, presence and severity of supine hypertension, and nocturnal dipper profile.Twenty patients underwent a brain MRI and CSF analysis. MCI was related to WMH load (r = 0.549) and NfL levels (r = 0.656), while autonomic function parameters were not associated with either WMH or NfL levels.InterpretationCardiovascular AF and phenoconversion, underlying the spreading of neurodegeneration to the central nervous system, were not independent drivers of cognitive dysfunction in IAF. We identified WMH load and NfL levels as potential biomarkers of the neural network disruption associated with cognitive impairment in patients with IAF.

Deficits in Emotion Recognition and Theory of Mind in Parkinson's Disease Patients With and Without Cognitive Impairments.

BackgroundEmotion recognition and social deficits have been previously reported in Parkinson’s disease (PD). However, the extent of these impairments is still unclear and social cognition is excluded from the cognitive domains considered in the current criteria for PD mild cognitive impairment (MCI). This study aims to analyze emotion recognition, affective and cognitive theory of mind in early PD patients classified according to Level II MCI criteria, and to evaluate the prevalence of socio-cognitive deficits in this sample.MethodsWe enrolled 45 participants with PD, classified as cognitively unimpaired (CU; n = 32) or MCI (n = 13) based on a standard neuropsychological assessment. Social cognitive skills were evaluated through validated tests for emotion recognition (i.e., Ekman 60-faces test, Ek60 Test) and mental states attribution (Story-based Empathy Task, SET) and compared to a group of 45 healthy controls (HC). Between-group differences in social tasks were performed, as well as correlation analyses to assess the relationship between social, cognitive, and clinical variables. Finally, the number of patients with social cognitive impairments in both MCI and CU subgroups was computed based on Italian normative data.ResultsStatistical comparison revealed significant differences among groups in the Ek60 test, with MCI obtaining significantly lower scores than HC and CU, especially for negative emotions. Significant differences were detected also in the SET, with lower performance in emotion and intention attribution for both PD groups compared to HC. A significant correlation emerged between the Ek60 test and emotion attribution. Nine patients showed poor performance at social tasks, five of them being classified as PD-CU.DiscussionParkinson’s disease cognitive profile was characterized by emotion recognition and attribution deficits. These results, as well as the detection of CU patients with isolated socio-cognitive impairments, underline the importance of assessing social cognition in PD as a possible early marker of cognitive decline.

A Neuropsychological Approach to Mild Cognitive Impairment.

A neuropsychological approach to the detection and classification of mild cognitive impairment (MCI) using "gold standard" clinical ratings (CRs) was examined in a sample of independently functioning community dwelling seniors. The relationship between CRs and life satisfaction, concurrent validity of cognitive screening measures, and agreement between CRs and existing criteria for MCI were also determined. One hundred and forty-two participants, aged 75years and older, were administered a comprehensive battery of neuropsychological tests, along with self-report measures of psychological and psychosocial functioning, and functional independence. CRs were based on demographically corrected neuropsychological variables. The prevalence of MCI identified using CRs in this sample was 26.1%. Single and multiple domain subtypes of MCI were readily identified with subtypes reflecting Amnestic and Executive Function impairment predominating. Executive Function was a significant predictor of Life Satisfaction. The MoCA and MMSE both showed weak performance in detecting MCI based on CRs. There was substantial agreement between CRs and the classification criteria for MCI defined by Petersen/Winblad and Jak/Bondi. A global deficit score had near perfect performance as a proxy for CRs in detecting MCI in this sample. The results provide strong support for the utility of neuropsychological CRs as a "gold standard" operational definition in the detection and classification of MCI in older adults.

Profile of cognitive impairment in late-stage Parkinson's disease.

IntroductionThe profile of cognitive impairment associated with the late stages of Parkinson's disease (LSPD) is rarely reported. Its characterization is necessary to better understand the cognitive changes that occur as the disease progresses and to better contribute to its management.MethodsIn this cross‐sectional study, we characterized the cognitive profile of LSPD patients using the comprehensive assessment methodology proposed by the International Parkinson and Movement Disorders Society Task Force. The association of clinical and demographic variables with dementia diagnosis was also investigated using binary logistic regression analysis.ResultsEighty‐four LSPD patients were included (age 75.4 ± 6.9; disease duration 16.9 ± 7.5). Fifty‐four (64.3%) were classified as demented and presented a global impairment cognitive profile. In the nondemented group (N = 30), 25 (83.3%) LSPD patients met the diagnostic criteria for mild cognitive impairment, mostly with multiple domain impairment (96.0%) and a heterogeneous profile. Memory was the most frequent and severely impaired cognitive domain in both groups. Disease disability, orientation, complex order comprehension, verbal learning, and visuoconstructive abilities were significantly associated with dementia diagnosis (p < .05).ConclusionsCognitive impairment in multiple domains was common in LSPD patients. The most frequent and prominent deficits were in the memory domain, with a strong interference from attention impairment. Disease disability, orientation, complex order comprehension, verbal learning, and visuoconstructive abilities proved to be important determinants for dementia diagnosis.

Cognitive Test Scores and Progressive Cognitive Decline in the Aberdeen 1921 and 1936 Birth Cohorts.

The Aberdeen birth cohorts of 1921 and 1936 (ABC21 and ABC36) were subjected to IQ tests in 1932 or 1947 when they were aged about 11y. They were recruited between 1997–2001 among cognitively healthy community residents and comprehensively phenotyped in a long-term study of brain aging and health up to 2017. Here, we report associations between baseline cognitive test scores and long-term cognitive outcomes. On recruitment, significant sex differences within and between the ABC21 and ABC36 cohorts supported advantages in verbal ability and learning among the ABC36 women that were not significant in ABC21. Comorbid physical disorders were self-reported in both ABC21 and ABC36 but did not contribute to differences in terms of performance in cognitive tests. When used alone without other criteria, cognitive tests scores which fell below the −1.5 SD criterion for tests of progressive matrices, namely verbal learning, digit symbol and block design, did not support the concept that Mild Cognitive Impairment (MCI) is a stable class of acquired loss of function with significant links to the later emergence of a clinical dementia syndrome. This is consistent with many previous reports. Furthermore, because childhood IQ-type data were available, we showed that a lower cognitive performance at about 64 or 78 y than that predicted by IQ at 11 ± 0.5 y did not improve the prediction of progress to MCI or greater cognitive loss. We used binary logistic regression to explore how MCI might contribute to the prediction of later progress to a clinical dementia syndrome. In a fully adjusted model using ABC21 data, we found that non-amnestic MCI, along with factors such as female sex and depressive symptoms, contributed to the prediction of later dementia. A comparable model using ABC36 data did not do so. We propose that (1) MCI criteria restricted to cognitive test scores do not improve the temporal stability of MCI classifications; (2) pathways towards dementia may differ according to age at dementia onset and (3) the concept of MCI may require measures (not captured here) that underly self-reported subjective age-related cognitive decline.

Long-term cognitive impairments in kidney transplant recipients: impact on participation and quality of life.

Cognitive impairment is often present shortly after transplantation in kidney transplant recipients (KTR). To date, it is unknown whether these impairments persist in thelong term, to what extent they are associated with disease-related variables and whether they affect societal participation and quality of life (QoL) of KTR. This study was part of the TransplantLines Biobank & Cohort Study in the University Medical Center Groningen. A total of 131 KTR, with a mean age of 53.6 years (SD=13.5) transplanted≥1 year ago (M=11.2 years, range 1-41.7 years), were included and compared with 306 healthy controls (HC). KTR and HC were well matched; there were no significant differences regarding age, sex and education. All participants were assessed with neuropsychological tests measuring memory, mental speed, attention and executive functioning, and with questionnaires examining societal participation and QoL. Compared with HC, KTR performed significantly worse on memory, mental speed and measures of executive functioning (all P-values<0.05). Moreover, 16% of KTR met the criteria for mild cognitive impairment (MCI), compared with 2.6% of the HC. MCI in KTR was not significantly correlated with age- and disease-related variables. Poorer cognitive functioning was significantly related to lower levels of societal participation and to lower QoL (all P-values<0.01). This study shows long-term cognitive impairments in KTR, which are not related to disease-related variables. Neuropsychological assessment is important to timely signal these impairments, given their serious negative impact on societal participation and QoL.

Reducing misclassification of mild cognitive impairment based on base rate information from the Uniform data set

ABSTRACT The current study aimed to define and validate the criteria for characterizing possible and probable cognitive deficits based on the psychometric approach using the Uniform data set Czech version (UDS-CZ 2.0) to reduce the rate of misdiagnosis. We computed the prevalence of low scores on the 14 subtests of UDS-CZ 2.0 in a normative sample of healthy older adults and validated criteria for possible and probable cognitive impairment on the sample of amnestic Mild Cognitive Impairment (MCI) patients. The misclassification rate of the validation sample using psychometrically derived criteria remained low: for classification as possible impairment, we found 66–76% correct classification in the clinical sample and only 2–8% false positives in the healthy control validation sample, similar results were obtained for probable cognitive impairment. Our findings offer a psychometric approach and a computational tool to minimize the misdiagnosis of mild cognitive impairment compared to traditional criteria for MCI.

S327 phosphorylation of the presynaptic protein SEPTIN5 increases in the early stages of neurofibrillary pathology and alters the functionality of SEPTIN5

Alzheimer's disease (AD) is the most common form of dementia, which is neuropathologically characterized by extracellular senile plaques containing amyloid-β and intracellular neurofibrillary tangles composed of hyperphosphorylated tau protein. Previous studies have suggested a role for septin (SEPTIN) protein family members in AD-associated cellular processes. Here, we elucidated the potential role of presynaptic SEPTIN5 protein and its post-translational modifications in the molecular pathogenesis of AD. RNA and protein levels of SEPTIN5 showed a significant decrease in human temporal cortex in relation to the increasing degree of AD-related neurofibrillary pathology. Conversely, an increase in the phosphorylation of the functionally relevant SEPTIN5 phosphorylation site S327 was observed already in the early phases of AD-related neurofibrillary pathology, but not in the cerebrospinal fluid of individuals fulfilling the criteria for mild cognitive impairment due to AD. According to the mechanistic assessments, a link between SEPTIN5 S327 phosphorylation status and the effects of SEPTIN5 on amyloid precursor protein processing and markers of autophagy was discovered in mouse primary cortical neurons transduced with lentiviral constructs encoding wild type SEPTIN5 or SEPTIN5 phosphomutants (S327A and S327D). C57BL/6 J mice intrahippocampally injected with lentiviral wild type SEPTIN5 or phosphomutant constructs did not show changes in cognitive performance after five to six weeks from the start of injections. However, SEPTIN5 S327 phosphorylation status was linked to changes in short-term synaptic plasticity ex vivo at the CA3-CA1 synapse. Collectively, these data suggest that SEPTIN5 and its S327 phosphorylation status play a pivotal role in several cellular processes relevant for AD.

Swallowing Dynamics and Breathing-Swallowing Coordination Are Altered in Patients with Mild Cognitive Impairment

Introduction: Postinspiratory activity, which is essential for laryngeal closure during swallowing to prevent aspiration of food into the airways, is reduced in a mouse model of tauopathy. Therefore, we hypothesized that patients at the stage of mild cognitive impairment (MCI) exhibit alterations in swallowing dynamics and coordination between swallowing and breathing. Methods: We examined breathing-swallowing coordination in patients with MCI. Patients who scored ≥24 on the Mini-Mental State Examination and <26 on the Japanese version of the Montreal Cognitive Assessment were recruited at Sumoto Itsuki Hospital. Parameters associated with breathing-swallowing coordination were assessed using a combination of two sensors: a respiratory flow sensor and a piezoelectric sensor attached to the skin surface of the anterior neck. Results: Nineteen patients met the criteria for MCI; 16 of these patients (79.5 ± 9.1 years old) scored <3 on the 10-item Eating Assessment Tool and were enrolled in the study. Their data were compared with those of an age-matched elderly cohort (79.9 ± 2.9 years old). The frequencies of swallowing during inspiration and swallowing immediately followed by inspiration in patients with MCI were 6.9% and 9.6%, respectively; these frequencies were not significantly different from those of the age-matched elderly cohort. However, the timing of swallowing in the respiratory cycle was significantly delayed in the MCI patients, and both time from the onset to the peak of laryngeal elevation and the duration between the onset of rapid laryngeal elevation and the time when the larynx returned to the resting position were significantly lengthened in this group. Conclusion: At the stage of MCI, breathing-swallowing coordination has already started to decline.

Variability in Cognitive Performance on Mobile Devices Is Sensitive to Mild Cognitive Impairment: Results From the Einstein Aging Study.

Background and Objective: Within-person variability in cognitive performance has emerged as a promising indicator of cognitive health with potential to distinguish normative and pathological cognitive aging. We use a smartphone-based digital health approach with ecological momentary assessments (EMA) to examine differences in variability in performance among older adults with mild cognitive impairment (MCI) and those who were cognitively unimpaired (CU).Method: A sample of 311 systematically recruited, community-dwelling older adults from the Einstein Aging Study (Mean age = 77.46 years, SD = 4.86, Range = 70–90; 67% Female; 45% Non-Hispanic White, 40% Non-Hispanic Black) completed neuropsychological testing, neurological assessments, and self-reported questionnaires. One hundred individuals met Jak/Bondi criteria for MCI. All participants performed mobile cognitive tests of processing speed, visual short-term memory binding, and spatial working memory on a smartphone device up to six times daily for 16 days, yielding up to 96 assessments per person. We employed heterogeneous variance multilevel models using log-linear prediction of residual variance to simultaneously assess cognitive status differences in mean performance, within-day variability, and day-to-day variability. We further tested whether these differences were robust to the influence of environmental contexts under which assessments were performed.Results: Individuals with MCI exhibited greater within-day variability than those who were CU on ambulatory assessments that measure processing speed (p < 0.001) and visual short-term memory binding (p < 0.001) performance but not spatial working memory. Cognitive status differences in day-to-day variability were present only for the measure of processing speed. Associations between cognitive status and within-day variability in performance were robust to adjustment for sociodemographic and contextual variables.Conclusion: Our smartphone-based digital health approach facilitates the ambulatory assessment of cognitive performance in older adults and the capacity to differentiate individuals with MCI from those who were CU. Results suggest variability in mobile cognitive performance is sensitive to MCI and exhibits dissociative patterns by timescale and cognitive domain. Variability in processing speed and visual short-term memory binding performance may provide specific detection of MCI. The 16-day smartphone-based EMA measurement burst offers novel opportunity to leverage digital technology to measure performance variability across frequent assessments for studying cognitive health and identifying early clinical manifestations of cognitive impairment.

Comparison of actuarial and conventional MCI criteria in a community‐based prospective cohort study: The Adult Changes in Thought (ACT) study

AbstractBackgroundOperationalizations of mild cognitive impairment (MCI) are inconsistent. Actuarial criteria have been proposed to improve accuracy. We investigated dementia and Alzheimer’s disease (AD) conversion for conventional versus actuarial MCI criteria in a community‐based prospective cohort study.Method1413 non‐demented participants were administered measures from memory, language, and attention/executive function domains. We used published norms to generate demographically‐adjusted z‐scores. Conventional MCI criteria were met for scores &gt;1.5sd below the mean on any measure. Actuarial MCI criteria were met for 2 scores &gt;1.0sd below the mean in one domain or a score &gt;1.0sd below the mean in all three domains. Participants were followed biennially to capture dementia incidence. A consensus conference used DSM‐IV dementia criteria and NINDS‐ADRDA AD criteria for diagnosis. We focused on 6‐year outcomes following MCI categorization.ResultAt baseline, n=875 (62%) met neither conventional nor actuarial MCI criteria, n=16 (1%) met only actuarial MCI criteria, n=383 (27%) met only conventional MCI criteria, and n=139 (10%) met both. Demographic characteristics are in Table 1. Education differed across criteria (p&lt;0.0001); more people with lower education met only conventional MCI criteria. During follow up (7090 person‐years, mean=5 years), there were 175 incident dementia cases, of whom 110 (63%) met conventional and 53 (30%) met actuarial MCI criteria at their baseline neuropsychological evaluation. In a Cox model adjusting for age, sex, education, and race/ethnicity, the conventional MCI dementia hazard ratio (HR) was 2.93 (95% CI 2.15, 4.01, p&lt;0.001), and the actuarial MCI HR was 3.62 (95% CI 2.60, 5.03; p&lt;0.001). There were 154 incident AD cases; 101 (66%) met conventional and 49 (32%) met actuarial criteria. The adjusted conventional MCI AD HR was 3.25 (95% CI 2.32, 4.56, p&lt;0.001), and the actuarial MCI AD HR was 3.81 (95% CI 2.69, 5.38, p&lt;0.001).ConclusionBoth conventional and actuarial MCI criteria identified individuals at higher risk of developing dementia and AD over 6 years of follow‐up. Conventional criteria flag a higher proportion of those who ultimately developed dementia and AD compared to actuarial criteria. However, hazard ratios for progression to dementia and AD were slightly higher for the actuarial criteria.

How often is EEG used as part of routine dementia evaluation in community practice?

AbstractBackgroundRecommendations for evaluation of patients with dementia have changed little in the last thirty years. The guideline for diagnosis of dementia published by the American Academy of Neurology (AAN) in 1984 recommended against routine use of EEG for evaluation of dementia, and in the updated guideline from 2001 EEG is not specifically mentioned. Some authors continue to argue for use of EEG in dementia research, though mostly this focuses on specialized EEG techniques like quantitative EEG. There are few reports, however, on the frequency of EEG use in community neurological evaluations for dementia.MethodAll new patient referrals to the Novant Health Memory Clinic in Charlotte, NC, for 2020 were reviewed. Information was tabulated for those patients who had been previously evaluated by a neurologist in the community, specifically to determine how often EEG was included as part of the routine evaluation. Results of the EEG as taken from the clinician’s report were tabulated, though there was no opportunity to examined the EEG tracing itself. The author made a judgement as to whether the results of the EEG affected the clinical diagnosis or provided useful information for management of the patient in each case, and these data were tabulated.ResultDuring the year of observation, there were a total of 845 new patient evaluations in the Memory Clinic. Of those, 274 patients met clinical criteria for “Probable” Alzheimer Disease, 237 met criteria for Mild Cognitive Impairment, and 207 for Subjective Cognitive Decline. Out of these patients, 89 had been previously evaluated by a community neurologist. In 63 of the evaluations, EEG was obtained as part of the routine evaluation. Of these, 16 were read as “normal,” and 47 were read as “abnormal” due to slowing of background rhythm. In 2 of the 47, the reader also reported finding “sharp waves” in temporal leads, and these 2 patients were treated by the reading neurologist with anticonvulsants, later discontinued in both cases. In no case did the EEG provide useful information for either diagnosis of management of dementia.ConclusionThese data support the AAN guideline’s recommendation against routine use of EEG for dementia evaluation.

Cognitive correlations with amyloid, tau and neurodegeneration PET across the Alzheimer’s disease age spectrum

AbstractBackgroundIn Alzheimer’s disease (AD), cognitive symptoms have varying associations with tau, amyloid and neurodegeneration. Patients with early‐onset AD (EOAD, age&lt;65) have more non‐amnestic symptoms, greater AD pathological burden, and less co‐pathologies than late‐onset AD (LOAD, age≥65). It is unknown whether the association between cognitive symptoms and Alzheimer’s disease biomarkers differs with age, and this has implications for clinical trials. The goal of this study was (1) to evaluate the association between domain‐specific cognitive performance and PET‐based pathology in AD, and (2) to compare whether theses associations differ in EOAD versus LOAD.MethodAmyloid‐positive patients meeting criteria for mild cognitive impairment or AD dementia (Total n=71; EOAD n=33, mean age 58±4, MMSE 20±7, 61% female; LOAD n=38, mean age 74±6, MMSE 24±5, 45% female) underwent neuropsychological testing, 18F‐flortaucipir (FTP‐PET), 11C‐PIB‐PET (PIB‐PET), and a subset underwent 18F‐fluorodeoxyglucose‐PET (FDG‐PET, n=57). Composite scores were calculated for episodic memory, semantic memory, language, executive function and visuospatial domains. Voxelwise regressions (thresholded at uncorrected p&lt;0.001 voxel‐level, FWE p&lt;0.05 cluster‐level) evaluated PET/cognition correlations, and EOAD versus LOAD differences were tested with a PET*group interaction. Mediation analyses assessed direct and FDG‐PET‐mediated associations between FTP‐PET and cognitive performance in regions‐of‐interest based on the voxelwise regressions.ResultsFTP‐PET and FDG‐PET (lesser extent), but not PIB‐PET, showed significant domain‐specific voxelwise associations with cognitive performance that aligned with known brain‐behavior relationships (episodic memory/medial temporal lobe, semantic memory/anterior temporal, language/perisylvian, executive/frontal, visuospatial/occipital) (Figures 1‐3). There were no significant interactions between age and PET correlations across all modalities. Mediation analysis revealed that FDG‐PET mediated the relationship between FTP‐PET and cognition in all domains except episodic memory (Table 1). FTP‐PET also had a direct effect on executive function (p&lt;0.001) and visuospatial (p=0.02) performance.ConclusionIn AD, cognitive performance correlated with tau and neurodegeneration, but not amyloid, in similar patterns across the age spectrum. The relationship between tau and cognition was in part mediated by glucose metabolism. These findings provide support for inclusion of EOAD patients in clinical trials, for tau PET as a biomarker that captures molecular specificity and aligns with clinical performance, and for the shared potential of disease‐modifying therapies across the AD age spectrum.

Cognitive performance predictors of incident motoric cognitive risk syndrome

AbstractBackgroundMotoric cognitive risk syndrome (MCR) is a gait based pre‐dementia syndrome that builds on operational definitions of mild cognitive impairment (MCI), and is associated with increased risk for Alzheimer’s Disease and other types of dementia. Declines in cognitive function associated with risk of developing MCR have not been established. We aimed to examine the association between cognitive performance on tests of memory and executive function (EF) and related processes and risk of incident MCR.MethodOf the 541 non‐demented participants (aged 65+) in a community‐based cohort, at baseline 22 met criteria for MCR, 58 for MCI, and 17 met criteria for both MCR and MCI, and were excluded from the analyses. Cognitive performance was measured using seven tests: the free recall score from the Free and Cued Selective Reminding Test, Figure Recall from the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), Story Recall from the RBANS, Category Fluency, Controlled Oral Word Association Test, Digit Symbol Substitution test and Trail Making Test part B. A confirmatory factor analysis indicated that these cognitive tests fell into two categories of cognitive function: memory and EF and related processes. Cox proportional hazard models adjusted for age, sex and education was used to examine the association between cognitive test performance and incident MCR in 444 participants. For the purpose of comparison, we also examined the association between cognitive performance and MCI.ResultOver a mean follow‐up of 3.0 years, 37 participants developed incident MCR and 69 incident MCI. Performance on tests of EF and related processes was associated with risk for MCR (adjusted hazard ratios (aHR) ranging from 0.96 to 0.99). One memory test (free recall) was associated with risk of MCR (aHR: 0.94, 95% Confidence Interval: 0.89‐0.99). Performance on all tests of memory (aHR ranging from 0.81 to 0.92) and EF and related processes (HR ranging from 0.94 to 0.99) was associated with increased risk of MCI.ConclusionCognitive performance on tests of EF and related processes are associated with increased risk of MCR. This may be indicative of a distinct underlying pathology in patients who are at risk of MCR.

Evidence for the role of semantic cueing and executive functioning tools in early and differential diagnosis of neurocognitive disorder (NCD): A neuropsychological approach

AbstractBackgroundRecent advances in the diagnosis of Mild Cognitive Impairment (MCI) and Neurocognitive Disorders (NCDs) build on neuropsychological models (Dodich et al., 2018; Possin et al., 2018). Despite the lack of harmonized protocols (Costa et al., 2017), tools such as the Free and Cued Selective Reminding Test (FCSRT) yield specific scores (e.g., ISC for cue sensitivity) for the early detection of hippocampal syndromes involved in Alzheimer’s Disease (AD), and for the prediction of MCI‐to‐AD conversion (Brugnolo et al., 2021). Accordingly, the study aims to investigate the correlation between neuropsychological profiles and cognitive patterns through an extensive assessment procedure accounting for the heterogeneity of MCI and NCDs.MethodsN=150 outpatients (mean age=72.29±5.42 SD) were administered a battery meeting both MCI (Petersen et al., 2014) and NCD criteria (APA, 2013) including: two screening tools; ten domain‐specific cognitive tests; psychodiagnostic‐functional assessment. Analyses through paired‐sample tests and multivariate models focused on: (1) episodic memory and executive deficits; (2) predictive indices for MCI/NCD diagnosis.Results70.7% of the clinical sample obtained scores consistent with MCI or mildNCD profiles, and 75% showed episodic memory impairment on cut‐off basis (FCSRT‐ISC&lt;0.9). Wilcoxon signed‐rank test revealed poorer performance in FCSRT‐ISC compared to Babcock Story‐IR (p‐value&lt;0,001&lt;α=0,05), notably in MCI/mildNCDs but not in majorNCDs. The full sample and MCI/mildNCD subset also obtained lower scores in Digit Span Backward (DS‐B) than in the Clock Drawing Test (CDT), whereas majorNCD performed worse in CDT. Logistic regression showed three predictive indices for majorNCD: the lower the scores on FCSRT‐IFR, DS‐B and CDT, the greater the chances of fitting majorNCD profile.ConclusionDriven by the need for early and differential diagnosis of NCDs, our findings showed episodic memory impairment within the total sample and the MCI/mildNCD subsets, indicating: (1) a high prevalence of AD‐type MCI/mildNCDs; (2) the possible key role of FCSRT‐ISC in detecting early or mild conditions of impairment; (3) the good predictive values (86%) of some memory (i.e. FCSRT‐IFR) and executive tasks (i.e. DS‐B and CDT) contributing to a major NCD diagnosis, potentially enhancing NCD nosography and differential diagnosis.

Use of amyloid PET scans in the clinical management of patients with cognitive decline in a naturalistic setting at a tertiary memory disorders clinic

AbstractBackgroundAmyloid PET(aPET) is used to aid differential diagnosis, increase diagnostic confidence and assist with management of patients with cognitive decline. In the United States, aPETs are not often used because they are costly and not covered by insurance. VA Boston Healthcare System provides a unique opportunity where aPETs are available for clinical purposes and are ordered to assist in the differential diagnosis of patients with cognitive decline when clinically relevant. This study aims to determine which factors are associated with the use of aPET for diagnostic confirmation of AD in a naturalistic setting at a tertiary memory disorders clinic and to determine which factors predict an abnormal result.MethodWe conducted a retrospective review of all patients that were evaluated for cognitive decline at the Memory Disorders Clinic at Boston VA Medical Center from 9/2016 to 1/2020. Clinical information was extracted, including demographics, neuropsychological testing, and imaging studies. We compared patients' characteristics for whom an aPET was ordered and those for who a diagnosis was made without an aPET. We reviewed the characteristics of patients with positive vs. negative aPETResult565 patients were evaluated. 202 patients (35.75%) had an aPET as part of their workup; of these, 72 patients (36.5%) had an abnormal result. Factors associated with clinicians ordering the aPET were: younger age, longer clinical course, absence of amyloid angiopathy on MRI, and a diagnosis of mild cognitive impairment (MCI) and mild dementia. When performing multivariate analysis of the clinical characteristics, imaging, and neuropsychological tests of patients, only a positive family history of dementia (p=0.004) and presence of false‐positives on recognition in the CERAD list learning task (p=0.004) were associated with an abnormal result.ConclusionIn this cohort, aPETs were ordered in younger patients who fulfilled the criteria for MCI and mild dementia, and had a longer clinical course. Only a family history of dementia and false‐positives on recognition during a list learning task were significantly associated with an abnormal result. The results of this study may be informative both regarding how aPET may be used if covered by insurance and regarding clues to determining underlying Alzheimer’s pathology without biomarkers.

Predictors of Incident Mild Cognitive Impairment and Its Course in a Diverse Community-Based Population.

Background and ObjectivesTo investigate sociodemographic and medical predictors of incident mild cognitive impairment (MCI) and subsequent course of MCI at follow-up, including sustained MCI diagnosis, classification as cognitively normal, and progression to dementia.MethodsWithin a community-based cohort, diagnoses of MCI were made with a published algorithm. Diagnosis of dementia was based on clinical consensus. Cox regressions estimated hazard ratios of incident MCI associated with several predictors. Modified Poisson regressions estimated relative risks associated with predictors of diagnostic status at follow-up after incidence.ResultsAmong 2,903 cognitively normal participants at baseline, 752 developed MCI over an average of 6.3 (SD 4.5) years (incidence rate 56 per 1,000 person-years). Presence of APOE ε4 and higher medical burden increased risk of incident MCI, while more years of education, more leisure activities, and higher income decreased this risk. Of the incident MCI cases, after an average of 2.4 years of follow-up, 12.9% progressed to dementia, 9.6% declined in functioning and did not meet the algorithmic criteria for MCI but did not meet the clinical criteria for dementia, 29.6% continued to meet MCI criteria, and 47.9% no longer met MCI criteria. Multidomain MCI, presence of APOE ε4, depressive symptoms, and antidepressant use increased the risk of progression to dementia.DiscussionThis community-based study showed that almost half of the individuals with incident MCI diagnoses were classified as cognitively normal at follow-up. Predictors of incident MCI demonstrably differed from those of subsequent MCI course; these findings can refine expectations for cognitive and functional course of those presenting with MCI.