Predictor Of Cognitive Decline Research Articles

Exploring electrophysiological markers of auditory predictive processes and pathological ageing in adults with Down's syndrome.

Down's syndrome is associated with pathological ageing and a propensity for early-onset Alzheimer's disease. The early symptoms of dementia in people with Down's syndrome may reflect frontal lobe vulnerability to amyloid deposition. Auditory predictive processes rely on the bilateral auditory cortices with the recruitment of frontal cortices and appear to be impaired in pathologies characterized by compromised frontal lobe. Hence, auditory predictive processes were investigated to assess Down's syndrome pathology and its relationship with pathological ageing. An auditory electroencephalography (EEG) global-local paradigm was presented to the participants, in which oddball stimuli could either violate local or higher level global rules. We characterised predictive processes in individuals with Down's syndrome and their relationship with pathological ageing, with a focus on the EEG event-related potential called Mismatch Negativity (MMN) and the P300. In Down's syndrome, we also evaluated the EEG components as predictor of cognitive decline 1 year later. We found that predictive processes of detection of auditory violations are overall preserved in Down's syndrome but also that the amplitude of the MMN to local deviancies decreases with age. However, the 1-year follow-up of Down's syndrome found that none of the ERPs measures predicted subsequent cognitive decline. The present study provides a novel characterization of electrophysiological markers of local and global predictive processes in Down's syndrome.

A Review of the Measurement of the Neurology of Gait in Cognitive Dysfunction or Dementia, Focusing on the Application of fNIRS during Dual-Task Gait Assessment

Poor motor function or physical performance is a predictor of cognitive decline. Additionally, slow gait speed is associated with poor cognitive performance, with gait disturbances being a risk factor for dementia. Parallel declines in muscular and cognitive performance (resulting in cognitive frailty) might be driven primarily by muscle deterioration, but bidirectional pathways involving muscle–brain crosstalk through the central and peripheral nervous systems are likely to exist. Following screening, early-stage parallel declines may be manageable and modifiable through simple interventions. Gait–brain relationships in dementia and the underlying mechanisms are not fully understood; therefore, the current authors critically reviewed the literature on the gait–brain relationship and the underlying mechanisms and the feasibility/accuracy of assessment tools in order to identify research gaps. The authors suggest that dual-task gait is involved in concurrent cognitive and motor activities, reflecting how the brain allocates resources when gait is challenged by an additional task and that poor performance on dual-task gait is a predictor of dementia onset. Thus, tools or protocols that allow the identification of subtle disease- or disorder-related changes in gait are highly desirable to improve diagnosis. Functional near-infrared spectroscopy (fNIRS) is a non-invasive, cost-effective, safe, simple, portable, and non-motion-sensitive neuroimaging technique, widely used in studies of clinical populations such as people suffering from Alzheimer’s disease, depression, and other chronic neurological disorders. If fNIRS can help researchers to better understand gait disturbance, then fNIRS could form the basis of a cost-effective means of identifying people at risk of cognitive dysfunction and dementia. The major research gap identified in this review relates to the role of the central/peripheral nervous system when performing dual tasks.

Ankle-Brachial Index and Cardio-Ankle Vascular Index as Predictors of Cognitive Decline Over Time After Carotid Endarterectomy.

Objective: Patients with carotid stenosis risk cognitive impairment even after carotid endarterectomy (CEA) because of the long-term presence of vascular risk factors. Early prediction of cognitive decline is useful because early appropriate training for impaired cognitive domains can improve their functions. Ankle-brachial index (ABI) and cardio-ankle vascular index (CAVI) are frequently used as general indicators of systemic atherosclerosis and are associated with cognitive function in the general population. This study aimed to evaluate the utility of those vascular biomarkers for predicting cognitive decline in patients after CEA.Methods: Patients who had undergone both CEA at our institute and cognitive evaluations between March 2016 and January 2022 were invited to participate in this study. Associations between ABI or CAVI three years before baseline and cognitive function at baseline were assessed retrospectively in 94 patients, and associations between ABI or CAVI at baseline and three-year changes in cognitive functions were assessed prospectively in 24 patients. Cognitive functions were assessed using the Frontal Assessment Battery (FAB) and Neurobehavioral Cognitive Status Examination (Cognistat).Results: Low ABI three years before baseline was associated with poor performances on Cognistat and FAB at baseline. ABI, as a continuous measure, three years before baseline, showed positive linear associations with total Cognistat score and subscores for naming, construction, and judgment at baseline. The Wilcoxon signed-rank test showed that the total Cognistat score, total FAB score, and subscores for attention and inhibitory control declined after three years. CAVI at baseline was negatively associated with three-year changes in total Cognistat score and subscores for naming, construction, and memory.Conclusion: Cognitive function can decline over time in patients with carotid stenosis even after CEA. ABI and CAVI might be useful to predict cognitive function and its decline among patients who have undergone CEA.

Classification of early-MCI patients from healthy controls using evolutionary optimization of graph measures of resting-state fMRI, for the Alzheimer's disease neuroimaging initiative.

Identifying individuals with early mild cognitive impairment (EMCI) can be an effective strategy for early diagnosis and delay the progression of Alzheimer’s disease (AD). Many approaches have been devised to discriminate those with EMCI from healthy control (HC) individuals. Selection of the most effective parameters has been one of the challenging aspects of these approaches. In this study we suggest an optimization method based on five evolutionary algorithms that can be used in optimization of neuroimaging data with a large number of parameters. Resting-state functional magnetic resonance imaging (rs-fMRI) measures, which measure functional connectivity, have been shown to be useful in prediction of cognitive decline. Analysis of functional connectivity data using graph measures is a common practice that results in a great number of parameters. Using graph measures we calculated 1155 parameters from the functional connectivity data of HC (n = 72) and EMCI (n = 68) extracted from the publicly available database of the Alzheimer’s disease neuroimaging initiative database (ADNI). These parameters were fed into the evolutionary algorithms to select a subset of parameters for classification of the data into two categories of EMCI and HC using a two-layer artificial neural network. All algorithms achieved classification accuracy of 94.55%, which is extremely high considering single-modality input and low number of data participants. These results highlight potential application of rs-fMRI and efficiency of such optimization methods in classification of images into HC and EMCI. This is of particular importance considering that MRI images of EMCI individuals cannot be easily identified by experts.

Plasma MIA, CRP, and Albumin Predict Cognitive Decline in Parkinson's Disease.

Using a multi-cohort, discovery-replication-validation design, we sought new plasma biomarkers that predict which individuals with Parkinson's disease (PD) will experience cognitive decline. In 108 discovery cohort PD individuals and 83 replication cohort PD individuals, we measured 940 plasma proteins on an aptamer-based platform. Using proteins associated with subsequent cognitive decline in both cohorts, we trained a logistic regression model to predict which patients with PD showed fast (>=1 point drop/year on Montreal Cognitive Assessment [MoCA]) versus slow (< 1 point drop/year on MoCA) cognitive decline in the discovery cohort, testing it in the replication cohort. We developed alternate assays for the top 3 proteins and confirmed their ability to predict cognitive decline - defined by change in MoCA or development of incident mild cognitive impairment (MCI) or dementia - in a validation cohort of 118 individuals with PD. We investigated the top plasma biomarker for causal influence by Mendelian randomization (MR). A model with only 3 proteins (melanoma inhibitory activity protein [MIA], C-reactive protein [CRP], and albumin) separated fast versus slow cognitive decline subgroups with an area under the curve (AUC) of 0.80 in the validation cohort. The individuals with PD in the validation cohort in the top quartile of risk for cognitive decline based on this model were 4.4 times more likely to develop incident MCI or dementia than those in the lowest quartile. Genotypes at MIA single nucleotide polymorphism (SNP) rs2233154 associated with MIA levels and cognitive decline, providing evidence for MIA's causal influence. An easily obtained plasma-based predictor identifies individuals with PD at risk for cognitive decline. MIA may participate causally in development of cognitive decline. ANN NEUROL 2022;92:255-269.

Relationship between apathy and cognitive dysfunctions in multiple sclerosis: A 4-year prospective longitudinal study

BackgroundCognitive dysfunctions are highly prevalent in multiple sclerosis (MS) and negatively impact occupational and social functioning. ObjectiveIn the present longitudinal study, we aimed at modeling cognitive changes and at assessing whether apathy could be a predictor of cognitive decline in MS. MethodsWe assessed 67 people with MS at two-time points (baseline, T0; 4-year follow-up, T1), by means of several clinical, behavioural, and cognitive measures. We used a delta approach to measure cognitive decline during the follow-up period. We applied a mixed factorial design and a linear regression model to explore factors associated with cognitive changes over time. ResultsA higher level of apathy at baseline predicted the progressive cognitive decline at follow-up, whereas a higher level of depression did not. Among demographic and clinical characteristics, only low education level was significantly associated with cognitive decline over time. Interestingly, participants with persistent apathy (diagnosis of apathy at T0 and T1, A+A+) and those who developed apathy (A-A+) showed poorer inhibitory control and a larger decline in executive functioning during the 4-year follow-up than participants who had never received the diagnosis of apathy (A-A-). ConclusionApathy represents an early marker of cognitive decline in MS. These findings have important clinical and prognostic implications.

0636 Objective sleep as a predictor of cognitive decline among non-demented elderly: preliminary results from the Cretan Aging Cohort

Abstract Introduction Sleep disturbances have been linked with cognitive decline and previous cross-sectional have shown that long sleep duration is a marker of disease severity in patients Mild Cognitive Impairment (MCI) and Dementia.Our aim was to examine the longitudinal associations between sleep quantity and quality indices and cognitive progression in non-demented community-dwelling elderly. Methods A sub-sample of 62 participants (72.6% females) were recruited from a large population-based cohort in the island of Crete, Greece of 3,140 older adults (&amp;gt;60yrs). Participants were followed-up 8 years later (phase III). All participants underwent neuropsychiatric/neuropsychological evaluation (phases II &amp; III) and a 3-day 24h actigraphy (phase II).Participants were diagnosed as CNI(N=38) and MCI(N=24) during phase II, and CNI (N=22), MCI (N=27) and Dementia (N=13) during phase III. On follow-up, 28 participants progressed to a cognitively declined diagnosis compared to phase II (deteriorated group), while 34 did not (non-deteriorated group). Objective sleep variables at phase II were compared between the deteriotated/non-deteriorated groups using ANCOVA controlling for confounders. Also, differences in neuropsychological testing scores (phase II- phase III) were calculated and associations of differences with sleep variables were examined using partial correlation models controlling for confounders. Results The deteriorated group compared to non-deteriorated had significantly longer night total sleep time (TST) (442±72.6min vs. 407±53.6min, p=0.033), 24h-TST (484±8.9min vs. 434±66.4min, p=0.008), night time in bed (TMB) (537±78.7min vs. 497±62.7min, p=0.03), and 24h-TMB (603±85min vs. 539±85min, p=0.005). Episodic memory worsening was moderately correlated with night TST (r=.316), night and 24h-TMB (r=.526, and r= .442 respectively), wake time after sleep onset (r=.351), and average duration of night awakenings (r=.405). Immediate episodic memory recall decline was positively correlated with night TMB (r=.338). Conclusion Preliminary results from the Cretan aging cohort indicate that almost half of the participants deteriorated cognitively in 8 years and this decline was predicted by objective sleep duration at baseline. Long sleep at baseline may predict deterioration of clinical cognitive status in non-demented elderly at follow-up. It appears that prolonged objective sleep duration and time in bed are novel and clinically useful prognostic factors of cognitive deterioration in elderly with or without cognitive deficits. Support (If Any) National Strategic Reference Framework (NSRF) - Research Funding Program: THALES entitled “UOC-Multidisciplinary network for the study of Alzheimer’s Disease” Grant Cod: MIS 377299HELLENIC FOUNDATION FOR REASEARCH AND INNOVATION (HFRI)- Research Funding Program: ELIDEK entitled “Sleep Apnea (OSA) and poor sleep as Risk Factors for decreased cognitive performance in patients with Mild Cognitive Impairment: the Cretan Aging Cohort (CAC)”, Grant Cod: HFR1-FM17-4397

Association between physical and cognitive function in post menopause: a cross-sectional study

Functional tests have been performed to predict cognitive decline in postmenopausal women and may be an important tool to identify early reductions in cognitive performance in this population. However, it is still unclear which functional test is more sensitive for detecting cognitive decline in the investigated sample. The aim of this study was to verify the association between functional performance and cognitive function in postmenopausal women and to analyze whether the gait speed of 400 meters (400wt) and Timed Up and Go (TUG) tests are predictors of cognitive function in this sample. One hundred and twenty eight postmenopausal women (60.8 ± 7.9 years) participated in this cross-sectional study. Body composition was assessed using Dual Energy X-ray Absorptiometry (DXA), functional performance by the TUG and 400wt tests, cognitive performance by the Montreal Cognitive Assessment (MoCA) test and muscle strength by maximum voluntary isometric contraction (MVIC) in lower limbs. An association between functional performance and cognitive function was observed in middle-aged postmenopausal women. The TUG test was associated with the MoCA test (B = -0.79; SE = 0.29; p = 0.008). However, no association was observed between 400wt with the MoCA test (B = 3.03; SE = 1.92; p = 0.117). These results show that the TUG test is a good predictor of cognitive decline in postmenopausal middle-aged women.

Handgrip Strength and Cognitive Function among Elderly Koreans: Insights from the Korean Longitudinal Study of Ageing.

This study aims to assess handgrip strength as a predictor of cognitive decline within men and women in Korea. A random-intercept logistic regression is fit to estimate the status changes in cognitive function throughout all rounds of the KLoSA, a nationally-representative survey of adults aged 45 years and older. Males in the highest quartile were 71.9% less likely to experience cognitive impairment than those in the lowest quartile. The odds of cognitive impairment for men in the third and second quartiles reduced by 62.6% and 60.4% respectively. Similarly, the odds of cognitive impairment for women declined as 72.7%, 63.0%, and 41.8% for fourth, third, and second quartile, respectively, compared with the lowest quartile. These results imply that assessing and monitoring handgrip strength may enable us to identify subgroups of the elderly with higher likelihood of cognitive impairment in Korea.

Depressive symptoms predict memory decline in Essential Tremor

IntroductionEssential tremor (ET), a common movement disorder, is characterized by motor, cognitive and psychiatric symptoms. Depressed mood, a symptom of ET, has historically been viewed as a psychological response to disability. However, depressive symptoms are emerging as a predictor of cognitive decline across several clinical populations. We examined if depressive symptoms predict decline in global cognition, memory, and executive functioning among older adults with ET. Methods125 cognitively normal participants with ET completed three in-person assessments of cognition, mood, and motor symptoms at baseline, 18 months, and 36 months; baseline data were collected from July 2014–July 2016. Depressive symptoms were measured with the Geriatric Depression Scale. Cognitive functioning was measured via a 3-4 hour neuropsychological evaluation. Generalized linear regression models examined depressive symptoms as a predictor of decline in global cognition, executive functioning (EF), and memory. ResultsParticipants were grouped according to a median split (GDS <5 versus ≥ 5) due to the bimodal distribution of the data. In unadjusted models, depressive symptoms did not predict change in global cognition (b = −0.002, p = .502) or EF (b = 0.000, p = .931), however individuals with GDS ≥ 5 demonstrated faster memory decline in unadjusted (b = −0.008, p = .039) and adjusted models (b = −0.009, p = .019). ConclusionThe presence of 5 or more depressive symptoms predicted mildly faster memory decline in cognitively normal older adults with ET over 36 months. We discuss potential mechanisms and clinical implications.

Higher-Level Executive Functions in Healthy Elderly and Mild Cognitive Impairment: A Systematic Review.

Mild Cognitive Impairment (MCI) is a clinical syndrome characterized by a moderate decline in one or more cognitive functions with a preserved autonomy in daily life activities. MCI exhibits cognitive, behavioral, psychological symptoms. The executive functions (EFs) are key functions for everyday life and physical and mental health and allow for the behavior to adapt to external changes. Higher-level executive functions develop from basic EFs (inhibition, working memory, attentional control, and cognitive flexibility). They are planning, reasoning, problem solving, and fluid intelligence (Gf). This systematic review investigates the relationship between higher-level executive functions and healthy and pathological aging, assuming the role of executive functions deficits as a predictor of cognitive decline. The systematic review was conducted according to the PRISMA Statement. A total of 73 studies were identified. The results indicate that 65.8% of the studies confirm significant EFs alterations in MCI (56.8% planning, 50% reasoning, 100% problem solving, 71.4% fluid intelligence). These results seem to highlight a strong prevalence of higher-level executive functions deficits in MCI elderly than in healthy elderly.

Effect of vitamin D and other indicators of phosphorus-calcium metabolism on cognitive functions and quality of life in patients with Parkinson's disease

Parkinson’s disease (PD) is a multifactorial neurodegenerative disease. Consequently, there has been growing interest in identifying early preclinical disease symptoms and searching for their laboratory markers in recent decades.Objective: to studythe relationship between vitamin D levels, phosphorus-calcium metabolism and clinical manifestations of PD.Patients and methods. Serum levels of total vitamin D (VD), as well as total calcium, ionized calcium, alkaline phosphatase (AP), inorganic phosphorus, and parathyroid hormone (PTH) were assessed in 138 patients with PD. The severity of the disease was verified according to the Hoehn-Yar criteria, the clinical symptoms of the disease were verified using the Unified PD Rating Scale (UPDRS), the evaluation also included the quality of life (QoL) scales for patients with PD (PDQ-39), anxiety and depression (HADS), and Beck depression inventory, assessment of cognitive functions (CF) according to MoCA. Then, we analyzed the effect of vitamin D levels and other indicators of phosphorus-calcium metabolism on the severity of PD clinical symptoms.Results and discussion. Patients with PD had a significant impact of phosphorus-calcium metabolism on CF, assessed by MoCA scale and the PDQ-39 subscale “Cognitive functions”. A joint direct impact of vitamin D levels (β=0.111; p=0.002), PTH (β=0.02; p=0.037) and the indirect effect of AP (β=-0.028; p=0.027) on CF was revealed. A direct effect of the level of inorganic phosphorus (β=5.932; p=0.001) and AP (β=0.055; p=0.025) on the QoL of patients with PD was observed.Conclusion. Cognitive decline in PD patients is directly related to vitamin D and PTH levels. At the same time, the lower the QoL of patients with PD, the lower the serum vitamin D level was, serving as an early predictor of cognitive decline in patients with PD.

Anxiety, Depression, and Apathy as Predictors of Cognitive Decline in Patients With Parkinson's Disease-A Three-Year Follow-Up Study.

ObjectiveAnxiety, depression, and apathy are the most common neuropsychiatric symptoms in Parkinson's disease (PD) patients. They impair cognitive functioning and have a profound impact on quality of life. This follow-up study aims to investigate the predictive value of anxiety, depression, and apathy on the development of Mild Cognitive Impairment (MCI) in PD patients.MethodsTwenty-nine cognitively unimpaired PD patients (mean age 68.2 SD ± 7.12 years; 13 women) participated in this study. At Baseline (BL) levels of apathy (Apathy Evaluation Scale, AES), depression (Beck Depression Inventory, BDI-II), and anxiety (Beck Anxiety Inventory, BAI), were assessed. Cognitive status was reassessed three years later according to MCI/non-MCI status. For statistics, we used binary logistic regression and receiver operating characteristic curve (ROC) analysis to examine anxiety, apathy, and depression at BL as a predictor of MCI status three years later.ResultsEight of the 29 patients developed MCI. Anxiety level at BL was found to predict MCI status at three-year follow-up (OR = 1.20, CI = 1.02–1.41, p = 0.02), while depression (OR = 1.16, CI = 0.93–1.47, p = 0.20) and apathy (OR = 1.06, CI = 0.92–1.23, p = 0.40) did not predict MCI status. The area under the ROC curve (AUC) of BAI for discriminating PD-non-MCI from PD-MCI was 0.79 (CI = 0.61–0.98). The optimal classification threshold yielded a sensitivity of 75.0 % and a specificity of 76.2 %. Neither apathy nor depression at BL discriminated between PD-non-MCI patients from PD-MCI three years later.ConclusionsThis study shows an association between anxiety and the development of MCI in PD patients, although the association between apathy, depression, and MCI did not reach a significant level.

Impact of Small Vessel Disease Progression on Long-term Cognitive and Functional Changes After Stroke.

Background and ObjectivesThe severity of white matter hyperintensities (WMH) at presentation with stroke is associated with poststroke dementia and dependency. However, WMH can decrease or increase after stroke; prediction of cognitive decline is imprecise; and there are few data assessing longitudinal interrelationships among changing WMH, cognition, and function after stroke, despite the clinical importance.MethodsWe recruited patients within 3 months of a minor ischemic stroke, defined as NIH Stroke Scale (NIHSS) score <8 and not expected to result in a modified Rankin Scale (mRS) score >2. Participants repeated MRI at 1 year and cognitive and mRS assessments at 1 and 3 years. We ran longitudinal mixed-effects models assessing change in Addenbrooke’s Cognitive Examination–Revised (ACE-R) and mRS scores. For mRS score, we assessed longitudinal WMH volumes (cube root; percentage intracranial volume [ICV]), adjusting for age, NIHSS score, ACE-R, stroke subtype, and time to assessment. For ACE-R score, we additionally adjusted for ICV, mRS, premorbid IQ, and vascular risk factors. We then used a multivariate model to jointly assess changing cognition/mRS score, adjusted for prognostic variables, using all available data.ResultsWe recruited 264 patients; mean age was 66.9 (SD 11.8) years; 41.7% were female; and median mRS score was 1 (interquartile range 1–2). One year after stroke, normalized WMH volumes were associated more strongly with 1-year ACE-R score (β = −0.259, 95% CI −0.407 to −0.111 more WMH per 1-point ACE-R decrease, p = 0.001) compared to subacute WMH volumes and ACE-R score (β = 0.105, 95% CI −0.265 to 0.054, p = 0.195). Three-year mRS score was associated with 3-year ACE-R score (β = −0.272, 95% CI −0.429 to −0.115, p = 0.001). Combined change in baseline-1-year jointly assessed ACE-R/mRS scores was associated with fluctuating WMH volumes (F = 9.3, p = 0.03).DiscussionAfter stroke, fluctuating WMH mean that 1-year, but not baseline, WMH volumes are associated strongly with contemporaneous cognitive scores. Covarying longitudinal decline in cognition and independence after stroke, central to dementia diagnosis, is associated with increasing WMH volumes.

Emergency department point‑of-care predictors of cognitive decline and quality of life after spontaneous intracerebral hemorrhage

Introduction. Cognitive decline is a frequent consequence of stroke. This study aims to assess the contribution of admission point-of-care (POC) biomarkers to three-month cognitive decline and quality of life (QoL) in spontaneous intracerebral hemorrhage (sICH) patients. Materials and method. This prospective observational study included adult patients diagnosed with sICH within the first eight hours from symptom onset, over a period of 18 months. Medical history and clinical and paraclinical data were collected during the emergency department presentation (imagistics and POC biomarkers – complete blood count, glucose, renal and hepatic function). The follow-up included clinical assessment on the second and seventh days, a control computed tomography and telephone interviews on the 90th day. Results. All 35 enrolled patients reported alterations of quality of life. The quality of life was influenced by lymphocytes, platelets and D-dimer, with lymphocytes and D-dimer associated with mobility, self-care and ability to perform usual tasks. QoL related to pain/discomfort was influenced by D-dimer only. The median TICS-m was 23, with 13 (72.22%) evaluated participants reaching moderate cognitive impairment scores. Cognitive performance in general was influenced by mean platelets volume. Category fluency was not influenced by any parameter. Discussion. sICH leads to significant morbidity, with nearly 74% of all participants either dead or cognitively impaired on follow-up. Bearing in mind the simplicity of routinely obtaining POC inflammatory markers, future adequately sized studies should further explore their utility on predicting QoL and cognitive decline. Conclusions. Emergency department POC biomarkers could contribute to a timely estimation of cognitive impairment and QoL in sICH patients.

APOE4 Allele, Sex, and Dementia Risk in Parkinson's Disease: Lessons From a Longitudinal Cohort.

The effect of APOE4 allele on dementia risk is well established in Alzheimer's disease and Parkinson's disease (PD). However, it is unknown if sex modifies this relationship. We sought to determine the effect of sex on the relationship between APOE4 status and incident cognitive decline in PD. Data from the prospectively collected longitudinal National Alzheimer's Coordinating Center (NACC) Uniform Data Set (UDS) and Neuropathology Data Set (NDS) were analyzed. The NACC develops and maintains data from approximately 29 National Institutes of Aging-funded Alzheimer's Disease Research Centers. Further details may be found at the NACC web site (www.alz.washington.edu). The visit at which diagnosis of PD was made was termed the baseline visit. All patients with a PD diagnosis but without dementia at the baseline visit were included in the analyses. Presence of APOE4 allele was associated with higher odds (OR = 7.4; P < .001) of subsequent diagnosis of dementia and with a faster time to developing dementia (P = .04). Those with APOE4 allele were more likely to have neuropathology associated with Alzheimer's disease than those without APOE4 allele. We did not find any difference by sex. There were no differences between Lewy body pathology or neuron loss in the substantia nigra between the 2 groups. Sex was not associated with dementia risk in PD (OR = 0.53, P = .15) or with the time to dementia onset (P = .22). Sex did not modify the relationship between the APOE4 allele and dementia onset in PD patients (P = .12). APOE4 allele status in PD may be a predictor of cognitive decline in PD but does not appear to be modified by sex.

Social Disengagement and Cognitive Function: Does the Association Vary by Gender?

Although social disengagement is considered to be a predictor of cognitive decline, and increase risk of Alzheimer’s and related dementias, little is known regarding the gender-specific association between social disengagement and cognition among Korean middle-aged and older adults. Korea’s Confucianism-based gender roles provide unique contexts to examine gender differences in the influence of social disengagement on cognition. This study investigated the association between social disengagement and cognitive function in a nationally representative sample of Koreans aged 45 years or older (N = 5,196 women and 2,707 men), using data from the Korean Longitudinal Study of Aging (2008-2018). Results from the generalized estimating equation model showed that compared to consistent social engagement, consistent non-engagement was significantly associated with lower cognitive function among both genders. Transitioning from social engagement to non-engagement was significant for males only. Of various types of social activities (religious, senior center, sport, reunion, voluntary, political), consistent non-engagement in a senior center was most associated with lower cognitive function among both genders, while consistent non-engagement in religious activities was significant for females only. While household arrangements were not associated with cognition in men, widowed women had increased risk of cognitive decline than married women, as did women living in households of three or more people. Depression was a predictor of cognitive decline among males only. In this gender-specific study, we found that consistent participation in social activities, especially via membership in a senior community center, is beneficial in preventing cognitive decline among both genders.

Gait Speed and Grip Strength Are Predictors of Cognitive Decline and Dementia in Older Individuals.

Lower gait speed and grip strength are common in older adults. However, the results of lower motor function on cognitive outcomes have been mixed. We examined the longitudinal association between baseline slow gait speed and weak grip strength, alone and in combination, with risk of incident dementia or cognitive decline in a cohort of older adults. Participants (n=19,114) aged 70 and over (65 if U.S. minority) without documented evidence of dementia, significant cognitive impairment, physical disability or previous cardiovascular disease at baseline, were recruited from community settings. Incident dementia was adjudicated by an expert panel using DSM-IV criteria. Incident cognitive decline was defined as a persistent intra-individual decline in score of >1.5 SD from baseline on any of the cognitive tests. Using cox proportional hazard models, slow gait speed at baseline was associated with an increased risk of dementia (63%) and cognitive decline (43%), over a median 4.7 years. Weak grip strength was not as strong a predictor, but was also associated with risk (43% and 11%, respectively). Both outcomes showed higher risk for dementia than cognitive decline. There was no gender-specific interaction. When considered together (adjusted for one another), gait speed and grip strength were both independently associated with cognitive decline and dementia. The synergistic association of these physical measures, each of which is readily administered in the clinic or home, serve as effective early markers of increasing risk of cognitive decline and incident dementia and thus, should be considered for routine health assessments for older adults.

Neuropsychiatric Profile as a Predictor of Cognitive Decline in Mild Cognitive Impairment

Introduction: Mild cognitive impairment is often associated with affective and other neuropsychiatric symptoms (NPS). This co-occurrence might have a relevant impact on disease progression, from MCI to dementia.Objective: The aim of this study was to explore the trajectories of cognitive decline in an MCI sample from a memory clinic, taking into consideration a perspective of isolated cognitive functions and based on NPS clusters, accounting for the different comorbid symptoms collected at their baseline visit.Methods: A total of 2,137 MCI patients were monitored over a 2.4-year period. Four clusters of NPS (i.e., Irritability, Apathy, Anxiety/Depression and Asymptomatic) were used to run linear mixed models to explore the interaction of cluster with time on cognitive trajectories using a comprehensive neuropsychological battery (NBACE) administered at baseline and at the three subsequent follow-ups.Results: A significant interaction between cluster and time in cognitive decline was found when verbal learning and cued-recall were explored (p = 0.002 for both memory functions). For verbal learning, the Irritability cluster had the largest effect size (0.69), whereas the Asymptomatic cluster showed the smallest effect size (0.22). For cued-recall, the Irritability cluster had the largest effect size among groups (0.64), and Anxiety/Depression had the smallest effect size (0.21).Conclusions: In MCI patients, the Irritability and Apathy NPS clusters shared similar patterns of worsening in memory functioning, which could point to these NPS as risk factors of a faster cognitive decline, acting as early prognostic markers and helping in the diagnostic process.

An investigation of HCV as a predictor of cognitive decline: The Bio‐Hermes protocol

AbstractBackgroundA 2018 NIA‐AA Research Framework extended the biological definition of Alzheimer’s disease (AD) from biomarkers of amyloid (A) and tau (T) to include measures of neurodegeneration (N) thus enabling more detailed staging and identification of participants potentially closest to clinical decline (N+) (AlzheimersDement.2018;14(4):535‐562). This framework is only partially implemented in clinical trials as N is rarely considered a selection criterion. Hippocampal volume (HCV) measured from magnetic resonance imaging (MRI) has been proposed as a widely available, robust tool to define N+ (AlzheimersDement.2014;10(4):421‐429.e3).MethodParticipant selection through N+ will be validated in a sub‐study of the Bio‐Hermes trial planned by the Global Alzheimer’s Platform Foundation®. The Bio‐Hermes trial will assess biomarkers of Aβ, phospho‐tau, and neurofilament light in approximately 1,000 participants in three cohorts: cognitively normal, mild cognitive impairment, probable AD. A baseline MRI will be performed in approximately 200 additional participants randomized in a substudy. A pre‐defined HCV cut‐off from the Learning Embeddings for Atlas Propagation (LEAP) algorithm was identified to define N+ status (NeuroImage.2010;49(2):1316‐1325). The sub‐study will enrol participants willing to forgo treatment studies for 12 months to allow standardized measures of progression. Correlation with clinical measures and clinical decline will be compared in N+ and N‐ populations in the three cohorts to validate the benefit of full ATN staging in trial design.ResultWhile most publications using the LEAP algorithm for N+ AD patient stratification define N+ cut‐offs based on HCV percentiles in the analysed dataset (Neurobiology of Aging. 2012;33:2272–2281, Neurology. 2013;80(12):1124‐1132, , Neurology. 2016; 87(12):1235–124, Alzheimers Dement. 2018;14(7):1076, Alzheimers Dement. 2020; 10.1002/alz.037912), one study deployed percentiles from a healthy reference cohort (Neurobiology of Aging. 2014;35:808‐818). Based on prior work and simulations of the Bio‐Hermes trial cohorts, the N+ cut‐off was set at HCV=5.4cm3.ConclusionThe presented study design validates the use of MRI as inclusion criterion in AD clinical trials to fully implement ATN staging. As MRI is a standard tool during screening for AD clinical trials, additional participant characterisation can be achieved at minimal extra cost and burden, significantly improving trial power.