Lower MMSE Scores Research Articles

Multimorbidity patterns, leisure activities, and cognitive function: A population-based longitudinal study

Abstract Background There is limited knowledge about the effect of leisure activities on cognitive decline related to different multimorbidity patterns. The study aimed to examine the role of leisure activities in the association between multimorbidity patterns and cognitive function. Methods We conducted a community-based cohort study based on the 2002-2018 Chinese Longitudinal Health Longevity Survey (CLHLS). Multimorbidity patterns were examined by exploratory factor analysis. Multivariable linear and logistic regression models were used to assess the associations between multimorbidity, leisure activities and cognitive function. Results The study included 14,093 older adults. Those with specific multimorbidity patterns had lower MMSE scores. Compared to individuals with cardio-metabolic and sensory patterns who frequently engaged in activities such as housework, garden work, and watching TV/listening to the radio, those who participated in these activities less regularly had lower MMSE scores. Furthermore, a higher frequency change of participation and a greater variety of leisure activities were associated with better cognitive function. Conclusions The older individuals with multimorbidity are associated with lower MMSE scores, while those who participated in more leisure activities had higher cognitive function. Diverse, and frequent leisure activities may help delay cognitive decline in Chinese older adults with different multimorbidities.

Framingham Stroke Risk Profile Score and White Matter Disease Progression.

To evaluate the relationship between Framingham Stroke Risk Profile (FSRP) score and rate of white matter hyperintensity (WMH) progression and cognition. Consecutive patients enrolled in the Mayo Clinic Florida Familial Cerebrovascular Diseases Registry (2011-2020) with 2 brain-MRI scans at least 1 year apart were included. The primary outcome was annual change in WMH volume (cm 3 /year) stratified as fast versus slow (above vs. below median). Cognition was assessed using a Mini-Mental State Exam (MMSE, 0-30). FSRP score (0 to 8) was calculated by summing the presence of age 65 years or older, smoking, systolic blood pressure greater than 130 mmHg, diabetes, coronary disease, atrial fibrillation, left ventricular hypertrophy, and antihypertensive medication use. Linear and logistic regression analyses were performed to examine the association between FSRP and WMH progression, and cognition. In all, 207 patients were included, with a mean age of 60±16 y and 54.6% female. FSRP scores risk distribution was: 31.9% scored 0 to 1, 36.7% scored 2 to 3, and 31.4% scored ≥4. The baseline WMH volume was 9.6 cm 3 (IQR: 3.3-28.4 cm 3 ), and the annual rate of WMH progression was 0.9 cm3/year (IQR: 0.1 to 3.1 cm 3 /year). A higher FSRP score was associated with fast WMH progression (odds ratio, 1.45; 95% CI: 1.22-1.72; P<0.001) and a lower MMSE score (23.6 vs. 27.1; P<0.001). There was a dose-dependent relationship between higher FSRP score and fast WMH progression (odds ratios, 2.20, 4.64, 7.86, 8.03 for FSRP scores 1, 2, 3, and ≥4, respectively; trend P <0.001). This study demonstrated an association between higher FSRP scores and accelerated WMH progression, as well as lower cognition.

Multimorbidity measures associated with cognitive function among community-dwelling older Chinese adults.

Older adults with multimorbidity are at high risk of cognitive impairment development. There is a lack of research on the associations between different multimorbidity measures and cognitive function among older Chinese adults living in the community. We used the Chinese Longitudinal Healthy Longevity Survey from 2002 to 2018 and included data on dementia-free participants aged ≥65 years. Multimorbidity measures included condition counts, multimorbidity patterns, and trajectories. The association of multimorbidity measures with cognitive function was examined by generalized estimating equation and linear and logistic regression models. Among 14,093 participants at baseline, 43.2% had multimorbidity. Multimorbidity patterns were grouped into cancer-inflammatory, cardiometabolic, and sensory patterns. Multimorbidity trajectories were classified as "onset-condition," "newly developing," and "severe condition." The Mini-Mental State Examination scores were significantly lower for participants with more chronic conditions, with cancer-inflammatory/cardiometabolic/sensory patterns, and with developing multimorbidity trajectories. Condition counts, sensory pattern, cardiometabolic pattern, cancer-inflammatory pattern,and multimorbidity developmental trajectories were prospectively associated with cognitive function. Elderly individuals with a higher number of chronic conditions were associated with lower MMSE scores in the Chinese Longitudinal Healthy Longevity Survey data. MMSE scores were significantly lower for participants with specific multimorbidity patterns. Individuals with developing trajectories of multimorbidity were associated with lower MMSE scores and a higher risk of mild cognitive impairment.

Effect of Sacubitril/Valsartan on Cognitive Function in Patients With Heart Failure With Preserved Ejection Fraction: A Prespecified Analysis of PARAGON-HF.

A hypothetical concern has been raised that sacubitril/valsartan might cause cognitive impairment because neprilysin is one of several enzymes degrading amyloid-β peptides in the brain, some of which are neurotoxic and linked to Alzheimer-type dementia. To address this, we examined the effect of sacubitril/valsartan compared with valsartan on cognitive function in patients with heart failure with preserved ejection fraction in a prespecified substudy of PARAGON-HF (Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor With Angiotensin Receptor Blocker Global Outcomes in Heart Failure With Preserved Ejection Fraction). In PARAGON-HF, serial assessment of cognitive function was conducted in a subset of patients with the Mini-Mental State Examination (MMSE; score range, 0-30, with lower scores reflecting worse cognitive function). The prespecified primary analysis of this substudy was the change from baseline in MMSE score at 96 weeks. Other post hoc analyses included cognitive decline (fall in MMSE score of ≥3 points), cognitive impairment (MMSE score <24), or the occurrence of dementia-related adverse events. Among 2895 patients included in the MMSE substudy with baseline MMSE score measured, 1453 patients were assigned to sacubitril/valsartan and 1442 to valsartan. Their mean age was 73 years, and the median follow-up was 32 months. The mean±SD MMSE score at randomization was 27.4±3.0 in the sacubitril/valsartan group, with 10% having an MMSE score <24; the corresponding numbers were nearly identical in the valsartan group. The mean change from baseline to 96 weeks in the sacubitril/valsartan group was -0.05 (SE, 0.07); the corresponding change in the valsartan group was -0.04 (0.07). The mean between-treatment difference at week 96 was -0.01 (95% CI, -0.20 to 0.19; P=0.95). Analyses of a ≥3-point decline in MMSE, decrease to a score <24, dementia-related adverse events, and combinations of these showed no difference between sacubitril/valsartan and valsartan. No difference was found in the subgroup of patients tested for apolipoprotein E ε4 allele genotype. Patients with heart failure with preserved ejection fraction in PARAGON-HF had relatively low baseline MMSE scores. Cognitive change, measured by MMSE, did not differ between treatment with sacubitril/valsartan and treatment with valsartan in patients with heart failure with preserved ejection fraction. URL: https://www.clinicaltrials.gov; Unique identifier: NCT01920711.

Post-diagnostic support for persons with young-onset dementia – a retrospective analysis based on data from the Swedish dementia registry SveDem

BackgroundApproximately 3.9 million persons worldwide have young-onset dementia. Symptoms related to young-onset dementia present distinct challenges related to finances, employment, and family. To provide tailored support, it is important to gain knowledge about the formal support available for persons with young-onset dementia. Therefore, this paper aims to describe formal support for persons with young-onset dementia in Sweden and the factors influencing this support.MethodsThis retrospective study used data on persons under 65 years of age (n = 284) from The Swedish Registry for Cognitive/Dementia Disorders (SveDem) between 2021 and 2022. SveDem was established to monitor the quality of dementia care in Sweden. Characteristics of participants were obtained, including age, sex, dementia diagnosis, MMSE, medications, accommodation, and care setting. Descriptive statistics and logistic regression were used to test for associations between participant characteristics and post-diagnostic support.ResultsInformation and educational support were usually offered to the person with young-onset dementia (90.1%) and their family (78.9%). Approximately half of the sample were offered contact with a dementia nurse (49.3%), counsellor (51.4%), or needs assessor (47.9%). A minority (28.5%) were offered cognitive aids. Six regression models were conducted based on participant characteristics to predict the likelihood that persons were offered support. Support was not predicted by age, sex, children at home, accommodation, or medications. Lower MMSE scores (p < .05) and home help (p < .05) were significantly associated with offer of a needs assessor. Living together was a significant predictor (p < .01) for information and educational support offered to the family. Care setting significantly predicted (p < .01) an offer of information and educational support for the person and family members, as well as contact with a counsellor.ConclusionThis study indicates potential formal support shortages for persons with young-onset dementia in some areas of dementia care. Despite equal support across most characteristics, disparities based on care setting highlight the importance of specialised dementia care. Pre-diagnostic support is minimal, indicating challenges for persons with young-onset dementia to access these services before diagnosis. While our study has identified areas in need of improvement, we recommend further research to understand the changing support needs of those with young-onset dementia.

Prevalence and factors associated with dynapenia in elderly women in primary health care

Purpose: To analyze the prevalence and factors related to dynapenia in elderly women treated in primary health care, as well as compare anthropometric, metabolic and inflammatory parameters according to the determination of dynapenia. Methodology: A cross-sectional, quantitative study was carried out with elderly women at a Basic Health Unit in the Federal District. Sampling was carried out by convenience. Dynapenia was determined as a handgrip strength of less than 20 kilograms. Results: The elderly women had a mean age of 68.4 (± 6.2 years). Of the 200 elderly women studied, 113 had dynapenia (56.5%). Those with dynapenia had a higher age (P= 0.003), Il-6 (P=0.049) and time to perform the TUG (P&lt; 0.001), lower MMSE score (P= 0.019) and lower HRF (P= &lt;0.001) than those without dynapenia. No significant differences were observed for the metabolic variables (P&gt; 0.05). Conclusion: The study found a prevalence of dynapenia in 56.5% of the elderly women. No differences were observed in the metabolic pattern among the elderly women. Finally, impaired functional performance remained associated with a greater chance of the elderly presenting dynapenia.

Unraveling the interplay between dyskinesia and overactive bladder symptoms in Parkinson’s disease: a comprehensive cohort study based on the long-term follow-up database of Parkinson’s disease

ObjectivesOveractive bladder (OAB) and dyskinesia are frequent complications in patients with Parkinson’s disease (PD). However, the correlation between OAB and dyskinesia has been insufficiently explored. The purpose of this study was to examine the relationship between dyskinesia, OAB, and clinical characteristics among individuals with PD.Methods1338 PD patients were included in the present study. Demographic features were compared between patients with or without dyskinesia and OAB symptoms. Logistic regression was conducted on dyskinesia to screen clinically relevant factors. Overactive Bladder Symptom Score (OABSS) was further used to stratify the association between the severity of OAB and the occurrence of dyskinesia.ResultsThis study indicates that both dyskinesia and OAB are significantly related to disease severity and cognitive status. PD patients with dyskinesia and OAB having higher UPDRS scores (p < 0.001), H-Y scores (p < 0.001), NMSQ (p < 0.001) and MoCA scores (p < 0.001), and lower MMSE scores (p < 0.001) are identified. The multivariate logistic regression confirms that disease duration (p = 0.041), LEDD (p < 0.001), UPDRSII (p < 0.001), MoCA (p = 0.024), urgency (p < 0.001), frequency (p < 0.001), and nocturia (p = 0.002) are independent risk factors for dyskinesia. Trend analysis indicates that the risk of dyskinesia significantly increases when patients exhibit moderate to severe OAB symptoms (OABSS > 5) (p < 0.001). No significant interactions were found between OABSS and age, gender, disease duration, LEDD, and NMSQ scores in different subgroups, indicating that dyskinesia is more pronounced in patients with OABSS > 5.DiscussionThis study provides compelling evidence supporting the strong correlation between OAB and dyskinesia in PD patients, emphasizing the presence of shared pathogenic mechanisms between these two conditions. Our findings underscore the importance of considering both OAB and dyskinesia in the clinical management of PD, investigating the intricate connections between OAB and dyskinesia could unveil valuable insights into the complex pathophysiology of PD and potentially identify novel therapeutic targets for more effective PD treatment strategies.

Anosognosia is associated with increased prevalence and faster development of neuropsychiatric symptoms in mild cognitive impairment.

Both the loss of awareness for cognitive decline (a. k.a anosognosia) and neuropsychiatric symptoms (NPS) are common in patients with Alzheimer's disease (AD) dementia, even in prodromal stages, and may exacerbate functional impairment and negatively impact caregiver burden. Despite the high impact of these symptoms on patients and their caregivers, our knowledge of how they develop across the AD spectrum is limited. Here, we explored the cross-sectional and longitudinal associations between anosognosia and NPS in individuals with mild cognitive impairment (MCI). We included 237 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) with a baseline clinical diagnosis of MCI. Everyday Cognition (ECog) questionnaire scores were used to measure complaints from participants and study-partners at baseline and annually over a mean of 4.29 years [standard deviation (SD) = 2.72]. Anosognosia was defined as the study-partner having an ECog score ≥2.5/4 and the participant having an ECog score < 2.5/4 on their baseline measure and their last observation without more than two consecutive deviating observations during the follow-up period. The 12-item study-partner-rated Neuropsychiatric Inventory determined the presence or absence of specific NPS. Survival analyses were performed to analyze the frequency and temporal onset of NPS over time in individuals with and without anosognosia. Thirty-eight out of 237 participants displayed anosognosia. Groups had similar lengths of follow-up at baseline (p > 0.9), though participants with anosognosia had lower MMSE scores (p = 0.049) and a higher proportion of amyloid-positivity using PET (p < 0.001. At baseline, the frequencies of agitation (p = 0.029) and disinhibition (p < 0.001) were higher in the anosognosia group compared to the non-anosognosia group. Survival analyses showed earlier onset of seven of the 12 NPS in the anosognosia group (p's < 0.001). Loss of awareness for cognitive decline is associated with greater frequency and earlier onset of NPS over time in participants with MCI. These results support the hypothesis of a potential common underlying neurophysiological process for anosognosia and NPS, a finding that needs to be addressed in future studies.

In vivo microstructural heterogeneity of white matter and cognitive correlates in aging using tissue compositional analysis of diffusion magnetic resonance imaging.

Age-related cognitive decline is linked to changes in the brain, particularly the deterioration of white matter (WM) microstructure that accelerates after the age of 60. WM deterioration is associated with mild cognitive impairment and dementia, but the origin and role of white matter signal abnormalities (WMSA) seen in standard MRI remain debated due to their heterogeneity. This study explores the potential of single-shell 3-tissue constrained spherical deconvolution (SS3T-CSD), a novel technique that models diffusion data in terms of gray matter (TG ), white matter (Tw ), and cerebrospinal fluid (TC ), to differentiate WMSA from normal-appearing white matter and better understand the interplay between changes in WM microstructure and decline in cognition. A total of 189 individuals from the GENIC cohort were included. MRI data, including T1-weighted and diffusion images, were obtained. Preprocessing steps were performed on the diffusion MRI data, followed by the SS3T-CSD. WMSA were segmented using FreeSurfer. Statistical analyses were conducted to assess the association between age, WMSA volume, 3-tissue signal fractions (Tw , TG , and TC ), and neuropsychological variables. Participants above 60 years old showed worse cognitive performance and processing speed compared to those below 60 (p < .001). Age was negatively associated with Tw in normal-appearing white matter (p < .001) and positively associated with TG in both WMSA (p < .01) and normal-appearing white matter (p < .001). Age was also significantly associated with WMSA volume (p < .001). Higher processing speed was associated with lower Tw and higher TG , in normal-appearing white matter (p < .01 and p < .001, respectively), as well as increased WMSA volume (p < .001). Similarly, lower MMSE scores correlated with lower Tw and higher TG in normal-appearing white matter (p < .05). High cholesterol and hypertension were associated with higher WMSA volume (p < .05). The microstructural heterogeneity within normal-appearing white matter and WMSA is associated with increasing age and cognitive variation, in cognitively unimpaired individuals. Furthermore, the 3-tissue signal fractions are more specific to potential white matter alterations than conventional MRI measures such as WMSA volume. These findings also support the view that the WMSA volumes may be more influenced by vascular risk factors than the 3-tissue metrics. Finally, the 3-tissue metrics were able to capture associations with cognitive tests and therefore capable of capturing subtle pathological changes in the brain in individuals who are still within the normal range of cognitive performance.

Microglia measured by TSPO PET are associated with Alzheimer's disease pathology and mediate key steps in a disease progression model.

Evidence suggests microglial activation precedes regional tau and neurodegeneration in Alzheimer's disease (AD). We characterized microglia with translocator protein (TSPO) positron emission tomography (PET) within an AD progression model where global amyloid beta (Aβ) precedes local tau and neurodegeneration, resulting in cognitive impairment. Florbetaben, PBR28, and MK-6240 PET, T1 magnetic resonance imaging, and cognitive measures were performed in 19 cognitively unimpaired older adults and 22 patients with mild cognitive impairment or mild AD to examine associations among microglia activation, Aβ, tau, and cognition, adjusting for neurodegeneration. Mediation analyses evaluated the possible role of microglial activation along the AD progression model. Higher PBR28 uptake was associated with higher Aβ, higher tau, and lower MMSE score, independent of neurodegeneration. PBR28 mediated associations between tau in early and middle Braak stages, between tau and neurodegeneration, and between neurodegeneration and cognition. Microglia are associated with AD pathology and cognition and may mediate relationships between subsequent steps in AD progression.

Vitamin B6 and vitamin D deficiency co-occurrence in geriatric memory patients.

Vitamin B6 and D levels are not assessed routinely in geriatric memory patients. This study examined vitamin levels to determine the potential effects on cognition. A chart review was conducted of 203 consecutive patients over a 12-month period. Levels of vitamins B1, B6, B12, and D were obtained on the day of clinic to identify deficiencies. A mental status exam (Mini Mental State Examination [MMSE]) was also performed. One hundred sixty-seven patients had one or more vitamin levels obtained on the day of clinical evaluation. Vitamin B6 deficiency was the most common (37.5%), followed by vitamin D deficiency (36.8%). A chi-square test revealed significant co-occurrence of deficiency of vitamins B6 and D (p<0.001). Vitamin B6 and D deficiencies were associated with lower MMSE scores (p<0.05). Vitamin B6 and D deficiencies are common in geriatric patients. The coexistence of these vitamin deficiencies has a significant association with cognitive performance, indicating the clinical importance of monitoring and supplementation.

Early Benefits with Potential Long-Term Risks of a Comprehensive Intervention on Serum Cortisol Levels and Cognitive Performance in Patients with Alzheimer's Disease.

Elevated cortisol levels represent a risk factor for Alzheimer's disease (AD), prompting treatments to lower hormone concentrations for preventive or therapeutic purposes. To assess the efficacy of a comprehensive intervention (CI) in modulating serum cortisol levels in patients with AD. CI consisted in a 2-month protocol involving cognitive stimulation, psychological support, lifestyle guidance, leisure activities, and socialization. AD subjects were randomly assigned to experimental (EG, n = 45) and control (CG, n = 45) groups. A wide range of sociodemographic, cognitive, psychosocial, and functional conditions were evaluated before, at the conclusion, and 24 months after CI. Data about lifestyle and drug prescription were also recorded. Baseline evaluations revealed that higher cortisol levels correlated with worse cognitive status (higher CDR and ADAS-Cog values and lower MMSE scores), increased depressive symptoms, and reduced physical and social engagement. Following CI, EG exhibited reduced cortisol levels, improved overall cognitive status, and enhanced verbal working memory and executive functions compared to CG. However, at the 24-month follow-up, EG displayed a rebound effect, characterized by elevated cortisol levels and cognitive decline compared to CG. These findings strengthen the adverse relationship between excessive cortisol and deficits in cognition/behavior in AD, demonstrate the short-term benefits of CI, and emphasize the potential long-term risks, which may be attributed to the fragile nature of the AD brain. Comprehensive interventions can yield positive results, but careful calibration of type and duration is necessary, considering disease progression and the potential need for re-administration.

Cognitive functioning and psychosomatic syndromes in a subjective tinnitus sample.

Tinnitus is the perception of a sound in the absence of any corresponding external sound source. Current research suggests a relationship among emotional, cognitive, and psychosomatic symptoms and the occurrence or maintenance of chronic tinnitus. This study aimed to detect the prevalence and role of psychosomatic conditions, as defined by the Diagnostic Criteria for Psychosomatic Research (DCPR), and cognitive functioning in a group of patients with tinnitus. Sixty-two patients with subjective tinnitus and 62 non-tinnitus controls were recruited from the Otorhinolaryngology Unit of the University of Bari. Pure-tone audiometry was performed in all tinnitus subjects, and sound level tolerance was evaluated. Additionally, tinnitus handicap (Tinnitus Handicap Inventory [THI]), psychopathological symptoms (Symptom Checklist-90, Revised [SCL-90-R]), anxiety (State-Trait Anxiety Inventory [STAI-Y1/2]), depression (Beck Depression Inventory [BDI]), cognitive impairment (Mini-Mental State Examination [MMSE]), executive functions (Frontal Assessment Battery [FAB]), and psychosomatic syndromes (DCPR) were evaluated. Parametric and non-parametric tests were used to detect cognitive and symptomatological differences between patients and controls. The predictivity of these factors for tinnitus severity was studied using multiple regression (Backward Elimination). All tests were considered significant at p < 0.05 (family wise error corrected for each comparison). 69.4% tinnitus patients met multiple DCPR criteria, compared to 32.3% of controls. Tinnitus patients exhibited elevated rates of illness denial (ꭓ2 = 9.02; p < 0.009), demoralization (ꭓ2 = 8.05; p < 0.018), somatization (ꭓ2 = 4.92; p < 0.063) and functional symptoms (ꭓ2 = 5.21; p < 0.06) scoring significantly higher on the BDI, STAI-Y1, and STAI-Y2, and SCL-90-R compared to controls. Patients with tinnitus showed lower MMSE scores, compared to controls (t = -2.282; p < 0.001). No association between tinnitus severity and global cognitive impairment emerged. Conversely, executive function deficits were associated to tinnitus severity. Among the cognitive and psychological factors, only trait anxiety, one or more psychosomatic syndromes, and somatization clusters were strongly correlated with tinnitus severity. Our findings suggest a relationship between tinnitus severity, psychological, psychosomatic symptoms, and frontal impairment. Additionally, the influence of tinnitus on cognitive functions paves the way for integrated, multidisciplinary diagnostic and treatment options for patients. Although preliminary, our findings highlight the importance of early cognitive and psychological screening to improve patients' quality of life.

Levels of plasma ADAM10 and cognitive performance in older adults with and without Alzheimer’s dementia from a middle‐income country

AbstractBackgroundAlzheimer’s Disease (AD) is the most prevalent dementia, and its underdiagnosis rates are still challenging, especially in low and middle‐income countries (LMIC) (Pelegrini et al., 2019). Research suggests the potential benefits of blood‐based biomarkers for accurate diagnosis, and ADAM10 is an example (Oliveira et al., 2020). However, more evidence from LMIC, such as Brazil and other Latin American countries, is necessary (Parra et al., 2022).AimTo compare the plasma ADAM10 levels and cognitive performance between healthy older adults and individuals with AD in a Latin American country.MethodsThis is a cross‐sectional study in which healthy older adults (n = 31) and participants with AD (n = 51) had their cognitive performance assessed through MMSE. In addition, a blood sample was collected, and the plasma ADAM10 levels were obtained through SDS‐PAGE and Western‐Blotting analyses. Comparison of means, correlation, and binomial logistic regression analyses were conducted at a significance level of p&lt;0.05.ResultsMost participants were female (61%), whose average age was 76.1 (8.3). The mean years of education and MMSE scores were, respectively, 4.6 (4.1) and 18.8 (8.2). The AD group was older (U = 363.5; p&lt;0.001); had a lower score on MMSE (U = 129; p&lt;0.001), and had higher plasma ADAM10 levels (U = 429; p = 0.001). Correlation analysis revealed a relationship between MMSE score and ADAM10 levels (r = ‐0.225; p = 0.04); age and cognitive performance (r = ‐0.353; p = 0.001); as well as between age and ADAM10 levels (r = 0.324; p = 0.004). Finally, our results suggested that those individuals with higher plasma ADAM10 levels have approximately eleven times more chances of being diagnosed with AD (B = 2.36; S.E. = 0.74; p = 0.001; Exp(B) = 10.63; 95%CI [2.48 – 45.69]).ConclusionThis study showed that levels of ADAM10 are different between healthy older adults and individuals with AD. Specifically, participants with AD have higher plasma ADAM10 levels. Also, low MMSE scores were correlated with higher ADAM10 plasma levels. Finally, people with higher plasma ADAM10 levels have more chances of being diagnosed with AD.

Association of Polygenic Risk Score of Alzheimer’s disease with A/T/N Biomarkers and Cognitive Decline

AbstractBackgroundPolygenic risk scores (PRS) quantify the combined effects of genetic variants to enable the prediction of an individual’s risk of developing the disease. Alzheimer’s disease (AD) is a complex disorder in which the relationship among PRS, neuropathological substrates, and related cognitive decline remain especially understudied in Asian populations. We investigated the associations of PRS with AD neuroimaging biomarkers and cognitive phenotypes in a Korean Cohort.MethodThe study included 501 older adults (264 cognitively normal [CN], 146 mild cognitive impairment [MCI], and 91 AD dementia) from the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer’s Disease (KBASE). Comprehensive clinical and neuropsychological evaluations, as well as multi‐modal neuroimaging including 3T MRI and 11C‐PiB‐PET were administered. A subset of participants underwent 18F‐AV‐1451 PET (n = 167). Imaging phenotypes including beta‐amyloid (Aβ) positivity, global tau deposition, and adjusted hippocampal volume (HVa) were used for amyloid (A), tau (T), and neurodegeneration (N) biomarkers, respectively., which was imputed using the TOPMed reference panel. PRS was calculated using the summary statistics of a recent large‐scale GWAS study for AD by PRS‐CS. The Apolipoprotein E (APOE) region was excluded in the calculation. The associations between standardized PRS and imaging/cognitive phenotypes were examined using either multiple linear or logistic regression analysis with covariates (age and sex for neuroimaging biomarker phenotypes; age, sex and education for cognitive phenotypes).ResultPRS was significantly higher in the AD dementia group compared to the CN group. Higher PRS was associated with greater CDR‐sum‐of‐boxes (β[SE] = 0.233[0.083], t = 2.818, p = 0.005) and lower MMSE scores (β[SE] = ‐0.648[0.198], t = ‐3.271, p = 0.001). In terms of AD neuroimaging biomarkers (Figure 1), higher PRS was significantly associated with an increased likelihood of Aβ positivity (OR = 1.233, 95%CI = 1.024‐1.491), and lower HVa (β[SE] = ‐132.79[49.624], t = ‐2.676, p = 0.008), but not with global tau deposition (β[SE] = 0.075[0.048], t = 1.573, p = 0.118).ConclusionThese findings suggest that higher PRS predicts increased pathological Aβ deposition and accelerated neurodegeneration, as well as greater cognitive decline. Further investigation in larger and multiethnic samples are needed to determine generalizability to other ethnoracial populations.

Longitudinal effects of sex on pathology accumulation, neurodegeneration and cognitive decline in Presenilin‐1 E280A mutation carriers: preliminary findings from the Colombia‐Boston (COLBOS) biomarker study

AbstractBackgroundPrevious work showed that females at risk for autosomal dominant Alzheimer’s disease (AD) due to a single mutation (E280A) in the Presenilin‐1 gene (PSEN1) may have greater cognitive resilience to AD‐pathology and neurodegeneration than males. However, more research is needed to clarify the effect of sex on AD risk and progression. We investigated the effects of sex on rates of amyloid and tau accumulation, neurodegeneration, and memory decline in PSEN1 mutation carriers with and without cognitive impairment, who are genetically determined to develop early‐onset dementia.MethodA total of 66 cognitively unimpaired mutation carriers (mean age of 34.41 +/‐ 4.86 years; 38 females), and 23 cognitively impaired mutation carriers (mean age of 44.91 +/‐ 2.83 years; 17 females) from the Colombia‐Boston Biomarker (COLBOS) study completed baseline cognitive assessments. A subset of 52 participants also completed florbetapir‐ and flortaucipir‐PET, and structural MRI. Cognitive and neuroimaging follow‐up visits were completed at 2‐ (n = 29) and 4‐year (n = 13) intervals. We used linear mixed‐effects models, with random intercepts, to predict rate of change in MMSE scores, CERAD word list delayed recall, cortical amyloid burden, tau in the entorhinal, inferior temporal, and precuneus cortices, and hippocampal volume by sex, controlling for education.ResultOver time, carriers exhibited greater cortical amyloid burden (p&lt;.001), inferior temporal tau (p = .019), precuneus tau (p = .003), lower hippocampal volume (p = .005), and showed a trend towards lower MMSE scores (p = .059) and word list delayed recall (p&lt;.080); entorhinal tau did not significantly increase (p = .137). Female carriers showed a steeper decline in word list delayed recall than male carriers (p = .021). There were no sex differences in the rate of accumulation of mean cortical amyloid or regional tau, hippocampal atrophy, or change in MMSE scores (all ps&gt;.05).ConclusionPreliminary findings of this ongoing study suggest that despite similar rates of pathology accumulation or atrophy between female and male PSEN1 E280A carriers, female mutation carriers may have faster memory decline. Future analyses with additional participants and follow‐up intervals are needed to characterize sex differences in ADAD risk and resilience, as well as inform development of treatments and interventions.

Functionality and socio‐demographic factors in chilean’s community‐dwelling elderly with subjective cognitive complaints . The GERO Cohort

AbstractBackgroundSubjective cognitive complaints (SCCs), defined as cognitive concerns of people who may or may not have deficits in objective, is considered a predictor for cognitive and functional decline and incident to dementia risk of progression to dementia. SCC is a heterogeneous condition associated. Most of the studies have been carried out in populations other than those of Latin America. The objective of this study was to analyze the socio‐demographic and functional profile in SCC elderly with and without cognitive impairment.MethodThe GERO cohort is a prospective cohort study of community‐dwelling elderly with SCC, without dementia, aged 70 or older living in Santiago, Chile. Participants were identified by a household census and information on demographics, biomedical, psychosocial, neuropsychological, neuropsychiatric, and motor function were collected by means of questionnaires and evaluations. Montreal Cognitive Assessment (MOCA) was used to compare individuals with and without cognitive impairment (MOCA score ≤ 21 and &gt; 21 respectively). Functionality was measured with the Pfeffer Functional Activities Questionnaire (FAQ) and Technology Activities of Daily Living Questionnaire (T‐ADLQ) that yield a global score and score by domain of activities of daily living (ADL), i.e basic (BADL), instrumental (IADL), and advanced ADL (a‐ADL).ResultFrom May 2017 to December 2020, a total of 17,759 households were successfully approached, identifying 2,533 eligible subjects, of which 299 individuals were included. After evaluation, 7 individuals were excluded for different reasons and 291 individuals were analyzed, female 80% (n = 243). The age of the individuals was 76.8 ± 5 years old, 60% of the participants were older than 75 years old. Participants with cognitive impairment compared to those without it were older (p = 0.003), with lower education years (p = &lt;0.001), lower income (p = 0.036), lower MMSE score (p = &lt;0.001), decline in a‐ADL (p = 0.006) and with more hypertension prevalence (p = 0.009)ConclusionFew other studies addressed cognitive complaint and functionality decline in recruited elderly at home. Older adults with cognitive impairments are characterized by less years of education, income, poor functionality and more comorbidities. Future multidimensional and prospective analysis of this cohort could bring more information about this association.

Survival and pharmacotherapy delay in young onset Alzheimer’s disease

AbstractIntroductionSpecific feature of young onset Alzheimer’s disease (YOAD) patients is that their diagnosis and therefore their treatment is usually delayed. Firstly, they present atypically, secondly, they have a higher cognitive reserve and symptoms are later recognized and finally at that age, the family, and the patients themselves, do not think about the possibility of dementia, which prolongs the time period to seeking medical help (on average 2‐3 years).AimTo examine the association of survival in YOAD with time elapsed from the onset of symptoms to the initiation of pharmacotherapy.Material and methodsThis is a retrospective study on 135 patients from Memory Center of Neurology Clinic, Clinical Center of Serbia, with clinical diagnosis of YOAD. We included outpatients that had first visit to our clinic from 01.04.2012. do 01.04.2017. The association of survival with time elapsed from onset of symptoms to initiation of therapy was examined by Kaplan Meier survival analysis with log rank test.ResultsFrom 2012, when the registry was created, till 2019, 89 out of 135 included patients died. Kaplan Meier survival analysis showed that patients with lower MMSE score (from 15 points and below) and who could not dress themselves or perform personal hygiene at the time of inclusion in our registry have a shorter expected survival than those who had MMSE 16 and above (p = 0.019) and who functioned independently in terms of these activities of daily living (p = 0.041 for dressing and p = 0.018 for performing personal hygiene). Patients in whom the introduction of therapy was delayed 3 or less years survived for a year longer than patients in whom therapy was introduced 4 or more years after the onset of dementia symptoms (p = 0.004).ConclusionOur study clearly showed that certain clinical parameters (degree of cognitive and functional damage at the time of therapy introduction), but also delay in introducing therapy from symptoms onset determine the length of survival in YOAD.

Impact of diabetes and glycated hemoglobin level on the clinical manifestations of Parkinson's disease

BackgroundThe coexistence of diabetes mellitus (DM) has been suggested to accelerate the progression of Parkinson's disease (PD) and make the phenotype more severe. In this study, we investigated whether DM or glycated hemoglobin (HbA1c) levels affect the differences in motor and nonmotor symptoms. MethodsWe conducted a cross-sectional study including 140 consecutive Japanese patients with PD for whom medical history and serum HbA1c records were available. The PD patients with a DM diagnosis were classified into the diabetes-complicated group (PD-DM) and the nondiabetes-complicated group (PD-no DM). Next, patients were classified based on a median HbA1c value of 5.7, and clinical parameters were compared. The correlations between HbA1c levels and other clinical variables were analyzed. ResultsOf 140 patients, 23 patients (16%) had DM. Compared to PD-no DM patients, PD-DM patients showed lower MMSE scores. Compared to the lower HbA1c group, the higher HbA1c group showed a higher MDS-UPDRS part III score and a lower metaiodobenzylguanidine (MIBG) scintigraphy heart-to-mediastinum (H/M) ratio. HbA1c levels were positively correlated with age and the MDS-UPDRS part III score and negatively correlated with the MMSE score and H/M ratio on cardiac MIBG scintigraphy. Binary logistic regression analysis, which included age, sex, disease duration, and MMSE and MDS-UPDRS part III scores as independent variables, revealed that a lower MMSE score was an independent contributor to PD-DM and PD with high HbA1c levels. ConclusionsDM complications and high HbA1c levels may affect cognitive function in patients with PD.

31 Machine Learning Algorithm to Predict Duration to Full Time Care after Alzheimer's Disease Diagnosis

Objective:Patients and their families often ask clinicians to estimate when full-time care (FTC) will be needed after Alzheimer's Disease (AD) is diagnosed. Although a few algorithms predictive algorithms for duration to FTC have been created, these have not been widely adopted for clinical use due to questions regarding precision from limited sample sizes and lack of an easy, user friendly prediction model. Our objective was to develop a clinically relevant, data-driven predictive model using machine learning to estimate time to FTC in AD based on information gathered from a) clinical interview alone, and b) clinical interview plus neuropsychological data.Participants and Methods:The National Alzheimer's Coordinating Center dataset was used to examine 3,809 participants (M age at AD diagnosis = 76.05, SD = 9.76; 47.10% male; 87.20% Caucasian) with AD dementia who were aged &gt;50 years, had no history of stroke, and not dependent on others for basic activities of daily living at time of diagnosis based on qualitative self or informant report. To develop a predictive model for time until FTC, supervised machine learning algorithms (e.g., gradient descent, gradient boosting) were implemented. In Model 1, 29 variables captured at the time of AD diagnosis and often gathered in a clinical interview, including sociodemographic factors, psychiatric conditions, medical history, and MMSE, were included. In Model 2, additional neuropsychological variables assessing episodic memory, language, attention, executive function, and processing speed were added. To train and test the algorithm(s), data were split into a 70:30 ratio. Prediction optimization was examined via cross validation using 1000 bootstrapped samples. Model evaluation included assessment of confusion matrices and calculation of accuracy and precision.Results:The average time to requiring FTC after AD diagnosis was 3.32 years (Range = 0.53-14.57 years). For the clinical interview only model (Model 1), younger age of onset, use of cholinesterase inhibitor medication, incontinence, and apathy were among the clinical variables that significantly predicted duration to FTC, with the largest effects shown for living alone, a positive family history of dementia, and lower MMSE score. In Model 2, the clinical predictors remained significant, and lower Boston Naming Test and Digit-Symbol Coding scores showed the largest effects in predicting duration to FTC among the neuropsychological measures. Final prediction models were further tested using five randomly selected cases. The average estimated time to FTC using the clinical interview model was within an average of 5.2 months of the recorded event and within an average of 5.8 months for the model with neuropsychological data.Conclusions:Predicting when individuals diagnosed with AD will need FTC is important as the transition often carries significant financial costs related to caregiving. Duration to FTC was predicted by clinical and neuropsychological variables that are easily obtained during standard dementia evaluations. Implementation of the model for prediction of FTC in cases showed encouraging prognostic accuracy. The two models show promise as a first step towards creation of a user friendly prediction calculator that could help clinicians better counsel patients on when FTC after AD diagnosis may occur, though the development of separate models for use in more diverse populations will be essential.