Cognitive Examination Research Articles

A Case of Personality and Behavioral Changes with Frontotemporal and Cerebellar Atrophy on MRI with Corresponding Hypometabolism on FDG‐PET

Background. The differential diagnosis of a patient with cognitive, behavioral, and motor symptoms is broad. There is much overlap between neurocognitive disorders due to frontotemporal dementia and other subcortical dementia. A less known diagnosis, cerebellar cognitive affective syndrome (CCAS), should also be considered. Case History. A 29‐year‐old female presented with ataxia and left‐sided weakness. CSF showed oligoclonal bands, and MRI showed multiple white matter lesions with some atrophy. She was diagnosed with multiple sclerosis (MS). At age 35, she developed frontal lobe symptoms and executive dysfunction; she was diagnosed with MS with bipolar disorder. Neuropsychological evaluation at that time showed significant deficits in multiple cognitive domains. Subsequent MRI showed progressive frontotemporal atrophy, and FDG‐PET uncovered hypometabolism in the frontotemporal lobes and cerebellum. At age 38, her behavior worsened with aggression, and she was started on olanzapine. She responded well with decreased agitation and improved motivation and attention. Compared with previous scans, most recent MRI and FDG‐PET showed interval increase in cerebellar atrophy with increase in hypometabolism in the cerebellum, respectively. Conclusion. Based on cerebellar, affective, and subcortical cognitive examination findings, our diagnosis is probable CCAS. The cerebellum should be considered as a possible etiology of frontal subcortical cognitive impairment.

Efficacy of Simultaneous Application of Repetitive Transcranial Magnetic Stimulation and Virtual Reality Training on Sensory-motor and Cognitive Deficits among Stroke Patients: A Protocol for a Randomised Controlled Trial

Introduction: Stroke is a significant contributor to chronic impairment on a global scale, impacting millions of individuals each year. Despite the progress made in the field of stroke management, individuals frequently experience enduring sensorimotor and cognitive impairments that have a substantial influence on their quality of life and ability to live independently. Need of the study: Virtual Reality Training (VRT) consists of rigorous, repetitive sessions that promote cerebral-hemispheric integration through the creation of a stimulating environment that combines sensory and motor functions. It is anticipated that VRT and Transcranial Magnetic Stimulation (TMS) will stimulate the affected hemisphere while inhibiting the unaffected hemisphere. Voluntary movement is also crucial for interhemispheric interaction; therefore, the present research employs VRT for physical movements while stimulating across multiple regions of the brain. Aim: To investigate the combined efficacy of Repetitive Transcranial Magnetic Stimulation (rTMS) and Virtual Reality Training for sensorimotor and cognitive deficits among stroke patients. Materials and Methods: The present study will be a singleblind, prospective, randomised controlled trial recruiting 69 patients with unilateral stroke from Jaypee Hospital Noida, Uttar Pradesh, India for a continuous period of one year from July 2023 to June 2024 and will be allocated through block randomisation to one of the three treatment groups as per the inclusion and exclusion criteria. Group 1- Simultaneous repetitive TMS (rTMS) and VRT, Group 2- rTMS combined with Sham VRT, and Group 3- VRT protocol combined with Sham Stimulation. Fugl Meyer Assessment (FMA), Montreal Cognitive Assessment (MOCA), National Institutes of Health Stroke Scale (NIHSS), and Addenbrooke’s Cognitive Examination III (ACE III) will be measured at baseline and at the end of the fourth week.

Accuracy of the revised Addenbrooke Cognitive Examination (ACE-R) in older adults with low education and mild cognitive impairment: results of a cross-sectional study in two metropolitan areas of Northeast Brazil

Accuracy of the revised Addenbrooke Cognitive Examination (ACE-R) in older adults with low education and mild cognitive impairment: results of a cross-sectional study in two metropolitan areas of Northeast Brazil

Cognitive functioning of a patient with herpes simplex virus encephalitis – a case study. An exemplary paper for the State Examination in the field of clinical psychology – neuropsychology

This paper is an example of a case report for a state examination in the field of clinical psychology – neuropsychology. The case report was used during the examination in 2023 and received a positive rating. Its publication is an attempt to respond to the still reported difficulties in accessing exemplary works of this type. Due to publication limitations, some elements of the description have been shortened. The article can also be treated as a case study on the cognitive functioning of a person with active herpes encephalitis. Both screening scales, such as Addenbrooke’s Cognitive Examination III and Frenchay Aphasia Screening Test, as well as other scales to measure individual cognitive functions were used in order to assess the patient.

Evidence of validity and reliability of the Colombian version of Addenbroke’s Cognitive Examination Revised (ACE-R)

Objective The purpose of this study is to provide evidence that supports the validity and reliability of the Colombian version of the Addenbrooke’s Cognitive Examination Revised (ACE-R) in comparison to the MMSE at assessing and finding patients with Mild Cognitive Impairment (MCI). Additionally, the study aims to determine the optimal cut-off scores based on the age of a population with a low education level. Method This study included 314 individuals (235 participants diagnosed with MCI and 79 cognitively healthy) who live in two different rural departments (states) in Colombia. The participants were recruited for this study through community clubs for the older adults. Most of the individuals were female (236), the average age was 65.95 years of age (SD= 7.8), and the average education level was of 3.78 years (SD = 1.79). It is important to note that the sample only included people with a maximum of 6 years of schooling. Results A ROC analysis indicated that the ACE-R is more effective than the MMSE at evaluating and finding MCI individuals within the three groups. The cut-off points for the Under 60 years of age group was 83.50 (sensitivity 0.880% and specificity 0.632%); 61–69 years of age 80.50 (sensitivity 0.714% and specificity 0.677%); and Over 70 years of age was 79.50 (sensitivity 0.750% and specificity 0.659%). The internal consistency analysis with MacDonald’s Ω determined reliability indicators ≥70 in the ACE-R, except for the age range of 61 to 69 years. Conclusion The Colombian version of the ACE-R demonstrates to be a valid and reliable global cognitive screening tool. It is effective at discerning MCI individuals from healthy within a group of participants with a low education level.

MULTIMORBIDITY PATTERNS AND COGNITIVE CHANGE AMONG MEXICAN OLDER ADULTS IN THE MEXICAN HEALTH AND AGING STUDY

Abstract Multimorbidity (≥ 2 chronic conditions) increases the risk of non-normative cognitive decline. Among Mexican older adults, little is known about 1) the prevalence of multimorbidity, 2) patterns of multimorbidity, and 3) the relationship between multimorbidity patterns and cognitive decline. We used representative data from the Mexican Health and Aging Study to estimate prevalence of multimorbidity, identify common multimorbidity patterns, and examine associations between multimorbidity patterns and cognitive change from 2012–2015 in Mexican adults aged ≥ 65 (n=5,079; mean age: 72.2 (SD=6.1)). Chronic conditions including hypertension, diabetes, cancer, lung disease, heart attack, stroke, and arthritis were measured in 2012, and cognitive function was assessed in 2012 and 2015 using the Cross Cultural Cognitive Examination (CCCE; range:3–96). We used descriptive analyses to estimate multimorbidity prevalence and identify disease patterns, then used weighted linear regression (adjusted for age, sex, martial/partnership status, education, literacy, and household income and wealth) to estimate associations between multimorbidity patterns and cognitive change (modeled as CCCE-2015 regressed on CCCE-2012). In 2012, 50.7% of respondents reported multimorbidity and average CCCE score was 46.6 (SD=17.2). From 2012–2015, CCCE decreased on average 2.7 units (SD=13.1). Disease patterns with ≥ 2% prevalence included hypertension+depression (6.0%), hypertension+arthritis (5.9%), hypertension+diabetes (5.8%), hypertension+arthritis+depression (5.4%), hypertension+diabetes+depression (2.8%), hypertension+diabetes+arthritis (2.7%), and arthritis+depression (2.1%). Compared to those reporting no conditions, respondents reporting arthritis+depression (b=-3.88, CI=-6.11:-1.66), hypertension+diabetes (b=-3.72, CI=-5.33:-2.11), or hypertension+diabetes+depression (b=-3.41, CI=-5.32:-1.21) experienced greater cognitive decline. Our results suggest diabetes and depression are common elements of multimorbidity associated with cognitive decline in Mexican older adults.

Changes in Cognitive Functions after Carotid Endarterectomy and Carotid Stenting: A Decade-Apart Comparison.

This study investigates changes in cognitive function in patients with severe carotid stenosis who underwent carotid endarterectomy (CEA) and carotid stenting (CAS) over two decades. We compared cognitive function within 30 days after the procedure in 267 patients (first 100 each for CEA and CAS in two periods: 2008-2012 and 2018-2022) in a single institution. Assessments used Adenbrooke's Cognitive Examination-Revised (ACE-R), the Mini-Mental State Examination (MMSE), Speech Fluency Test (SFT), and Clock Drawing Test (CDT), conducted before and 30 ± 2 days after surgery. Patients (mean age 67.2 years, 70%+ carotid stenosis) exhibited different cognitive changes over periods. In 2008-2012, significant declines in MMSE (CEA, p = 0.049) and CDT (CAS, p = 0.015) were observed among asymptomatic patients. On the contrary, in 2018-2022, improvements were observed in ACE-R and MMSE for symptomatic and asymptomatic patients undergoing CEA and CAS. Over a decade, advances in interventional techniques and patient management have reduced risks of cognitive decline in patients with asymptomatic carotid stenosis and also have improved cognitive functions in both symptomatic and asymptomatic individuals.

Shorter Reperfusion Time in Stroke is Associated with Better Cognition.

Cognitive changes that result from cerebrovascular disease contribute to a poor functional outcome with reduced quality of life. Among patients undergoing endovascular therapy (EVT), we aim to assess cognitive function and evaluate the impact of reperfusion time in cognitive performance. Patients with acute right anterior circulation strokes that underwent EVT between January 2018 and August 2020 at Centro Hospitalar de Vila Nova de Gaia/Espinho, participated in the study. Modified treatment in cerebral infarction (mTICI) assessed the level of recanalization. Cognitive evaluation was assessed with Addenbrooke's Cognitive Examination revised (ACE-R). Multiple linear regression analyses were used to determine the association between time for recanalization and ACE-R. The level of significance adopted was 0.05. The mean age of participants was 71.5 (interquartile range [IQR] 62.0-78.2) years, and 50% (22) were women. The median time after stroke was 28.6 months (IQR 18.94-31.55). All patients in our sample had a successful level of recanalization with EVT (mTICI ≥ 2b). Time for recanalization showed an inverse association with the ACE-R (b = -0.0207, P = 0.0203). Also the mRS at 3 months had an inverse association with cognition (b = -5.2803, p = 0.0095). Level of education had a strong and direct relationship with ACE-R results (b = 3.0869, p < 0.0001). Longer time between stroke symptoms and recanalization with EVT in patients with right hemisphere ischemic stroke lead to lower ACE-R scores. Measures to improve door-to-recanalization time are also important for cognitive performance after ischemic stroke.

Relationship between occupation and cognitive performance in patients with cognitive impairment. Preliminary study

AbstractBackgroundPrevious studies showed the protective effect of cognitive reserve for the development of cognitive impairment and dementia symptoms. Some factors have been postulated that may influence cognitive reserve, including education, participation in cognitively stimulating activities, and occupation. It has been observed that certain occupations have better cognitive performance and different professions may generate better functioning in certain cognitive domains than others. The aim of this study is to assess whether there is greater strength in certain cognitive domains related to the occupations of patients with subjective memory complaints or mild cognitive impairment diagnosis.MethodRetrospective observational study with patients under follow‐up in a memory clinic in Buenos Aires, Argentina. Patients with &gt;17 education years, &gt; 50 years with a diagnosis of subjective memory complaint and/or mild cognitive impairment of any origin were included. Subjects with dementia were excluded. The occupations were classified according to the ISCO‐88 (2008 International Labor Organization) utilizing professionals’ subcategory. A complete cognitive evaluation was performed in all the patients, including memory, attention, language, executive functions, and visuospatial domains. For the statistical analysis, the z scores of the results of the different cognitive tests were used and parametric student`s‐t tests were performed using the Graphpad software,ResultA total of 57 patients from our center were included to date. The mean age was 71 (55‐85), years of education 19 (17‐25) and a total of 35 (61%) women. The mean of Addenbrooke’s Cognitive Examination (ACE) was 91.3 (82‐99). The predominant occupation was in the health category with a total of 24 (42%) patients. No statistically significant differences were obtained in the values of the different cognitive tests of each occupational category and the value of the total population.ConclusionThe study has not shown significant differences between specific cognitive variables and occupation in patients with cognitive impairment. However, a larger number of subjects would be needed to support this statement. It is important to note that extra‐work activities of patients that can also influence their cognitive performance have not been taken into account.

Perspectives of General Practitioners on signaling and diagnosing dementia

AbstractBackgroundAlthough a timely diagnosis of dementia is beneficial for patients, their relatives, and society, people with dementia often remain undiagnosed or receive a diagnosis at a relatively late stage (Lang 2017). General practitioners (GPs) have a prominent role in the detection of dementia, yet GPs experience several barriers in diagnosing dementia in primary care (Koch 2010). This study aims to explore the experiences and perspectives of GPs in diagnosing dementia in primary care.MethodA qualitative study was conducted consisting of semi‐structured interviews with 10 Dutch GPs purposively selected using maximum variation sampling. The study was an initiative of Alzheimer Center Groningen as part of ABOARD (A Personalized Medicine Approach for Alzheimer’s Disease). Overall topics included: experiences in signaling dementia; thoughts about the decision to wait in diagnosing dementia, to perform diagnostics, or to refer to a medical specialist for diagnosing dementia; and the needs of GPs in the diagnostic process of dementia. Interview transcripts were analyzed in multiple rounds by a multidisciplinary research team using thematic analysis with a phenomenological approach.ResultOverarching themes were ‘initiation of the diagnostic trajectory’, ‘timing of diagnosis’, ‘relevance of a formal diagnosis’, ‘division of roles and responsibilities, ‘patient denial’, ‘patient‐physician relationship’, ‘crisis’, and ‘arranging care after diagnosis’. Key findings within the ‘initiation of the diagnostic trajectory’ theme were that observations from people around patients (family, community nurse, practice nurse, pharmacist, or medical specialist) were often signals for GPs to start a conversation about dementia and diagnostic possibilities. The diagnostic trajectory rarely started with a request for help from the patient. Patient denial was described as a major obstacle in diagnosing dementia and arranging appropriate care subsequently. A proactive practice policy to detect and monitor cognitive impairment was a key facilitator to achieve a timely diagnosis and prevent crises in dementia. For example, GPs favored regular home visits by a practice nurse and low‐threshold cognitive examination; a long‐term physician‐patient relationship; and successful interdisciplinary collaboration with local care providers, especially consultation of an elderly care physician.ConclusionPatient denial and surrounding people are important barriers and facilitators, respectively, to the diagnostic process of dementia.

Using Natural Language Processing to identify psychiatric symptoms related to Alzheimer’s disease: a novel tool to enhance molecular brain research in Alzheimer’s disease

AbstractBackgroundNeuropsychiatric symptoms (NPS), such as anxiety, depression, or agitation, are common across different stages of Alzheimer’s disease (AD). However, their molecular course is still poorly understood. While post‐mortem brain research provides a unique source to study brain‐specific molecular changes, clinical characterization of post‐mortem brain donors is challenging and primarily subject to case‐control designs. Here, we present a novel approach to post‐mortem brain donor characterization using natural language processing (NLP).MethodWe analyzed electronic health records (HER) of 92 brain donors (46 males, 46 females, mean age 81.9 years, B&amp;B 0 ‐ VI) using NLP‐based NIMH Research Domain Criteria (RDoC) quantification. Individual RDoC scores were regressed to their neuropathological findings or RNAseq data from two independent brain regions, BA32 and insula.ResultNeuritic plaques (NP) in all four cortices show a high association with RDoC “cognition”, controlled for age and sex (frontal: ß = 0.38, p &lt; 0.001; parietal: ß = 0.35, p &lt; 0.001; temporal: ß = 0.37, p &lt; 0.001; occipital: ß = 0.37, p &lt; 0.001). These findings align with prior clinicopathological correlation studies where cognitive examinations were performed within one year before death (Nelson et al., J Neuropathol Exp Neurol, 2012). At pFDR&lt;0.05, we identified 492 differentially expressed genes (DEGs) in the insula and 333 DEGs in the BA32. We have further built a model regressing individual RDoC levels against their DEGs in the two brain regions. In each domain, we observed a cluster of genes that is up‐ or downregulated in relation to their RDoC score (higher/lower domain burden). In addition, we saw that the majority of DEGs are RDoC‐specific. 223 DEGs were uniquely related to one domain (170 DEGs in the insula and 53 DEGs in BA32), while a total of 211 DEGs were associated with at least two domains (151 DEGs in the insula and 60 DEGs in BA32).ConclusionNLP‐based analysis of RDoC can be applied to post‐mortem case collections to phenotype brain donors and show promising associations with neuropathology or RNAseq data that can be used to discover novel molecular pathways related to psychiatric symptoms.

Electrophysiological correlates of objective memory impairments in community‐dwelling older adults at risk of dementia

AbstractBackgroundThe electrophysiological correlates of Short‐Term Memory Binding (STMB) have been previously investigated in older adults at risk of dementia (i.e., Mild Cognitive Impairment ‐MCI). Pietto et al. (2016) reported reduced early electrophysiological activity (100‐250 ms) over fronto‐central (FC) and parieto‐occipital (PO) regions in MCI patients recruited from clinic. We investigated if such an electrophysiological pattern is also observed in a larger sample of community‐dwelling older adults with MCI who had not sought medical advice.MethodsA sample of 215 community‐dwelling older adults were recruited into the study. They were assessed with a battery of cognitive tests including CERAD (Aguirre‐Acevedo et al., 2016), the Addenbrooke’s Cognitive Examination (ACE‐R), the STMB Task, clinical, and functional scales. The STMB task assesses the ability to detect changes between two consecutive visual arrays of coloured shapes. Changes consisted of shapes swapping colours (the binding condition). Time‐locked EEG signals were collected while participants performed the STMB task. Monte Carlo tests and non‐parametric bootstrapping running 1000 permutations revealed electrodes and time windows of relevance.ResultsA group of 108 participants met classical criteria for MCI (Petersen, 2004; Winblad et al., 2004). They showed impaired STMB abilities. ERP analyses revealed significant Group x Time Windows interactions (p&lt;0.01). Early ERP showed reduced neural recruitment (MCI&lt;HC) on the left PO and right centro‐parietal (CP) (300‐500ms) regions during shape‐colour encoding, and on PO bilaterally and left FC during retrieval (150‐450ms). Late ERP showed increased neural recruitment (MCI&gt;HC) on right fronto‐central (FC) regions (900‐1200ms) during shape‐colour encoding, and on left FC and PO regions (872‐1200ms) during retrieval.ConclusionAltered spatio‐temporal dynamics underpinning STMB deficits in MCI patients followed a pattern similar to that described by Pietto et al. (2016). Of note, we observed hyper‐recruitment for late ERP linked to encoding and retrieval over anterior and posterior regions of the STMB network. Such hyper‐recruitment may reflect compensatory changes in the early stages of MCI. These results confirm the usefulness of EEG‐based cognitive biomarkers to screen community‐dwelling older adults at risk of dementia.Aguirre‐Acevedo et al. (2016). Int. Psychogeriatr, 28(3), 503‐510.Pietto et al. (2016). Journal of Alzheimer’s Disease, 53(4), 1325‐1340.

Exploring the association between VLOM ratio and years of education in MCI and normal aging urban cohort

AbstractBackgroundMild Cognitive Impairment (MCI) is a transition state of cognitive decline from healthy brain to dementia. It is a prodrome of Alzheimer’s disease. Verbal‐Language/Orientation‐Memory (VLOM) ratio, a simply calculated index compares its language and memory scores helps to differentiate between Alzheimer’s disease and frontotemporal dementia (Mathuranath, et al.,2000). VLOM ratio is helpful in prognosticating and planning future management of the disease. The previous studies have shown the association of scores in cognitive domains with years of education (Nieto A, et al.,2016). Therefore, the objective of the study is to explore the association of years of education with VLOM ratio in MCI participants and normal participants.MethodCross sectional analysis was done using the baseline data from the cohort study Tata Longitudinal Study of Ageing (TLSA) from urban Bengaluru, India. Clinical dementia rating scale (CDR) was used to classify participants into normal and MCI category. CDR score of 0 was considered as normal, score of 0.5 as MCI. ACE III‐R (Addenbrooke’s Cognitive Examination III‐R) a neuropsychological test was administered and verbal fluency plus language to orientation plus memory (VLOM) ratio was calculated. Further, years of education was classified into three levels and comparison of VLOM ratio was made within these levels of education groups in both MCI and normal participants. Mann Whitney U test was used to compare the VLOM ratio between MCI and normal participants. VLOM ratio and years of education among the MCI and normal participants was compared using Kruskal‐Wallis test.ResultsAmong 953 participants, 69 had MCI and 884 participants had normal cognition. Comparison of VLOM ratio between MCI and normal participants showed a significant difference, with higher VLOM ratio in MCI participants (Median (IQR)) = 0.97 (0.11) vs 0.95 (0.09); p = 0.01). There was no significant difference in VLOM ratio between years of education in both normal and MCI participants.ConclusionThe VLOM ratio found to be higher in MCI group indicating that the scores in orientation and memory domain might be lower in MCI compared to Normal participants. There was no association of VLOM ratio with years of education in normal and MCI participants.

Evaluation of Cognitive Function in Patients with Type 2 Diabetes Mellitus: Comparison with Age-Matched Controls: A Prospective Study

Abstract Introduction: A relative deficiency in insulin production, chronic hyperglycemia, abnormalities in carbohydrate and lipid metabolism, and insulin resistance are all the symptoms of type 2 diabetes mellitus (T2DM). The brain is one of many organ systems that is negatively impacted, increasing the likelihood of cognitive decline. Aim: Evaluation of cognitive functions in patients with T2DM and comparison with aged-matched controls. Methodology: Fifty T2DM patients as well as 50 age-matched controls were subjected to Adden Brooke’s Cognitive Examination (ACE-III). The examination assesses attention, orientation, memory, language, fluency, visual perception, and visuospatial skills. It comprises tests of memory (7-item analysis), letter fluency, clock drawing, and memory recall. The optimal ACE-III cutoff scores to detect mild cognitive impairment and dementia are 88/89 (sensitivity 0.77 and specificity 0.92) and 75/76 (sensitivity 0.82 and specificity 0.90), respectively. The comparison of scores of patients and controls was done using the appropriate statistical tests (SPSS version 25). Statistical Analysis Used: Unpaired t-test, Chi-square test, and Pearson correlation coefficient test. Results: The mean ± standard deviation ACE-III scores of T2DM patients and controls were 81.48 ± 12.426 and 86.2 ± 10.447, respectively; the difference between them was not statistically significant. There was a decrease in attention, memory, fluency, and visuospatial ability in cases as compared to controls, but the difference was not statistically significant. Dementia was observed in 30% of cases and 20% of controls. Mild cognitive impairment was similar in both groups. Weak association was seen between the number of drugs prescribed and duration of disease with ACE-III scores. Conclusion: We find a negative association of cognitive function and T2DM.

Participating in leisure time physical activity across adulthood and later‐life brain health: 30 years follow‐up in 1946 British Birth Cohort

AbstractBackgroundWe assess if, and at which ages during 30 years of adulthood, undertaking leisure time physical activity (LTPA) is associated with brain health at age 70, and to what extent brain health metrics explain the positive association between LTPA and later‐life cognition.MethodParticipants from the British 1946 birth cohort prospectively reported LTPA five times between ages 36 and 69. Metrics were categorised into: not active (no participation/month); active (participated once or more/month); and summed. Participants underwent 18F‐florbetapir Aβ‐PET and MRI at age 70 (n = 468, 49% female). Regression analyses examined associations between LTPA metrics and later‐life brain health including Aβ‐PET, TIV‐adjusted brain, hippocampal and log‐transformed‐white matter hyperintensity (WMH) volume, adjusting for sex, scan age, childhood cognition, education, and childhood socioeconomic position. Effect modification by sex and APOE‐ε4 were examined. The relationship between cumulative LPTA and later‐life cognition (Addenbrooke’s cognitive Examination (ACE‐III)) was assessed adjusting for brain health measures.ResultParticipation in LTPA was associated with better brain health at age 70. For brain volume and WMH volume, the strongest associations were with LTPA at age 69 (Figure 1). Being active in one or more period across adulthood was linked to larger hippocampal volume (Figure 1); this relationship was modified by APOE‐ε4 (p&lt;0.01), with a stronger effect shown in ε4 carriers (Figure 2). LTPA at age 43 was also associated with larger hippocampal volumes. There was no evidence of associations with amyloid status. The positive association between cumulative LTPA and better cognition was not attenuated by any of the brain health measures (Figure 3).ConclusionWe provide evidence that LTPA across adulthood is linked to brain health at age 70; being active throughout adulthood was associated with larger hippocampal volume, particularly in APOE ε4 carriers; and being active in later‐life was linked to less WMH and larger brain volume at age 70. However, these brain health metrics did not explain the relationship between LPTA and better cognitive scores, suggesting that these pathways may not underlie the inferred cognitive benefit at this age. Our findings warrant further research to shed light on the mechanisms of physical activity as a potential disease‐modifying intervention of brain health.

Pesticides and cognitive impairment in older adults: evidence from southern Colombia

AbstractBackgroundEnvironmental exposure to specific chemical groups of pesticides (Carbamates, Organophosphates, Pyrethroids, and Organochlorines), as well as the non or inadequate use of personal protective equipment during pest management, have been associated to cognitive decline and increased risk of dementia (Hayden et al., 2010). This study investigated cognitive functioning in older adults exposed to pesticides in southern Colombia.MethodsA sample of 353 older adults was recruited. Of these, 279 had not been exposed to pesticides (n‐Exp) and 74 had (Exp). They were matched according to age [n‐Ex: 63.80 (3.25), Ex: 63.30 (6.96), t = 0.618, p = 0.538] and years of education [n‐Ex: 9.29 (6.28), Ex: 8.95(6.35), t = 0.418, p = 0.676]. They were assessed with a battery of cognitive tests including CERAD (Aguirre‐Acevedo et al., 2016), The Addenbrooke’s Cognitive Examination (ACE‐R), the Free and Cued Selective Reminding Test (FCSRT) and questionnaires.ResultsFDR corrected comparisons revealed overall lower cognitive abilities in the Exp group (ACE‐R, q = 0.027). They also displayed Memory (FCSRT, q = 0.020; World List Learning q = 0.014) and Constructional Praxis (q = 0.007) impairments. Of those exposed, 73% reported no use of personal protective equipment, and neither the participants nor their family members reported concerns about cognitive decline [Self‐reported: n‐Exp: 14.27 (7.44), Exp: 14.92 (7.98), t = ‐0.654, p = 0.513; Family‐reported: n‐Exp: 10.43 (7.12), Exp: 10.26 (7.45), t = ‐0.182, p = 0.856].ConclusionOlder adults from southern Colombia who have been exposed to pesticides show significant cognitive impairments, which have gone unnoticed by both the affected individuals and their family. Cognitive abilities found to be affected have been associated with risk of dementia caused by Alzheimer’s Disease or Parkinson’s Disease (FCSRT and Constructional Praxis). These types of dementia have been previously associated with this environmental risk factor (Chin‐Chan et al., 2015). More awareness about environmental factors and actions to mitigate their risk are urgently needed, and should be considered by future recommendations (e.g., Livingston et al., 2020).Aguirre‐Acevedo et al. (2016). Int. Psychogeriatr, 28(3), 503‐510. https://doi.org/S1041610215001660.Chin‐Chan et al. (2015). Frontiers in Cellular Neuroscience, 9. https://www.frontiersin.org/articles/10.3389/fncel.2015.00124Hayden et al. (2010). Neurology, 74(19), 1524‐1530. https://doi.org/10.1212/WNL.0b013e3181dd4423Livingston et al. (2020). Lancet, 396(10248), 413‐446. https://doi.org/10.1016/S0140‐6736(20)30367‐6

Plasma glucose does not influence performance on standard cognitive screening tests in a mixed memory clinic cohort

AbstractBackgroundIt has been shown under experimental conditions that cognitive performance, especially working memory, is impaired in type I and type II diabetes during hyperglycemic and hypoglycemic conditions, perhaps due to altered cerebral glucose metabolism. It is not known if patients with neurodegenerative diseases, who also exhibit pathological cerebral glucose metabolism, are affected in a similar manner by their intrinsic plasma glucose levels. We aimed to test if performance on two standard cognitive screening tests is influenced by intrinsic plasma glucose levels in a memory clinic cohort.MethodIn this retrospective study, we included patients from the Copenhagen Memory Clinic Cohort (CMCC) with an available Mini Mental‐State Examination (MMSE) test score and a plasma glucose measurement performed in conjunction with cognitive testing. Patients were included from the inception of the cohort in 2008 till September 2021. We built linear regression models with MMSE and Addenbrooke’s Cognitive Examination (ACE) test scores as the outcome and plasma glucose as the explaining variable and adjusted models for age, sex and diabetes (plasma glucose measurement &gt; 11.1 mmol/L). We explored non‐linear relationships by adding squared terms to the models and by fitting cubic spline regression models.ResultIn total, 2714 patients had an available MMSE score and a plasma glucose measurement. Patients had a mean age of 71.6 years [range 19‐99] and a baseline plasma glucose level of 5.8 mmol/L [range 2.7‐28.1]. A total of 581 of patients had a plasma glucose level outside normal range (&lt;4.2 or &gt;6.3 mmol/L). A total of 31.2% of the cohort studied had a diagnosis of Alzheimer’s disease (AD). MMSE and ACE total scores were not influenced by plasma glucose in a linear nor in a non‐linear fashion, when we adjusted for age, sex and diabetes. Sub‐group analyses in patients with AD and in patients with cerebrovascular disease showed similar results.ConclusionPlasma glucose levels inside normal range were not shown to influence performance on routinely applied cognitive tests and do not need be taken into consideration when interpreting test results from memory clinic patients.

Clinical Manifestations.

The capacity to handle money and personal finances is crucial for living independently. Cognitive decline can lead to financial mismanagement (e.g., forgetting to pay bills, overspending) and exploitation (e.g., falling for financial scams). While greater susceptibility to financial mismanagement and exploitation is commonly reported by carers of people with dementia, objective neuropsychological measures of these financial skills are scarce. It is also unclear whether profiles of change in financial skills vary across different stages and subtypes of dementia. A normative sample of 112 healthy controls and individuals with mild cognitive impairment (MCI; n = 16), Alzheimer's disease (AD; n = 7) or behavioural-variant frontotemporal dementia (bvFTD; n = 18) completed a novel neuropsychological Test of Financial Skills (TOFS), which assessed performance across three key areas: everyday financial tasks, susceptibility to financial scams and financial goal planning. For all patients and controls, measures of dementia severity (Clinical Dementia Rating Scale) and general cognition (Addenbrooke's Cognitive Examination, 3rd Ed.) were also collected. Relative to controls, AD and bvFTD patients showed lower overall performance on the TOFS, whereas MCI patients did not differ significantly from controls. While AD and bvFTD patients showed similar levels of impairment on everyday financial tasks and financial goal planning, bvFTD patients performed significantly worse on the financial scams subtest. Across all participants, lower TOFS performance was associated with greater dementia severity and cognitive impairment. Our results are consistent with previous studies of carer-reported changes in financial mismanagement and exploitation in people with dementia. Notably, we found important differences in the areas of financial skills impacted by different stages and subtypes of dementia. These findings provide novel insights into the different factors that contribute to deficits in financial skills in people with dementia, highlight the importance of objective neuropsychological assessments in this area, and open avenues for targeted financial support strategies.

Dementia diagnosis using Addenbrooke’s Cognitive Examination in low literates and illiterates in three Indian languages

AbstractBackgroundWith a rising burden of dementia globally, there is a need to harmonize dementia diagnosis and research across diverse populations. Majority of dementia patients reside in low‐middle income countries (LMICs) such as India. Major challenges in the diagnosis of dementia in LMICs include the lack of a proper diagnostic tool for low literates and illiterates besides the lack of awareness of society about the disease. Addenbrooke’s Cognitive Examination‐III (ACE‐III) is a screening instrument with good validity and reliability to diagnose patients with mild cognitive impairment (MCI) and dementia. Although ACE‐III has been adapted to many languages both in India and worldwide, it has not been adapted for the low literate and illiterate population. The objective of the study is to i) develop a culturally relevant illiterate ACE‐III for the Indian context and standardize the instrument across three commonly used Indian languages: Hindi, Bengali, and Kannada; and ii) to establish the sensitivity and specificity of the illiterate Indian versions of ACE‐III to detect dementia and MCI.MethodThe illiterate version of ACE‐III was adapted from the literate version of ACE‐III based on the suggestions from multidisciplinary expert panel comprising cognitive neurologists, stroke specialists, speech–language pathologists and psychologists from different centres (see Figure 1). In total, 84 controls, 50 dementia, and 46 MCI patients were recruited across three cities in India for the validation study. Psychometric properties of adapted versions were examined, and their sensitivity and specificity were established.ResultThe sensitivity and specificity of illiterate ACE‐III in identifying dementia ranged from 93.3% to 99.9%, sensitivity for MCI ranged from 93.3% to 99%, and specificity from 72.7% to 99.9%. Optimum cut‐off scores were established (see Table 1).ConclusionThe adapted versions of illiterate ACE‐III have been standardized and validated for use across three Indian languages, with high diagnostic accuracy in identifying dementia and MCI in a linguistically diverse context. The study provides a cognitive screening tool that can be used to uniformly diagnose cognitive impairment in people speaking different languages from both rural and urban populations located across India.

1. Validity and reliability of CAMCOG‐DS2 and other cognitive outcomes measures for clinical trials of AD in DS

AbstractBackgroundDown syndrome (DS) is an important population to include in clinical trials aiming to prevent or delay Alzheimer’s disease (AD). This talk will summarise previous work in trajectory modelling to identify the earliest ages of change in cognition and the optimal sample sizes needed for clinical trials in DS. It will present validate data on the new version of the Cambridge Cognitive Examination–Down syndrome version II (CAMCOG‐DS‐II) alongside established cognitive tests. The CAMCOG‐DS‐II has been developed to assess cognitive impairments associated with dementia in people with DS.MethodThis was an observational, multicentre, longitudinal study (n = 174) across seven existing cohorts in six different European languages to validate cognitive tests in adults with DS aged 25 years and older. It assessed the relationships between tests of cognition, behaviour, function, and health. Cognitive assessments included the CAMCOG‐DS‐II, the CANTAB Paired Associates Learning (PAL) Task, the modified Cued Recall Test (mCRT) and the Purdue Pegboard Test. We examined correlations between tests, group differences between those with and without dementia and explored test‐retest reliability of the CAMCOG‐DS‐II.ResultOur results showed that completion rates for the CAMCOG‐DS‐II were high, and floor and ceiling effects were low. The CAMCOG‐DS‐II memory sub‐score correlated significantly with the mCRT total recall score (Spearman’s ∼0.5), and the praxis sub‐score significantly correlated with the Purdue Pegboard total score (Spearman’s &gt;0.7).ConclusionThere is currently a critical lack of suitable diagnostic and outcome measures that can be used in clinical trials. These results show that the CAMCOG‐DS‐II is a feasible test of cognition and will help to provide sensitive cognitive endpoints for clinical trials which are seeking to find suitable treatments for AD in adults with DS. Future analysis will include trajectories of change from baseline to one year of follow up for each primary outcome measure.