The 2022 symposium on dementia and brain aging in low- and middle-income countries: Highlights on research, diagnosis, care, and impact.

Two of every three persons living with dementia reside in low- and middle-income countries (LMICs). The projected increase in global dementia rates is expected to affect LMICs disproportionately. However, the majority of global dementia care costs occur in high-income countries (HICs), with dementia research predominantly focusing on HICs. This imbalance necessitates LMIC-focused research to ensure that characterization of dementia accurately reflects the involvement and specificities of diverse populations. Development of effective preventive, diagnostic, and therapeutic approaches for dementia in LMICs requires targeted, personalized, and harmonized efforts. Our article represents timely discussions at the 2022 Symposium on Dementia and Brain Aging in LMICs that identified the foremost opportunities to advance dementia research, differential diagnosis, use of neuropsychometric tools, awareness, and treatment options. We highlight key topics discussed at the meeting and provide future recommendations to foster a more equitable landscape for dementia prevention, diagnosis, care, policy, and management in LMICs. HIGHLIGHTS: Two-thirds of persons with dementia live in LMICs, yet research and costs are skewed toward HICs. LMICs expect dementia prevalence to more than double, accompanied by socioeconomic disparities. The 2022 Symposium on Dementia in LMICs addressed advances in research, diagnosis, prevention, and policy. The Nairobi Declaration urges global action to enhance dementia outcomes in LMICs.

Gaps in clinical research in frontotemporal dementia: A call for diversity and disparities-focused research.

Frontotemporal dementia (FTD) is one of the leading causes of dementia before age 65 and often manifests as abnormal behavior (in behavioral variant FTD) or language impairment (in primary progressive aphasia). FTD's exact clinical presentation varies by culture, language, education, social norms, and other socioeconomic factors; current research and clinical practice, however, is mainly based on studies conducted in North America and Western Europe. Changes in diagnostic criteria and procedures as well as new or adapted cognitive tests are likely needed to take into consideration global diversity. This perspective paper by two professional interest areas of the Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment examines how increasing global diversity impacts the clinical presentation, screening, assessment, and diagnosis of FTD and its treatment and care. It subsequently provides recommendations to address immediate needs to advance global FTD research and clinical practice.

Delay in the diagnosis of dementia in urban India: Role of dementia subtype and age at onset.

BACKGROUND: Early diagnosis of dementia is crucial for timely intervention. However, frequently, there is a substantial delay in diagnosis. Therefore, it is essential to recognise and address the barriers to early diagnosis. These have not been systematically studied in India. We at a specialist memory clinic in India investigated the time from symptom onset to diagnosis of dementia and factors contributing to the delay. METHODS: In this cross-sectional study, consecutive patients with dementia (n = 855) seen at a private hospital underwent a standard clinical assessment and investigations. The primary outcome variable was time from symptom onset to diagnosis (TTD). The association of age, education, gender, dementia subtype, and age of onset on TTD were examined using a univariate analysis of covariance. RESULTS: The median TTD was 24 months; 43% were diagnosed after 24 months. There was a significant association between TTD and age at onset (young onset-median 36 months vs. late onset-24 months) and dementia subtype. Patients with vascular dementia were diagnosed significantly earlier as compared to patients with Alzheimer's disease (AD) and frontotemporal dementia (FTD) [median 18, 24, and 30 months, respectively]. There was no effect of gender or education on the TTD. CONCLUSION: About 40% of patients with dementia were diagnosed more than 2 years after symptom onset, particularly young onset dementias and FTD. Our study findings highlight the gaps in diagnosing patients with dementia in urban India and have significant implications for developing and implementing multifaceted interventions to improve the early diagnosis of dementia.

Recommendations to distinguish behavioural variant frontotemporal dementia from psychiatric disorders.

The behavioural variant of frontotemporal dementia (bvFTD) is a frequent cause of early-onset dementia. The diagnosis of bvFTD remains challenging because of the limited accuracy of neuroimaging in the early disease stages and the absence of molecular biomarkers, and therefore relies predominantly on clinical assessment. BvFTD shows significant symptomatic overlap with non-degenerative primary psychiatric disorders including major depressive disorder, bipolar disorder, schizophrenia, obsessive-compulsive disorder, autism spectrum disorders and even personality disorders. To date, ∼50% of patients with bvFTD receive a prior psychiatric diagnosis, and average diagnostic delay is up to 5-6 years from symptom onset. It is also not uncommon for patients with primary psychiatric disorders to be wrongly diagnosed with bvFTD. The Neuropsychiatric International Consortium for Frontotemporal Dementia was recently established to determine the current best clinical practice and set up an international collaboration to share a common dataset for future research. The goal of the present paper was to review the existing literature on the diagnosis of bvFTD and its differential diagnosis with primary psychiatric disorders to provide consensus recommendations on the clinical assessment. A systematic literature search with a narrative review was performed to determine all bvFTD-related diagnostic evidence for the following topics: bvFTD history taking, psychiatric assessment, clinical scales, physical and neurological examination, bedside cognitive tests, neuropsychological assessment, social cognition, structural neuroimaging, functional neuroimaging, CSF and genetic testing. For each topic, responsible team members proposed a set of minimal requirements, optimal clinical recommendations, and tools requiring further research or those that should be developed. Recommendations were listed if they reached a ≥ 85% expert consensus based on an online survey among all consortium participants. New recommendations include performing at least one formal social cognition test in the standard neuropsychological battery for bvFTD. We emphasize the importance of 3D-T1 brain MRI with a standardized review protocol including validated visual atrophy rating scales, and to consider volumetric analyses if available. We clarify the role of 18F-fluorodeoxyglucose PET for the exclusion of bvFTD when normal, whereas non-specific regional metabolism abnormalities should not be over-interpreted in the case of a psychiatric differential diagnosis. We highlight the potential role of serum or CSF neurofilament light chain to differentiate bvFTD from primary psychiatric disorders. Finally, based on the increasing literature and clinical experience, the consortium determined that screening for C9orf72 mutation should be performed in all possible/probable bvFTD cases or suspected cases with strong psychiatric features.

Frontotemporal Dementia: A Cross-Cultural Perspective.

It is predictable that syndromes of frontotemporal dementia (FTD) may have a worldwide distribution; however, data available on their incidence and prevalence are variable. This variability most likely reflects disparities across regions in the distribution of the expertise, technology, and resources available for FTD research and care. Important discoveries have been made regarding FTD's phenotypes, genetics, and cultural influences on the expression of symptoms; however, in many countries, there are barriers posed by a dearth of resources. There are pressing needs to further develop research on FTD: including first, population studies designed to fill the gaps in our knowledge about FTD's frequency and risk factors in developing regions and among minority groups in developed countries. It is also necessary to facilitate the psychometric characterization of contemporary diagnostic criteria and their translation to different languages and cultural contexts. Furthermore, much needed is the analysis of differences in the genetic risk factors for FTD, particularly non-Mendelian susceptibility factors. It is hoped that reflections on FTD from an international perspective will spur an extension of the vibrant multicenter collaborations, that exist in North America and Europe, toward new centers to be established and supported in the developing regions of the world.

Standardising Dementia Diagnosis Across Linguistic and Educational Diversity: Study Design of the Indian Council of Medical Research-Neurocognitive Tool Box (ICMR-NCTB).

OBJECTIVES: While the burden of dementia is increasing in low- and middle-income countries, there is a low rate of diagnosis and paucity of research in these regions. A major challenge to study dementia is the limited availability of standardised diagnostic tools for use in populations with linguistic and educational diversity. The objectives of the study were to develop a standardised and comprehensive neurocognitive test battery to diagnose dementia and mild cognitive impairment (MCI) due to varied etiologies, across different languages and educational levels in India, to facilitate research efforts in diverse settings. METHODS: A multidisciplinary expert group formed by Indian Council of Medical Research (ICMR) collaborated towards adapting and validating a neurocognitive test battery, that is, the ICMR Neurocognitive Tool Box (ICMR-NCTB) in five Indian languages (Hindi, Bengali, Telugu, Kannada, and Malayalam), for illiterates and literates, to standardise diagnosis of dementia and MCI in India. RESULTS: Following a review of existing international and national efforts at standardising dementia diagnosis, the ICMR-NCTB was developed and adapted to the Indian setting of sociolinguistic diversity. The battery consisted of tests of cognition, behaviour, and functional activities. A uniform protocol for diagnosis of normal cognition, MCI, and dementia due to neurodegenerative diseases and stroke was followed in six centres. A systematic plan for validating the ICMR-NCTB and establishing cut-off values in a diverse multicentric cohort was developed. CONCLUSIONS: A key outcome was the development of a comprehensive diagnostic tool for diagnosis of dementia and MCI due to varied etiologies, in the diverse socio-demographic setting of India.

Efficacy of Trunk Regimes on Balance, Mobility, Physical Function, and Community Reintegration in Chronic Stroke: A Parallel-Group Randomized Trial.

OBJECTIVE: The study objective was to examine the efficacy of plinth and Swiss ball-based trunk exercise regimes on balance, mobility, physical function, and community reintegration compared with standard physiotherapy in chronic stroke. SUBJECTS AND METHODS: This observer-blinded parallel-group randomized trial was conducted in outpatient stroke units. People with chronic stroke aged between 30 and 75 years, first onset of unilateral cortical lesion, poor trunk performance, 10 m independent walking ability with or without walking aids, and absence of pusher syndrome were included. Trunk Impairment Scale 2.0, Brunel Balance Assessment, Tinetti scale, gait speed, Stroke Impact Scale-16, and Reintegration to Normal Living Index were the measures. Experimental interventions involved the practice of selective upper and lower trunk movements using either plinth or Swiss ball. Control group received standard physiotherapy. All the patients practiced 1 hour exercise session, 3 sessions a week over a duration of 6 weeks and followed up after 3 and 12 months. RESULTS: Of 108 patients allocated into 3 groups, baseline characteristics were similar. Postintervention compared with control group, the plinth, and Swiss ball groups showed significant mean changes in the outcome measures: trunk impairment scale 2.0 (3.6;4.1 points), Brunel Balance Assessment (1-level), Tinetti scale (5;5.2 points), gait speed (.06;.08 m/s), Stroke Impact Scale-16 (8.7;7.2 points), and community reintegration (7.6;8.8 points). These improvements were retained during 3-12 months' follow-up. Statistical significant was set at P < .05. CONCLUSION: Plinth and Swiss ball-based trunk exercise regimes showed significant improvements in balance, mobility, physical function, and community reintegration in chronic stroke as against standard physiotherapy.

Identifying Gaps and Barriers in Alzheimer's Disease and Related Dementia Research and Management in Low- and Middle-Income Countries: A Survey of Health Professionals and Researchers.

Background: The significant increase in Alzheimer's disease and related dementia prevalence is a global health crisis, acutely impacting low- and lower-middle and upper-middle-income countries (LLMICs/UMICs). Objective: The objective of this study is to identify key barriers and gaps in dementia care and research in LLMICs and UMICs. Methods: We conducted an international, cross-sectional survey among clinicians and healthcare professionals (n = 249 in 34 countries) across LLMICs and UMICs, exploring patient demographics, use of clinical diagnosis, dementia evaluation, screening/evaluation tools, and care and treatment. Results: Significant disparities were found in diagnostic practices, access to assessments, and access to care. On average, clinicians in LLMICs saw more patients, had less time for evaluations, lower use of formal screening and tools, and less access to biomarkers. They were also under-resourced compared to UMICs. Conclusions: The findings provide insights for policymakers, healthcare organizations, and researchers to address the complex challenges associated with dementia care in diverse settings. Addressing these challenges requires a multipronged approach involving local, national, and international stakeholders.

Core Stability Exercises Yield Multiple Benefits for Patients With Chronic Stroke: A Randomized Controlled Trial.

OBJECTIVE: This study examined the effect of core stability exercises on trunk control, core muscle strength, standing weight-bearing symmetry, and balance confidence of people with chronic stroke. DESIGN: This was an assessor-blinded randomized controlled trial involving 84 ambulatory patients with middle cerebral artery stroke, randomly assigned to three training groups. Two experimental groups practiced core stability exercises either on stable or on unstable support surfaces. In contrast, the control group received standard physiotherapy. All the participants underwent an hour-long training session a day, thrice a week over a 6-wk duration, and followed-up after 12 mos. Trunk Impairment Scale, core muscle strength, weight-bearing asymmetry in standing, and Activities-specific Balance Confidence scale were the outcome measures. RESULTS: Compared with the control group, the two experimental groups demonstrated a significant improvement on all the outcome measures from baseline to posttraining and from baseline to 12-mo follow-up (P < 0.001). The two experimental groups demonstrated no significant difference between them on all the measures (P > 0.05). CONCLUSIONS: Core stability exercises on stable and unstable support surfaces are equally beneficial in improving trunk control, core muscle strength, standing weight-bearing symmetry, and balance confidence of ambulatory patients with chronic stroke than the standard physiotherapy.

Bilingualism and Its Implications for Neuropsychological Evaluation.

OBJECTIVE: In the background of a large population of bilinguals globally, the study aimed to develop standards of neuropsychological testing in the context of bilingualism. Because bilingualism is known to affect cognitive processes, bilinguals and monolinguals were compared on their performance on cognitive tests, to investigate the possibility of the need for separate normative data for the two groups. METHOD: A comprehensive neuropsychological test battery, standardized across five Indian languages: the Indian Council of Medical Research-Neuro Cognitive Tool Box (ICMR-NCTB) was administered to 530 participants (267 monolingual and 263 bilinguals matched for age and education). A systematic method of testing cognition in bilinguals was developed; to identify the appropriate language for testing, ensure language proficiency of examiner, and to interpret the bilingual responses. Additionally, the performance of bilinguals on the ICMR-NCTB was compared with monolinguals. RESULTS: Cognitive testing in the bilingual context was performed in the most proficient language of the participants, by examiners well versed with the language. Results from the language-based tests suggested that the frequent occurrence of borrowed- and language-mixed words required consideration while scoring. The reported bilingual effect on cognitive processes did not reflect as differences in the performance between bilinguals and monolinguals. CONCLUSIONS: Observations from the study provide robust recommendations for neuropsychological testing in the context of bilingualism. Results indicate that separate normative data may not be required for bilinguals and monolinguals. The study will be relevant and provide a reference framework to address similar issues in the large population of bilinguals in other societies.

Striking loss of second language in bilingual patients with semantic dementia.

BACKGROUND: Studies of bilingual or multilingual patients with neurodegenerative diseases that disrupt language like the primary progressive aphasias (PPA) may contribute valuable information on language organization in the bilingual brain and on the factors affecting language decline. There is limited literature on bilingual PPA and in particular on semantic dementia, a type of PPA with selective loss of semantic memory. We studied the nature and severity of naming and comprehension deficits across languages in bilingual patients with semantic dementia (SD). METHODS: Sixteen bilingual patients with SD and 34 bilingual age-matched controls were administered the modified Boston Naming Test and components of Cambridge Semantic Battery. The patients' performance on picture naming and word comprehension was compared across languages and with controls. The most proficient language on self-rating was labelled as L1 and less proficient as L2. RESULTS: We observed striking loss of second language (L2) in SD for both receptive and expressive language, even in patients who were premorbidly fluent in their L2. Naming and comprehension in every patient's L2 were impaired relative to both their own first-language (L1) scores and controls' L2 scores. Furthermore, item-specific correct responses in each patient's L2 were a subset of their successes in L1. DISCUSSION: A striking contrast in performance between two languages in bilingual patients with SD indicates that a bilingual's L2 or less proficient language is more vulnerable to neurodegeneration. Our findings also support a common semantic network in the brain for the different languages of bilinguals.

Dementia Diagnosis in Seven Languages: The Addenbrooke's Cognitive Examination-III in India.

OBJECTIVE: With the rising burden of dementia globally, there is a need to harmonize dementia research across diverse populations. The Addenbrooke's Cognitive Examination-III (ACE-III) is a well-established cognitive screening tool to diagnose dementia. But there have been few efforts to standardize the use of ACE-III across cohorts speaking different languages. The present study aimed to standardize and validate ACE-III across seven Indian languages and to assess the diagnostic accuracy of the test to detect dementia and mild cognitive impairment (MCI) in the context of language heterogeneity. METHODS: The original ACE-III was adapted to Indian languages: Hindi, Telugu, Kannada, Malayalam, Urdu, Tamil, and Indian English by a multidisciplinary expert group. The ACE-III was standardized for use across all seven languages. In total, 757 controls, 242 dementia, and 204 MCI patients were recruited across five cities in India for the validation study. Psychometric properties of adapted versions were examined and their sensitivity and specificity were established. RESULTS: The sensitivity and specificity of ACE-III in identifying dementia ranged from 0.90 to 1, sensitivity for MCI ranged from 0.86 to 1, and specificity from 0.83 to 0.93. Education but not language was found to have an independent effect on ACE-III scores. Optimum cut-off scores were established separately for low education (≤10 years of education) and high education (>10 years of education) groups. CONCLUSIONS: The adapted versions of ACE-III have been standardized and validated for use across seven Indian languages, with high diagnostic accuracy in identifying dementia and MCI in a linguistically diverse context.

Residential care/assisted living staff may detect undiagnosed dementia using the minimum data set cognition scale.

OBJECTIVES: To estimate the sensitivity, specificity, and reliability of the Minimum Data Set Cognition Scale (MDS-COGS) in screening for undetected dementia when completed by direct care staff in residential care/assisted living (RC/AL) facilities and secondarily to determine the prevalence of dementia in the sample. DESIGN: A cross-sectional study in which staff were trained to complete the MDS-COGS. Research interviewers and a neuropsychologist obtained information on each participant. Two neurologists reviewed the data and examined the participant, rendering a probable diagnosis of dementia/non-dementia diagnosis. MDS-COGS results were compared with the neurologists' determination. SETTING: Fourteen RC/AL facilities in North Carolina. PARTICIPANTS: Data were collected from 50 staff on 166 residents without a diagnosis of dementia. MEASUREMENTS: In addition to the MDS-COGS, measures included a comprehensive neuropsychological battery. Depression and other neuropsychiatric symptoms were also assessed. RESULTS: Neurologists determined that 38% of participants had probable dementia. An MDS-COGS cutpoint of 2 was highly specific (0.97) but not very sensitive (0.49) for dementia. Test-retest and interrater agreement for a negative screen were high (88% and 93%, respectively). CONCLUSION: The MDS-COGS is a simple, brief screen that RC/AL staff can complete. It will identify with high specificity a subset of residents with undetected dementia, allowing rapid identification of those likely to need dementia care. Caution needs to be exercised in light of its low sensitivity, because some with milder dementia will not be detected. Further work is needed to determine whether staff can and will use the MDS-COGS as a trigger for more-thorough assessment and to guide care and improve outcomes.

Capacity issues and decision-making in dementia.

Capacity to make one's own decisions is fundamental to the autonomy of the individual. Capacity is a functional assessment made by a clinician to determine if a patient is capable of making a specific decision. Competency is a global assessment and legal determination made by a judge in court. Capacity evaluation for a patient with dementia is used to determine whether the patient is capable of giving informed consent, participate in research, manage their finances, live independently, make a will, and have ability to drive. Patients with dementia cannot be assumed to have impaired capacity. Even a patient with moderate or severe dementia, with obviously impaired capacity may still be able to indicate a choice and show some understanding. Four key components of decision-making in a capacity evaluation include understanding, communicating a choice, appreciation, and reasoning. Assessment of capacity requires a direct interview with the patient using open-ended questions and may include both informal and formal approaches depending on the situation and the context. A baseline cognitive evaluation with a simple test to assess executive function is often useful in capacity evaluation. All capacity evaluations are situation specific, relating to the particular decision under consideration, and are not global in scope. The clinician needs to spend adequate time with the patient and the family allaying their anxieties and also consider the sociocultural context. The area of capacity has considerable overlap with law and the clinician treating patients with dementia should understand the complexities of assessment and the implications of impaired capacity. It is also essential that the clinician be well informed and keep meticulous records. It is crucial to strike a balance between respecting the patient autonomy and acting in his/her best interest.

Relationship between Pelvic Alignment and Weight-bearing Asymmetry in Community-dwelling Chronic Stroke Survivors.

BACKGROUND AND PURPOSE: Altered pelvic alignment and asymmetrical weight bearing on lower extremities are the most common findings observed in standing and walking after stroke. The purpose of this study was to find the relationship between pelvic alignment and weight-bearing asymmetry (WBA) in community-dwelling chronic stroke survivors. MATERIALS AND METHODS: This cross-sectional study was conducted in tertiary care rehabilitation centers. In standing, the lateral and anterior pelvic tilt angle of chronic stroke survivors was assessed using palpation (PALM™) meter device. The percentage of WBA was measured with two standard weighing scales. Pearson correlation coefficient (r) was used to study the correlation between pelvic tilt and WBA. RESULTS: Of 112 study participants, the mean (standard deviation) age was 54.7 (11.7) years and the poststroke duration was 14 (11) months. The lateral pelvic tilt on the most affected side and bilateral anterior pelvic tilt were 2.47 (1.8) and 4.4 (1.8) degree, respectively. The percentage of WBA was 23.2 (18.94). There was a high correlation of lateral pelvic tilt with WBA (r = 0.631; P < 0.001) than anterior pelvic tilt (r = 0.44; P < 0.001). CONCLUSION: Excessive lateral pelvic tilt toward the most affected side in standing may influence the weight-bearing ability of the ipsilateral lower extremity in community-dwelling chronic stroke survivors.

Crossover balloon technique for vertebral artery thrombus: a novel method.

A 54-year-old man presented with recurrent episodes of transient ischemic attacks and acute stroke secondary to a floating thrombus in the right vertebral artery (VA) with narrowing of the right VA. He was initially treated medically with anticoagulation, antiplatelets and statins but developed multiple fresh infarcts. He was then referred for endovascular treatment, which was performed in a novel way.

Crossover balloon technique for vertebral artery thrombus: a novel method.

A 54-year-old man presented with recurrent episodes of transient ischemic attacks and acute stroke secondary to a floating thrombus in the right vertebral artery (VA) with narrowing of the right VA. He was initially treated medically with anticoagulation, antiplatelets and statins but developed multiple fresh infarcts. He was then referred for endovascular treatment, which was performed in a novel way.