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Clinical distinction between dementia with Lewy bodies (DLB) and late-onset Alzheimer's disease (AD) is difficult, while several features might affect the analyses of biomarkers. This study aimed to verify associations of anthropometric and demographic features with cerebrospinal fluid biomarkers, their ratios, and restructured traditional regression formulas in patients with DLB and AD, as well as in cognitively healthy controls. Consecutive outpatients with DLB were paired with outpatients with AD according to sex, dementia stage, and cognitive status, and with controls according to sex and age to investigate associations of sex, age, dementia duration, total sleep time, body mass index, alcohol use, smoking, sanitation, and APOE-ε4 alleles on the measurement of cerebrospinal fluid α-synuclein, biomarker ratios, and restructured traditional regression formulas involving amyloid-β (Aβ 42 ,Aβ 40 ,Aβ 38 ), tau, and phospho-tau Thr 181 . Overall, 81 participants were included with DLB (n = 27;11 APOE-ε4 +) or AD (n = 27;12 APOE-ε4 +), and controls (n = 27;4 APOE-ε4 +); two thirds were women. Cerebrospinal fluid evidence of amyloidosis and tauopathy was more prevalent among women with AD, while Aβ 42 /Aβ 38 could also discriminate men with DLB from men with AD. Restructured traditional regression formulas had higher diagnostic accuracy for women with AD. Aging, higher body mass index, and APOE-ε4 alleles were associated with amyloidosis in DLB, while only in AD were higher body mass index associated with lower tau pathology load, and more alcohol use associated with higher phospho-tau Thr 181 /Aβ 42 . These findings confirm the effects of anthropometric and demographic features on cerebrospinal fluid biomarkers, and also differences in aberrant amyloidosis and tauopathy between DLB and AD., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To investigate how language deteriorates over the Alzheimer's Disease course., Methods: A cross-sectional, observational study was carried out. 35 patients diagnosed with dementia due to AD using the NINCDS-ARDRA criteria and undergoing treatment for AD with a therapeutic dose of acetylcholinesterase inhibitors were assessed by the Boston Diagnostic Aphasia Examination (BDAE). The sample comprised 15 patients with mild AD (MMSE > 23, CDR = 0 or 0.5‒1.0) and 20 patients with moderate AD (MMSE = 13‒23, CDR = 2). The results for the 2 groups on all language tasks were compared., Results: A statistically significant difference was found between the mild and moderate AD groups for total score on the BDAE (95% CI 47.10‒114.08, t = 5.0, DF = 21, p = 0.000*), as well as on several tasks involving oral and writing comprehension, language oral expression and writing., Conclusion: The study results showed major changes in the moderate stage. Also, the decline in language performance correlated with the worsening of dementia syndrome, independently of sociodemographic variables., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 HCFMUSP. Published by Elsevier España, S.L.U. All rights reserved.)

Objective: In Alzheimer's disease (AD), angiotensin II receptor blockers (ARBs) could reduce cerebrovascular dysfunction, while angiotensin-converting enzyme inhibitors (ACEis) might increase brain amyloid-β by suppressing effects of the angiotensin-converting enzyme 1, an amyloid-β-degrading enzyme. However, ACEis could benefit patients with AD by reducing the amyloidogenic processing of the amyloid precursor protein, by central cholinergic and anti-inflammatory mechanisms, and by peripheral modulation of glucose homeostasis. We aimed to investigate whether the ACE insertion/deletion polymorphism is associated with clinical changes in patients with AD, while considering apolipoprotein E ( APOE )-ϵ4 carrier status and blood pressure response to angiotensin modulators., Methods: Consecutive outpatients with late-onset AD were screened with cognitive tests and anthropometric measurements, while their caregivers were queried for functional and caregiver burden scores. Prospective pharmacogenetic associations were estimated for 1 year, taking APOE -ϵ4 carrier status and genotypes of the ACE insertion/deletion polymorphism into account, along with treatment with ACEis or ARBs., Results: For 193 patients (67.4% women, 53.4% APOE -ϵ4 carriers), the ACE insertion/deletion polymorphism was in Hardy-Weinberg equilibrium ( p = 0.281), while arterial hypertension was prevalent in 80.3% ( n = 124 used an ACEi, n = 21 used an ARB). ARBs benefitted mostly APOE -ϵ4 carriers concerning caregiver burden variations, cognitive and functional decline. ACEis benefitted APOE -ϵ4 non-carriers concerning cognitive and functional decline due to improved blood pressure control in addition to possible central mechanisms. The ACE insertion/deletion polymorphism led to variable response to angiotensin modulators concerning neurological outcomes and blood pressure variations., Conclusion: Angiotensin modulators may be disease-modifiers in AD, while genetic stratification of samples is recommended in clinical studies.

Introduction: Phonetic-phonological impairments have been described in dementia due to Alzheimer's disease (AD). However, whether the likely phonological-linguistic changes progress with the evolution of the disease or whether phonetic-motor manifestations occur in all three stages of AD (mild, moderate, and severe) has not yet been clarified. Thus, the aim of this study was to verify whether phonological-linguistic and phonetic-motor speech manifestations occur in the mild, moderate, and severe stages of AD., Methods: Thirty participants in each stage of probable AD (mild, moderate, and severe) and 30 healthy older adults underwent cognitive, instrumental activities of daily living and phonetic-phonological assessments. Phonetic-phonological manifestations were classified into three types: likely phonetic-motor, likely phonological-linguistic, and manifestations that may occur in disorders of both phonetic and phonological origin., Results: The manifestations analyzed in this study occurred rarely. The manifestations that may occur in disorders of both phonetic and phonological origin were the most common in all stages of the disease. The likely phonetic-motor manifestations emerged during the mild stage of the disease (distortions, prolonged intersegment duration, and vowel prolongations), while the likely phonological-linguistic manifestations were present mainly in the moderate (substitutions and attempts at the word level) and severe stages (substitutions, attempts at the word level, self-corrections, and anticipations). The occurrence of phonetic-phonological manifestations increased with disease progression., Conclusions: The type of phonological and phonetic manifestations in the individuals with AD differed according to the dementia stage and were statistically more frequent as dementia worsened., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Aim: To explore associations of cerebrospinal fluid biomarkers of neurodegeneration and amyloidosis with caregiver burden, cognition and functionality in dementia with Lewy bodies (DLB) paired with late-onset Alzheimer's disease (AD) and healthy older people., Methods: Consecutive outpatients with DLB were matched with outpatients with AD according to sex, cognitive scores and dementia stage, and with cognitively healthy controls according to age and sex to investigate associations of cerebrospinal fluid amyloid-β (Aβ 42 ,Aβ 40 ,Aβ 38 ), tau, phospho-tau Thr 181 , ubiquitin, α-synuclein and neurofilament light with caregiver burden, functionality, reverse digit span, a clock drawing test, Mini-Mental State Examination (MMSE) and Severe MMSE, adjusted for sex, age, education, dementia duration and APOE-ε4 alleles., Results: Overall, 27 patients with DLB (78.98 ± 9.0 years-old; eleven APOE-ε4 +) were paired with 27 patients with AD (81.50 ± 5.8 years-old; twelve APOE-ε4 +) and 27 controls (78.98 ± 8.7 years-old; four APOE-ε4 +); two-thirds were women. In AD, Aβ 42 /Aβ 38 and Aβ 42 were lower, while tau/Aβ 42 and phospho-tau Thr 181 /Aβ 42 were higher; α-synuclein/Aβ 42 was lower in DLB and higher in AD. The following corrected associations remained significant: in DLB, instrumental functionality was inversely associated with tau/phospho-tau Thr 181 and tau/Aβ 42 , and reverse digit span associated with α-synuclein; in AD, instrumental functionality was inversely associated with neurofilament light, clock drawing test scores inversely associated with phospho-tau Thr 181 /Aβ 42 and α-synuclein/Aβ 42 , and Severe MMSE inversely associated with tau/Aβ 42 and tau/phospho-tau Thr 181 ., Conclusions: Cerebrospinal fluid phospho-tau Thr 181 in DLB was similar to AD, but not Aβ 42 . In associations with test scores, biomarker ratios were superior to isolated biomarkers, while worse functionality was associated with axonal degeneration only in AD., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Till present, only a few countries have developed support programs for caregivers and families of patients with dementia aimed to improve knowledge, skills, and strategies to deal with the patient's symptoms. However, prior to offering this special support, it is important to identify beliefs and thoughts shared by informants related to cognition in elderly people. Questionnaires are instruments that allow having this information, such as the Knowledge of Memory Aging Questionnaire (KMAQ), which was designed to assess normal and pathological changes in the aging process., Objective: The aim of this study was to assess the knowledge about cognition, aging, and dementia as evaluated by the KMAQ in people who are in contact with elderly people, with and without cognitive impairment., Methods: A total of 78 relatives and caregivers of elderly patients were classified into two groups: group 1: relatives of patients with dementia (n1=48), and group 2: relatives of patients without cognitive impairment (n2=30). They were asked to answer some questionnaires about dementia, including the KMAQ., Results: Comparing the questionnaire's scores for normal cognitive changes items (g1: 0.53 vs. g2: 0.53, p-value: 0.99) did not show differences between the knowledge in both groups, nor shows the scores for pathological cognitive changes items (g1: 0.55 vs. g2: 0.55, p-value: 0.969)., Conclusions: It seems that being in contact with dementia does not improve knowledge about it. Knowledge of normal changes in cognition could make it possible to recognize "red flags" suggestive of neurodegenerative processes, allowing for earlier diagnosis and more options for treatment., Competing Interests: Disclosure: The authors report no conflicts of interest.

Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB) represent the second most common type of degenerative dementia in patients aged 65 years and older, leading to progressive cognitive dysfunction and impaired quality of life. This study aims to provide a consensus based on a systematic Brazilian literature review and a comprehensive international review concerning PDD and DLB. Moreover, we sought to report on and give recommendations about the best diagnostic approaches focusing on primary and secondary care. Based on the available data, we recommend clinicians to apply at least one brief global cognitive instrument to assess PDD, such as the Mini-Mental State Examination and preferably the Montreal Cognitive Assessment and the Addenbrooke's Cognitive Examination-Revised. Validated instruments to accurately assess functional abilities in Brazilian PD patients are still incipient. Further studies should focus on biomarkers with Brazilian cohorts., Competing Interests: Conflito de interesses: : JS: Participação como palestrante em simpósios promovidos pelo laboratório Roche; LPS: Participação no conselho consultivo da Biogen. Participação como palestrante em simpósios promovidos pelos laboratórios Aché, Apsen e Biogen; MLFB: Participação no conselho consultivo da Biogen. Desenvolvimento de material para educação médica continuada e participação como palestrante em simpósios promovidos pelos laboratórios EMS e Torrent; PC: Participação como investigador principal em ensaios clínicos para os laboratórios Novo Nordisk e Roche. Participação no conselho consultivo dos laboratórios Aché, Biogen, EMS, Nutricia e Roche. Desenvolvimento de material para educação médica continuada e participação como palestrante em simpósios promovidos pelos laboratórios Aché, Nutricia, Libbs, Roche, Sandoz, Torrent e Zodiac; PHFB: Participação no conselho consultivo dos laboratórios Biogen e Novo Nordisk. Supervisão de atividades de treinamento nos laboratórios Biogen, Janssen-Cilag e Novo Nordisk e para a Quintiles. Participação como palestrante em simpósios promovidos pelos laboratórios Apsen, Nutricia, Roche e Sandoz; LCS: Participação no conselho consultivo da Biogen. Participação como palestrante em simpósios promovidos pela Biogen; RN: Participação no conselho consultivo da Biogen; JBP, VT, HBF, MS, MTB, BJAPB, FACV, MLFG, SMDB, RMC, NAFF: Não há conflito de interesse a declarar.

Since the publication of the latest recommendations for the diagnosis and treatment of Vascular Dementia by the Brazilian Academy of Neurology in 2011, significant advances on the terminology and diagnostic criteria have been made. This manuscript is the result of a consensus among experts appointed by the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology (2020-2022). We aimed to update practical recommendations for the identification, classification, and diagnosis of Vascular Cognitive Impairment (VCI). Searches were performed in the MEDLINE, Scopus, Scielo, and LILACS databases. This guideline provides a comprehensive review and then synthesizes the main practical guidelines for the diagnosis of VCI not only for neurologists but also for other professionals involved in the assessment and care of patients with VCI, considering the different levels of health care (primary, secondary and tertiary) in Brazil., Competing Interests: Conflito de interesses: : JS: Participação como palestrante em simpósios promovidos pelo laboratório Roche; LPS: Participação no conselho consultivo da Biogen. Participação como palestrante em simpósios promovidos pelos laboratórios Aché, Apsen and Biogen; MLFB: Participação no conselho consultivo da Biogen. Desenvolvimento de material para educação médica continuada e participação como palestrante em simpósios promovidos pelos laboratórios EMS e Torrent; PC: Participação como investigador principal em ensaios clínicos para os laboratórios Novo Nordisk e Roche. Participação no conselho consultivo dos laboratórios Aché, Biogen, EMS, Nutricia e Roche. Desenvolvimento de material para educação médica continuada e participação como palestrante em simpósios promovidos pelos laboratórios Aché, Nutricia, Libbs, Roche, Sandoz, Torrent e Zodiac; PHFB: Participação no conselho consultivo dos laboratórios Biogen e Novo Nordisk. Supervisão de atividades de treinamento nos laboratórios Biogen, Janssen-Cilag e Novo Nordisk e para a Quintiles. Participação como palestrante em simpósios promovidos pelos laboratórios Apsen, Nutricia, Roche e Sandoz; LCS: Participação no conselho consultivo do laboratório Biogen. Participação como palestrante em simpósios promovidos pelo laboratório Biogen; RN: Participação no conselho consultivo do laboratório Biogen; BJAPB, JISN, GSA, FKS, CKS, FTM, NAFF, FACV, SMDB, EE, MLFC: There is no conflict of interest to declare.

"Frontotemporal dementia" (FTD) is a clinical syndrome characterized by the focal involvement of the frontal and/or temporal lobes. FTD has three clinical phenotypes: the behavioral variant and two linguistic subtypes, namely, non-fluent/agrammatic primary progressive aphasia (PPA-NF/A) and semantic PPA (PPA-S). FTD is the second most common cause of dementia in individuals under the age of 65 years. This article presents recommendations for the diagnosis of FTD in the Brazilian scenario, considering the three levels of complexity of the health system: primary health care, secondary and tertiary levels. Diagnostic guidelines are proposed, including cognitive testing, behavioral and language assessments, laboratory tests, and neuroimaging., Competing Interests: Conflito de interesses: : LCS: Participação no conselho consultivo do laboratório Biogen. Participação como palestrante em simpósios promovidos pelo laboratório Biogen; JS: Participação como palestrante em simpósios promovidos pelo laboratório Roche; LPS: Participation in advisory boards for Biogen. Participação como palestrante em simpósios promovidos pelos laboratórios Aché, Apsen e Biogen; MLFB: Participation in advisory boards for Biogen. Desenvolvimento de material para educação médica continuada e participação como palestrante em simpósios promovidos pelos laboratórios EMS e Torrent; PC: Participação como investigador principal em ensaios clínicos para os laboratórios Novo Nordisk e Roche. Participação nos conselhos consultivos dos laboratórios Aché, Biogen, EMS, Nutricia e Roche. Desenvolvimento de material para educação médica continuada e participação como palestrante em simpósios promovidos pelos laboratórios Aché, Nutricia, Libbs, Roche, Sandoz, Torrent e Zodiac; PHFB: Participação nos conselhos consultivos dos laboratórios Biogen e Novo Nordisk. Supervisão de atividades de treinamento nos laboratórios Biogen, Janssen-Cilag e Novo Nordisk e para Quintiles. Participação como palestrante em simpósios promovidos pelos laboratórios Apsen, Nutricia, Roche e Sandoz; RN: Participação no conselho consultivo do laboratório Biogen; MLH, THM, MTCG, MSY, BJAPB, NAFF, FACV, MLFC, SMDB, VSB, LTT: There is no conflict of interest to declare.

There is currently no cure for neurodegenerative or vascular dementias, but some pharmacological and non-pharmacological interventions may contribute to alleviate symptoms, slow disease progression and improve quality of life. Current treatment approaches are based on etiology, symptom profile and stage of dementia. This manuscript presents recommendations on pharmacological and non-pharmacological treatments of dementia due to Alzheimer's disease, vascular cognitive impairment, frontotemporal dementia, Parkinson's disease dementia, and dementia with Lewy bodies., Competing Interests: Conflito de interesses: : PC: Participação como investigador principal em ensaios clínicos patrocinados pelos laboratórios Novo Nordisk e Roche. Atividades de consultoria para os laboratórios Aché, Biogen, EMS, Nutricia e Roche. Desenvolvimento de material para educação médica continuada e participação como palestrante em simpósios patrocinados pelos laboratórios Aché, Nutricia, Libbs, Roche, Sandoz, Torrent e Zodiac; VM: Desenvolvimento de material para educação médica continuada e participação como palestrante em simpósios patrocinados pelos laboratórios Biogen, Sandoz e Torrent; JS: Participação como palestrante em simpósios patrocinado pelo laboratório Roche; LPS: Atividades de consultoria para o laboratório Biogen. Participação como palestrante em simpósios patrocinados pelos laboratórios Aché, Apsen e Biogen; MLFB: Atividades de consultoria para o laboratório Biogen. Desenvolvimento de material para educação médica continuada e participação como palestrante em simpósios patrocinados pelos laboratórios EMS e Torrent; PHFB: Atividades de consultoria para os laboratórios Biogen e Novo Nordisk. Supervisão das atividades de treinamento para os laboratórios Biogen, Janssen-Cilag e Novo Nordisk, e para a Quintiles. Participação como palestrante em simpósios patrocinados pelos laboratórios Apsen, Nutricia, Roche e Sandoz; LCS: Atividades de consultoria para o laboratório Biogen. Participação como palestrante em simpósios patrocinados pela Biogen; RN: Participação no conselho consultivo do laboratório; JL, MVDC, FS, EFC, BJAPB, NAFF, FACV, MLFC, SMDB, HBD: Não há conflito de interesse a declarar.

This consensus, performed by the Brazilian Academy of Neurology (BAN) will approach practically how to evaluate patients with cognitive complaints and how to clinically and etiologically diagnose the three clinical syndromes associated with the different stages of cognitive decline: subjective cognitive decline (SCD), mild cognitive impairment (MCI), and dementia. This BAN consensus discusses SCD diagnosis for the first time, updates MCI and dementia diagnoses, recommends the adequate cognitive tests and the relevant etiological work-up and care of patients with cognitive decline at different levels of care within the Brazilian Unified Health System. We also review the main assessment instruments used in Brazil and Latin America., Competing Interests: Conflito de interesses: : JS: Participação como palestrante em simpósios promovidos pelo laboratório Roche; LPS: Participação em conselhos consultivos da Biogen. Participação como palestrante em simpósios promovidos pelos laboratórios Aché, Apsen e Biogen; MLFB: Participação em conselhos consultivos da Biogen. Desenvolvimento de material para educação médica continuada e participação como palestrante em simpósios promovidos pelos laboratórios EMS e Torrent; PC: Participação como investigador principal em ensaios clínicos para os laboratórios Novo Nordisk e Roche. Participação em conselhos consultivos para os laboratórios Aché, Biogen, EMS, Nutricia e Roche. Desenvolvimento de material para educação médica continuada e participação como palestrante em simpósios promovidos pelos laboratórios Aché, Nutricia, Libbs, Roche, Sandoz, Torrent e Zodiac; PHFB: Participação em conselhos consultivos para os laboratórios Biogen e Novo Nordisk. Supervisão das atividades de treinamento para os laboratórios Biogen, Janssen-Cilag e Novo Nordisk e para a Quintiles. Participação como palestrante em simpósios promovidos pelos laboratórios Apsen, Nutricia, Roche e Sandoz; EPFR: Alzheimer’s Association, World Federation of Neurology and National Institute of Health (concessão número R21AG069252); LCS: Participação no conselho consultivo do laboratório Biogen. Participação como palestrante em simpósios promovidos pelo laboratório Biogen; RN: Participação no conselho consultivo do laboratório Biogen; KGCF, MCND, RK, ASN, BJAPB, NAFF, MLFC, SMDB, FACV: Não há conflito de interesse a declarar.

Alzheimer's disease (AD) and other neurodegenerative dementias have a progressive course, impairing cognition, functional capacity, and behavior. Most studies have focused on AD. Severe dementia is associated with increased age, higher morbidity-mortality, and rising costs of care. It is fundamental to recognize that severe dementia is the longest period of progression, with patients living for many years in this stage. It is the most heterogeneous phase in the process, with different abilities and life expectancies. This practice guideline focuses on severe dementia to improve management and care in this stage of dementia. As it is a long period in the continuum of dementia, clinical practice should consider non-pharmacological and pharmacological approaches. Multidisciplinary interventions (physical therapy, speech therapy, nutrition, nursing, and others) are essential, besides educational and support to caregivers., Competing Interests: Conflito de interesses: : JS: Participação como palestrante em simpósios promovidos pelo laboratório Roche; LPS: Participação no conselho consultivo da Biogen. Participação como palestrante em simpósios promovidos pelos laboratórios Aché, Apsen e Biogen; MLFB: Participação no conselho consultivo da Biogen. Desenvolvimento de material para educação médica continuada e participação como palestrante em simpósios promovidos pelos laboratórios EMS e Torrent; PC: Participação como investigador principal em ensaios clínicos para os laboratórios Novo Nordisk e Roche. Participação no conselho consultivo do laboratório Aché, Biogen, EMS, Nutricia e Roche. Desenvolvimento de material para educação médica continuada e participação como palestrante em simpósios promovidos pelos laboratórios Aché, Nutricia, Libbs, Roche, Sandoz, Torrent e Zodiac; PHFB: Participação nos conselhos consultivos dos laboratórios Biogen e Novo Nordisk. Supervisão das atividades de treinamento para os laboratórios Biogen, Janssen-Cilag e Novo Nordisk e para a Quintiles. Participação como palestrante em simpósios promovidos pelos laboratórios Apsen, Nutricia, Roche e Sandoz; LCS: Participação no conselho consultivo da Biogen. Participação como palestrante em simpósios promovidos pela Biogen; RN: Participação no conselho consultivo do laboratório Biogen; SMDB, IP, WVB, VC, CELF, BJAPB, NAFF, FACV, MLFC, RRS, LSM: Não há conflito de interesse a declarar.

This paper presents the consensus of the Scientific Department of Cognitive Neurology and Aging from the Brazilian Academy of Neurology on the diagnostic criteria for Alzheimer's disease (AD) in Brazil. The authors conducted a literature review regarding clinical and research criteria for AD diagnosis and proposed protocols for use at primary, secondary, and tertiary care levels. Within this clinical scenario, the diagnostic criteria for typical and atypical AD are presented as well as clinical, cognitive, and functional assessment tools and complementary propaedeutics with laboratory and neuroimaging tests. The use of biomarkers is also discussed for both clinical diagnosis (in specific conditions) and research., Competing Interests: Conflito de interesses: : LPS: Participação no conselho consultivo do laboratório Biogen. Participação como palestrante em simpósios promovidos pelos laboratórios Aché, Apsen e Biogen; MLFB: Participação no conselho consultivo do laboratório Biogen. Desenvolvimento de material para educação continuada e participação como palestrante em simpósios promovidos pelos laboratórios EMS e Torrent; JS: Participação como palestrante em simpósio promovido pelo laboratório Roche; PC: Participação como investigador principal em ensaios clínicos para os laboratórios Novo Nordisk e Roche. Participação no conselho consultivo dos laboratórios Aché, Biogen, EMS, Nutricia e Roche. Desenvolvimento de material para educação continuada e participação como palestrante em simpósios promovidos pelos laboratórios Aché, Nutricia, Libbs, Roche, Sandoz, Torrent e Zodia; PHFB: Participação em advisory boards dos laboratórios Biogen e Novo Nordisk. Supervisão das atividades de treinamento para os laboratórios Biogen, Janssen-Cilag e Novo Nordisk e para a Quintiles. Participação como palestrante em simpósios promovido pelos laboratórios Apsen, Nutricia, RN: Participação no conselho consultivo do laboratório Biogen; Roche e Sandoz; LCS: Participação no conselho consultivo do laboratório Biogen. Participação como palestrante em simpósios promovidos pelo laboratório Biogen. MR, OVF, MLS, BJAPB, NAFF, FACV, MLFC, SMDB, BPD, : declaram não haver conflito de interesse.

Objective: Neuropsychiatric syndromes have been associated with memory dysfunction and risk of and earlier onset of dementia, but how psychotropic drugs affect clinical changes in Alzheimer's disease is not entirely clear. This study aimed to assess the prospective effects of psychotropic drugs on cognitive and functional changes in Alzheimer's disease according to APOE ε4 carrier status., Methods: The study included consecutive outpatients with late-onset Alzheimer's disease (N=193) and examined score variations at 1 year on the following tests: Clinical Dementia Rating sum of boxes, Mini-Mental State Examination, Severe Mini-Mental State Examination (SMMSE), Brazilian version of the Zarit Caregiver Burden Interview, Index of Independence in Activities of Daily Living, and Lawton's Instrumental Activities of Daily Living Scale. Analyses of score variations accounted for the use of psychotropic drugs or the number of different medications in use, as well as APOE ε4 carrier status, with significance at p<0.05., Results: For APOE ε4 noncarriers (N=90), cholinesterase inhibitors were beneficial regarding caregiver burden (p=0.030) and basic functionality (p=0.046), memantine was harmful regarding SMMSE score changes (p=0.032), second-generation antipsychotics had nonsignificant harmful effects on SMMSE score changes (p=0.070), and antiepileptic therapy (p=0.001) and the number of different medications in use (p=0.006) were harmful in terms of basic functionality. APOE ε4 carriers (N=103) did not experience any effects of isolated psychotropic drugs on clinical changes, including antidepressants., Conclusions: Results support the harmful prospective effects of second-generation antipsychotics and antiepileptic drugs on cognitive and functional changes in Alzheimer's disease, particularly for APOE ε4 noncarriers, whereas antidepressants may be safer options for behavioral enhancement.

Background: Pharmacogenetic effects of statins on clinical changes in Alzheimer's disease (AD) could be mediated by epistatic interactions among relevant genetic variants involved in cholesterol metabolism., Objective: To investigate associations of HMGCR (rs3846662), NR1H2 (rs2695121), or CETP (rs5882&rs708272) with cognitive and functional changes in AD, with stratification according to APOEɛ4 carrier status and lipid-lowering treatment with lipophilic statins., Methods: Consecutive outpatients with late-onset AD were screened with cognitive tests, while caregivers scored functionality and global ratings, with prospective neurotranslational associations documented for one year., Results: Considering n = 190:142 had hypercholesterolemia, 139 used lipophilic statins; minor allele frequencies were 0.379 (rs2695121-T:46.3% heterozygotes), 0.368 (rs5882-G:49.5% heterozygotes), and 0.371 (rs708272-A:53.2% heterozygotes), all in Hardy-Weinberg equilibrium. For APOEɛ4 carriers: rs5882-GG protected from cognitive decline; rs5882-AA caused faster cognitive decline; carriers of rs2695121-CC or rs5882-AA were more susceptible to harmful cognitive effects of lipophilic statins; carriers of rs5882-GG or rs708272-AG had functional benefits when using lipophilic statins. APOEɛ4 non-carriers resisted any cognitive or functional effects of lipophilic statins, while invariability of rs3846662 (all AA) prevented the assessment of HMGCR effects. When assessing CETP haplotypes only: rs5882-GG protected from cognitive and functional decline, regardless of lipophilic statin therapy; lipophilic statins usually caused cognitive and functional harm to carriers of rs5882-A and/or rs708272-A; lipophilic statins benefitted cognition and functionality of carriers of rs5882-G and/or rs708272-G., Conclusion: Reportedly protective variants of CETP and NR1H2 also slowed cognitive and functional decline particularly for APOEɛ4 carriers, and regardless of cholesterol variations, while therapy with lipophilic statins might affect carriers of specific genetic variants.

Background: Digital technologies (digiTech) enhance benefits in healthcare and are present in elderly people lives. Healthcare professionals (HCP) who deal with dementia and related disorders face enormous challenges in delivering healthcare using digital devices, and Covid-19 pandemic showed these pitfalls should be addressed. Technology solutions in elder people are being developed, not every HCP is heard, and we lack information about what these professionals think about this., Methods: Using structured questionnaires and asynchronous electrotonic data capture, we asked experienced (84.3% postgraduate degrees) HCP with different backgrounds (8 practice areas) about what they think of technology use among their patients and carers. The average person in our sample (N = 51) was a highly skilled (22.2 study-years) female (70.6%) medical doctor (62.8%) aged 39.1 years old (27 to 77 years), highly exposed to digiTech (68.6% mobile devices usage ≥4 hours/day). Neurologists (37.3%), neuropsychologists (15.7%), psychiatrists (13.7%), geriatricians (11.8%) were the most represented groups. This observational cross-sectional study is part of a Brazilian pilot study to explore technology usage in higher risk dementia adults (DigiTAU Project)., Results: Although HCP consider asking patients and carers about technology use to be theoretically important (90.2%) and useful in practice (94.2%), they often do not do it (45.1%). There is incongruity when they feel safe to offer interventions by digital means (58.8%) but commonly agree, on average, that HCP are not prepared to use digiTech (51.0%). Despite having positive views towards benefits in adopting digiTech for patients (98.1%), they think they bring more benefits to families and caregivers than to patients themselves (56.9%). HCP consider digiTech will change their practice in the short term within 1 year (58.8%) and within 5 years (88.3%). None of the 8 options suggested as the most "promising" technology in 10 years reaches more than 25% of the choices., Conclusions: HCP have conflicting views about the usage of technologies by their patients and caregivers but expect some positive changes in their work practice. It suggests new digiTech must be submitted to scrutiny so that its applicability overcomes the challenges. Further studies and analysis are needed to understand better this data., (© 2021 the Alzheimer's Association.)

Introduction: The inherited risk of late-onset Alzheimer's disease (AD) is genetically determined. We aimed to examine associations of genetic variants of APOE and ACE with age at AD onset and with neuropsychiatric symptoms according to each dementia stage. Methods: Consecutive outpatients with AD were assessed for demographic features, Clinical Dementia Rating scores, and the 10-item Neuropsychiatric Inventory, and genotyped for rs7412 and rs429358 ( APOE haplotypes, Real-Time Polymerase Chain Reactions), and the ACE insertion/deletion polymorphism (Polymerase Chain Reactions). Combined genetic variants of APOE and ACE were associated with age at dementia onset, and with neuropsychiatric symptoms in each dementia stage (adjusted for sex and age at dementia onset). Results: Over two-thirds of the 238 patients were women, whereas the mean age at dementia onset was 73.82 ± 6.2 years-old. APOE -ϵ4/ϵ4 carriers had earlier dementia onset ( p <.001). The ACE insertion/deletion polymorphism was in Hardy-Weinberg equilibrium ( p =.37) but was not associated with age at dementia onset, regardless of APOE -ϵ4 carrier status. The only results that survived corrections for false discovery rates were higher scores of dysphoria for APOE -ϵ4 carriers ( n =122) who also carried ACE deletion/deletion ( p =.031). No results survived corrections for false discovery rates for APOE -ϵ4 non-carriers ( n =116). Conclusions: Though only the APOE -ϵ4/ϵ4 haplotype affected AD onset, effects of the ACE insertion/deletion polymorphism over behavioural features might differ according to APOE -ϵ4 carrier status in genetic associations.

Relatives and caregivers receive little information and have poor knowledge about cognitive impairment and dementia., Objective: This study aimed to identify beliefs about cognitive impairment and aging among people who are in contact with older people with and without cognitive impairment, hypothesizing that the fact of being a close relative influences or modifies these beliefs., Methods: Seventy-eight participants were classified into two groups; group 1: relatives of patients with cognitive impairment or dementia from a behavioral neurology outpatient clinic (n 1 =48); and group 2: relatives of patients without objective cognitive impairment from different services of a geriatric outpatient clinic (n 2 =30). All subjects were asked to answer a questionnaire containing single choice and true/false questions about causes and risk factors for dementia., Results: Participants were mainly females and first-degree relatives. No statistical differences were observed for age, schooling, or follow-up time between groups. Participants recognized Alzheimer's disease as the main cause of memory loss in older adults (group 1=34 vs. group 2=15); when asking about sources of information about cognitive impairment, the three more common answers were doctors and health professionals , Internet , and journals/books . Group 1 got higher scores on questions about causes and risk factors for dementia, but no statistical differences were found., Conclusions: Dementia literacy is low even among the people in contact with this syndrome; caring for someone with dementia changes the concepts about memory and aging but only in a small proportion. Educational strategies to deal with misinformation can help to control risk factors and reduce the incidence of dementia., Competing Interests: Disclosure: The authors report no conflicts of interest.

Background: During the moderate stage of dementia due to Alzheimer's disease (AD), language disorder is more evident and it impacts on communication. An overview of language impairment could be helpful to find compensatory communication strategies for these patients., Objective: To identify all language impairments among patients with moderate-stage of AD., Methods: 20 patients diagnosed with probable AD based on the criteria of the NINCDS-ARDRA, with a MMSE score of 13-23 points and CDR=2, who were undergoing treatment for AD with therapeutic doses of acetyl cholinesterase inhibitors, were assessed using the Boston Diagnostic Aphasia Examination (BDAE), a test that provides a broad assessment of language. The results were compared with the performance of a normal population., Results: The patients assessed in this study presented normal scores for oral and written word recognition, repetition, mechanics of writing, primer-level dictation and spelling to dictation but also had impairment at most levels of linguistic processing, in oral and written comprehension and production. In general, as expected, the tasks relying on access to the mental lexicon were most significantly affected. However, they performed well in the naming task, in which semantic cues were presented. Moreover, the patients assessed in this study had better performance in written comprehension tasks than in oral ones., Conclusion: The severity of the language impairments was not homogenous, with some linguistic abilities more impaired than others. The abilities that were found to be preserved can help to guide strategies for aiding in communication at this stage of AD.

Background: Behavioral features may reflect proteinopathies predicting pathophysiology in neurodegenerative diseases., Objective: We aimed to investigate associations of cerebrospinal fluid biomarkers of amyloidogenesis and neurodegeneration with neuropsychiatric features in dementia with Lewy bodies (DLB) compared with late-onset Alzheimer's disease (AD) and cognitively healthy people., Methods: Consecutive outpatients with DLB were paired with outpatients with AD according to sex, dementia stage, and cognitive scores, and with cognitively healthy controls according to sex and age to investigate associations of cerebrospinal fluid amyloid-β (Aβ)42, Aβ40, Aβ38, total tau, phospho-tau Thr181, α-synuclein, ubiquitin, and neurofilament light with neuropsychiatric features according to APOEɛ4 carrier status., Results: Overall, 27 patients with DLB (78.48±9.0 years old, eleven APOEɛ4 carriers) were paired with 27 patients with AD (81.00±5.8 years old, twelve APOEɛ4 carriers) and 27 controls (78.48±8.7 years old, four APOEɛ4 carriers); two thirds were women. Behavioral burden was more intense in DLB. Biomarker ratios reflecting amyloidogenesis and neurodegeneration in DLB were more similar to those in AD when patients carried APOEɛ4 alleles. After corrections for false discovery rates, the following associations remained significant: in DLB, dysphoria was associated with tauopathy and indirect measures of amyloidogenesis, while in AD, agitation, and night-time behavior disturbances were associated with tauopathy, and delusions were associated with tauopathy and indirect measures of amyloidogenesis., Conclusion: Biomarker ratios were superior to Aβ and tau biomarkers predicting neuropsychiatric symptoms when associations with isolated biomarkers were not significant. At the end, APOEɛ4 carrier status influenced amyloidogenesis and tau pathology in DLB and in AD, and axonal degeneration only in DLB.

Background: Swallowing and feeding problems may occur with the progression of behavioral variant frontotemporal dementia (bvFTD) and can impair the anticipatory and oral preparatory phases of swallowing., Objective: To characterize swallowing problems and the feeding situation of patients with bvFTD and to correlate the swallowing problems with functionality, executive functions, cognitive and behavioral features., Methods: Consecutive outpatients with bvFTD in mild, moderate and severe dementia stages were recruited along with their caregivers. Patients and caregivers were screened with the following scales: "Mini-Mental State Examination", "Severe Mini-Mental State Examination", "FTLD-modified Clinical Dementia Rating", "Neuropsychiatric Inventory", "Frontal Assessment Battery", "Index of Independence in Activities of Daily Living", "Swallowing Rating Scale" and "Assessment of Feeding and Swallowing Difficulties in Dementia"., Results: Overall, thirty patients with bvFTD were included along with their caregivers. Patients with bvFTD showed feeding and swallowing difficulties such as: messy to eat, passivity, coughing and choking, difficulty with some food consistencies and with specific food. Swallowing problems in bvFTD correlated with impaired functionality (p<0.05) and cognition (p<0.05), executive dysfunction (p<0.01) and behavioral features (p<0.01). Caregivers had great difficulty in managing the feeding situation during mealtime, with different characteristics in each dementia stage., Conclusion: Patients with bvFTD had inappropriate speed eating, passivity, coughing and choking starting in the mild dementia stage, and these problems worsen in the severe stage. Such difficulties affected caregiver performance during mealtime. The correlations indicated that swallowing difficulties tend to follow cognitive and behavioral decline in patients with bvFTD.

Effects of statins over clinical changes in Alzheimer's disease (AD) are usually non-significant, but epistatic interactions between genetic variants involved in cholesterol metabolism could be important for such effects. We aimed to investigate whether LDLR single-nucleotide polymorphisms rs11669576 (LDLR8), rs5930 (LDLR10), and rs5925 (LDLR13) are associated with cognitive and functional changes in AD, while also considering APOE haplotypes and lipid-lowering treatment with lipophilic statins for stratification. Consecutive outpatients with late-onset AD were screened with cognitive tests, while caregivers scored functionality and caregiver burden, with prospective neurotranslational correlations documented for 1 year. For 179 patients, minor allele frequencies were 0.078 for rs11669576-A (14.5% heterozygotes), 0.346 for rs5930-A (42.5% heterozygotes), and 0.444 for rs5925-C (56.4% heterozygotes), all in Hardy-Weinberg equilibrium; 134 patients had hypercholesterolemia, and 133 used lipophilic statins. Carriers of rs11669576-G had faster cognitive decline, while functional decline was slower for carriers of rs11669576-A who used lipophilic statins. APOE-ε4 carriers who also carried rs5930-AA had improved caregiver burden, while carriers of haplotypes that included rs5930-AG had worse cognitive and functional outcomes, though carriers of the A allele of rs5930 had better cognitive and functional response to lipophilic statins. APOE-ε4 non-carriers who carried rs5925-TT had slower cognitive decline, while lipophilic statins protected carriers of the other genotypes. We preliminarily conclude that reportedly protective variants of LDLR and APOE against risk of AD also slowed cognitive decline, regardless of cholesterol variations, while therapy with lipophilic statins might benefit carriers of specific genetic variants.

Objective: Differential diagnosis between Parkinson's disease (PD) dementia and dementia with Lewy bodies (DLB) is difficult due to common features, whereas management decisions and research endpoints depend upon knowledge of dementia severity. We aimed to assess risk factors for age at dementia onset, as well as which neuropsychiatric features are associated with pharmacotherapy and signs and symptoms of Lewy body dementia., Patients and Methods: Patients with PD dementia or DLB were evaluated for age at disease onset, education, sanitation, anthropometric measures, alcohol use, smoking, history of infections or head trauma with unconsciousness, family history of neurodegenerative diseases, functional independence, cognition, behavior, motor features, caregiver burden and pharmacotherapy., Results: Fifty-one patients were recruited (37 with DLB, 14 with PD dementia). Cumulative alcohol use and married status were associated with earlier dementia onset, whereas history of treated systemic infections and cumulative family history of primary neurodegenerative diseases led to later dementia onset. The length of dementia was shorter only for severely impaired patients who used anti-depressants, but not for users of cholinesterase inhibitors, while no behavioral symptom was associated with dopaminergic therapy. Night-time behavior disturbances were inversely associated with sleep satisfaction, while caregiver burden was more affected by depression and motor features. Non-motor symptoms were more burdensome for patients with DLB, while in PD dementia anxiety and dysphoria occurred when motor features were less burdensome., Conclusions: PD dementia and DLB are two phenotypes of the same pathological entity, differing mostly by the occurrence of parkinsonian signs. Predictors of dementia onset differ from other neurodegenerative diseases., (Copyright © 2020 Elsevier B.V. All rights reserved.)

This study is aimed to evaluating the underlying cognitive strategies used during Semantic Verbal Fluency (SVF) performance and comparing the differences between cognitively healthy controls (CHC), amnestic and amnestic-multiple domain mild cognitive impairment (a-MCI and a-md-MCI), Alzheimer's disease (AD), Lewy body dementia (LBD), and behavioral variant frontotemporal dementia (bvFTD). The cross-sectional study comprised 236 participants involving 78 CHC individuals, 33 a-MCI and 48 a-md-MCI, 39 AD, 22 LBD, and 16 bvFTD patients. Scores differed significantly when comparing CHC with dementia groups, showing medium to large variances. The best components in distinguishing between CHC and the dementia groups were the SVF-Total score and SVF-Cluster Size variables. CHC showed different performance in the SVF-Cluster Size variable compared with a-md-MCI, AD, and bvFTD; whereas, in the SVF-Mean Cluster Size, CHC differed from MCI's, AD, and LBD. The switching component displayed smaller capacity to differentiate between the clinical groups. The effect size was large comparing AD with bvFTD (1.267) and medium comparing AD with LBD (0.689) using the SVF-Cluster Size variable, but small using the other variables for the comparisons between dementia groups. Quanti-qualitative examination of the SVF may provide a valuable clue in distinguishing CHC from MCI and different dementia subtypes.

Background & Objectives: Neurodegeneration affects blood pressure variations, while renal function and cerebral perfusion are impaired by vascular risk factors. This study was aimed to estimate variations of measures of cardiovascular risk in Alzheimer's dementia by pharmacogenetic analyses of the effects of angiotensin-converting enzyme (ACE) inhibitors and statins., Methods: Consecutive patients were prospectively followed to study variations of creatinine clearance and blood pressure for one year, estimated by correlating the effects of ACE inhibitors with the ACE Alu I/D polymorphism and genotypes or haplotypes of rs1800764 or rs4291, and the effects of statins with LDLR (low-density lipoprotein receptor) genotypes or haplotypes of rs11669576 (exon 8) or rs5930 (exon 10), or genotypes of rs2695121 (liver X receptor β gene). Variations of the coronary heart disease (CHD) risk according to these cardiovascular measures were also explored., Results: All polymorphisms of the 193 patients were in Hardy-Weinberg equilibrium. Genetic determinants of cardiovascular effects affected the individual variability of the response to ACE inhibitors and statins. ACE inhibitors, but not statins, reduced blood pressure for all patients. ACE inhibitors protected carriers of alleles that supposedly decrease serum ACE levels (rs1800764-T, rs4291-A, Alu II) regarding creatinine clearance variations (P <0.005), but carriers of Alu DD (P <0.02), rs1800764-C (P <0.05), or rs4291-AT (P <0.04) showed better blood pressure lowering effects. The presence of rs2695121-T (P=0.007) or rs5930-A (P=0.039) was associated with systolic blood pressure lowering, whereas rs5930-AA was protective against decrease in creatinine clearance (P=0.019). Statins lowered creatinine clearance for carriers of rs2695121-CT (P=0.026)., Interpretation & Conclusions: Pharmacological response of blood pressure and creatinine clearance to ACE inhibitors and statins may be genetically mediated., Competing Interests: None

Introduction: Alzheimer's disease (AD) is a degenerative syndrome that impairs cognitive functioning, including speech and language. Discourse can be used to analyze language processing, which is organized into microlinguistic and macrolinguistic dimensions., Objectives: To identify the occurrence of changes in the macrolinguistic dimension of oral discourse in AD patients. Design: This was developed as a cross-sectional study. Setting: Outpatient clinic of the Behavioural Neurology Division of São Paulo Federal University., Participants: 121 elderly patients, with ≥ 4 years of education, divided into AD and comparison groups., Measurements: The subjects were asked to create a narrative based on seven figures that made up a story. The macrolinguistic aspects of the narratives were analyzed., Results: The performance of the AD group was inferior to that of the comparison group on content-related, no-content-related complete and incomplete propositions as well as macropropositions, main information units, appropriated local and global coherence, cohesive devices and all subtypes, cohesive errors and some of their subtypes. Global coherence, macropropositions and ellipsis subtype of cohesive devices were the variables that best differentiated the groups., Conclusions: Changes were observed in most aspects of the macrolinguistic dimension of oral discourse in patients with AD.

Background: Illiteracy, high cerebrovascular risk and copies of APOE-ϵ4 are risk factors for Alzheimer's disease dementia (AD). We aimed to investigate the impacts of gender, education, coronary heart disease (CHD) risk and creatinine clearance variations, body mass index (BMI) and APOE haplotypes over the rates of cognitive and functional decline of AD in one year., Methods: Consecutive outpatients with late-onset AD were assessed for gender, schooling, BMI and APOE haplotypes, variations in one year of creatinine clearance and Framingham projections of the 10-year absolute CHD risk, and prospective scores of the Mini-Mental State Examination (MMSE), the Clinical Dementia Rating Sum-of-Boxes (CDR-SOB), the Index of Independence in Activities of Daily Living (ADL) and Lawton's Scale for Instrumental Activities of Daily Living (IADL)., Results: For 191 patients, mean age at AD onset was 73.26 ± 6.4 years-old, earlier for APOE-ϵ4/ϵ4 carriers (p = 0.0039). For women, higher BMI led to improvements in CDR-SOB (β = -0.091; p = 0.037) and MMSE (β = 0.126; p = 0.017) scores, while increased creatinine clearance was associated with improvements in ADL (β = 0.028; p = 0.012) and MMSE (β = 0.043; p = 0.039) scores and higher schooling led to faster worsening of IADL (β = -0.195; p = 0.022) scores. No variables impacted cognitive or functional decline for men, whereas copies of APOE-ϵ4 and the CHD risk had no significant effects whatsoever., Conclusions: Higher BMI and creatinine clearance are protective regarding cognitive and functional decline for women, whereas higher cognitive reserve may lead to faster decline in instrumental functionality. APOE haplotypes affected the age at AD onset, but not cognitive or functional decline.

Background: While the angiotensin-converting enzyme degrades amyloid-β, angiotensinconverting enzyme inhibitors (ACEis) may slow cognitive decline by way of cholinergic effects, by increasing brain substance P and boosting the activity of neprilysin, and by modulating glucose homeostasis and augmenting the secretion of adipokines to enhance insulin sensitivity in patients with Alzheimer's disease dementia (AD). We aimed to investigate whether ACE gene polymorphisms rs1800764 and rs4291 are associated with cognitive and functional change in patients with AD, while also taking APOE haplotypes and anti-hypertensive treatment with ACEis into account for stratification., Methods: Consecutive late-onset AD patients were screened with cognitive tests, while their caregivers were queried for functional and caregiver burden scores. Prospective pharmacogenetic correlations were estimated for one year, considering APOE and ACE genotypes and haplotypes, and treatment with ACEis., Results: For 193 patients, minor allele frequencies were 0.497 for rs1800764 - C (44.6% heterozygotes) and 0.345 for rs4291 - T (38.9% heterozygotes), both in Hardy-Weinberg equilibrium. Almost 94% of all patients used cholinesterase inhibitors, while 155 (80.3%) had arterial hypertension, and 124 used ACEis. No functional impacts were found regarding any genotypes or pharmacological treatment. Either for carriers of ACE haplotypes that included rs1800764 - T and rs4291 - A, or for APOE4- carriers of rs1800764 - T or rs4291 - T, ACEis slowed cognitive decline independently of blood pressure variations. APOE4+ carriers were not responsive to treatment with ACEis., Conclusion: ACEis may slow cognitive decline for patients with AD, more remarkably for APOE4- carriers of specific ACE genotypes., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Objective: We evaluated neuropsychological tests to compare cognitive impairment between two types of multiple system atrophy: predominant parkinsonism (MSA-P) and predominant cerebellar ataxia (MSA-C)., Patients and Methods: This cross-sectional study included 14 patients diagnosed with MSA: four with MSA-C and ten with MSA-P. Presence of motor symptoms was determined by using the Unified Rating MSA Scale (URMSAS). Non-motor symptoms were evaluated by the Short Form Health Survey (SF-36), Scales for Outcomes in Parkinson's disease Autonomic (SCOPA-AUT), Hospital Anxiety and Depression Scale (HADS), and Beck Depression Inventory (BDI). Neuropsychological tests were used to evaluate general cognition, verbal and visual memory, working memory, constructional ability, visuospatial, language, and executive function., Results: The median age of the patients was 62 years, median disease duration was 3.5 years, and median education level was 10 years. The median Mini-Mental State Examination (MMSE) score was 26.5 points, and median Mattis Dementia Rating Scale (MDRS) score was 131.5. We compared the continuous data between the two MSA subtypes and observed that bodily pain reported in the quality of life questionnaire, SF-36, was worse in MSA-P (p<0.05), and attention function evaluated by MDRS was significantly lower in MSA-C than MSA-P (p<0.05)., Conclusion: Our comparative study of cognitive impairment in MSA-P and MSA-C showed that both groups had impaired executive and visuospatial functions, while the attention deficit was predominant only in MSA-C. These findings support the concept that cognitive deficit originates from striatofrontal dysfunction and cerebellar degeneration. Our study also suggests that cognitive impairment is relevant in MSA, and clinical neurologists should not neglect evaluation of these aspects in their daily clinical practice., (Copyright © 2017. Published by Elsevier B.V.)

Lifetime risk factors for cognitive and functional decline in Alzheimer's disease (AD) are not fully understood, and were prospectively evaluated in patients with low mean schooling from São Paulo, Brazil. Consecutive outpatients with late-onset AD were assessed for APOE haplotypes and the following potential baseline predictors: gender, schooling, age at dementia onset, lifetime urban living and sanitary conditions, occupational complexity, cognitive and physical activities, cerebrovascular risk factors (obesity, lifetime alcohol use and smoking, length of arterial hypertension, diabetes mellitus, and a dyslipidemic profile), use of a pacemaker, creatinine clearance, body mass index, waist circumference, head traumas with unconsciousness, treated systemic bacterial infections, amount of surgical procedures under general anesthesia, and family history of AD. Participants were followed from October 2010 to May 2017 for baseline risk factor associations with time since dementia onset for Clinical Dementia Rating and Mini-Mental State Examination score changes. For 227 patients (154 women, 119 APOE ε 4 carriers), later AD onset (mean 73.60±6.4 years-old, earlier for APOE ε 4/ε 4 carriers, p < 0.001) was the only variable hastening all endpoints, baseline creatinine clearance and lifetime alcohol use were hazardous for earlier cognitive and functional endpoints, women had earlier cognitive endpoints only, and schooling had a cumulative protective effect over later cognitive endpoints, particularly for carriers of APOE ε 4. Exclusively for carriers of APOE ε 4, head traumas with unconsciousness were hazardous for earlier cognitive endpoints, while lifetime sanitary conditions were protective regarding later cognitive endpoints. Functional and cognitive outcomes in AD represent probable interactions between effects of brain reserve and cerebral perfusion over neurodegeneration.

Background: Assigning a diagnosis to a patient with dementia is important for the present treatment of the patient and caregivers, and scientific research. Nowadays, the dementia diagnostic criteria are based on clinical information regarding medical, history, physical examination, neuropsychological tests, and supplementary exams and, therefore, subject to variability through time., Methods: A retrospective observational study to evaluate variables related to clinical diagnostic stability in dementia syndromes in at least one year follow up. From a sample of 432 patients, from a single university center, data were collected regarding sociodemographic aspects, Clinical Dementia Rating, physical examination, neuropsychological tests, and supplementary exams including a depression triage scale., Results: From this sample, 113 (26.6%) patients have their diagnosis changed, most of them adding a vascular component to initial diagnosis or depression as comorbidity or main disease. Our findings show that many factors influence the diagnostic stability including the presence of symmetric Parkinsonism, initial diagnosis of vascular dementia, presence of diabetes and hypertension, the presence of long term memory deficit in the neuropsychological evaluation, and normal neuroimaging. We discuss our findings with previous findings in the literature., Conclusion: Every step of the clinical diagnosis including history, vascular comorbidities and depression, physical examination, neuropsychological battery, and neuroimaging were relevant to diagnosis accuracy.

Hypercholesterolemia and statin use have been unevenly associated with clinical change in Alzheimer's disease dementia. In this longitudinal study, 192 consecutive outpatients with late-onset Alzheimer's disease dementia were stratified according to APOE haplotypes, and followed for one year to investigate associations of lipid profile variations and lipophilic statin therapy with changes in cognition, caregiver burden, basic and instrumental functionality. Overall, 102 patients (53.1%) carried APOE4+ haplotypes and 90 (46.9%) carried APOE4- haplotypes; 189 patients (98.4%) used either a cholinesterase inhibitor, or Memantine, or both; 144 patients had dyslipidemias and 143 of them received statin therapy. Total cholesterol, LDL-cholesterol, Mini-Mental State Examination scores, and functional independence scores were significantly lower at the end of the follow-up, while Clinical Dementia Rating sum-of-boxes scores were higher. Exclusively for APOE4- carriers, rising LDL-cholesterol levels were associated with a trend toward improvements in the Index of Independence in Activities of Daily Living (β=0.010; ρ=0.16), whereas rising HDL-cholesterol levels were associated with lowered scores (β=-0.051; ρ=0.04). Lipophilic statin therapy had non-significant protective effects over Clinical Dementia Rating sum-of-boxes score variations only for APOE4- carriers. APOE4- haplotypes might enhance lipid availability to protect neuronal membranes, thus overcoming their supposed dysfunction in cholesterol metabolism, while APOE4+ carriers have inefficient neural repair mechanisms. In conclusion, APOE haplotypes seem to influence the protective effects of lipid profile variations for patients with Alzheimer's disease dementia, but current evidence is insufficient to propose lipid-lowering drugs as specific anti-dementia therapy., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: More than 95% of right-handed individuals, as well as almost 80% of left-handed individuals, have left hemisphere dominance for language. The perisylvian networks of the dominant hemisphere tend to be the most important language systems in human brains, usually connected by bidirectional fibres originated from the superior longitudinal fascicle/arcuate fascicle system and potentially modifiable by learning. Neuroplasticity mechanisms take place to preserve neural functions after brain injuries. Language is dependent on a hierarchical interlinkage of serial and parallel processing areas in distinct brain regions considered to be elementary processing units. Whereas aphasic syndromes typically result from injuries to the dominant hemisphere, the extent of the distribution of language functions seems to be variable for each individual., Method: Review of the literature Results: Several theories try to explain the organization of language networks in the human brain from a point of view that involves either modular or distributed processing or sometimes both. The most important evidence for each approach is discussed under the light of modern theories of organization of neural networks., Conclusions: Understanding the connectivity patterns of language networks may provide deeper insights into language functions, supporting evidence-based rehabilitation strategies that focus on the enhancement of language organization for patients with aphasic syndromes.

Objectives: To assess correlations among gait apraxia, balance impairment and cognitive performance in mild (AD1, n = 30) and moderate (AD2, n = 30) AD., Method: The following evaluations were undertaken: gait apraxia (Assessment Walking Skills); balance performance (Berg Balance Scale); Clinical Dementia Rating and Mini-mental State Examination (MMSE)., Results: While disregarding AD subgroups, Berg Balance Scale and the MMSE correlated significantly with Assessment Walking Skills and 23% of all subjects scored below its cut-off. After stratification, Berg Balance Scale correlated significantly with Assessment Walking Skills in both AD subgroups, and with the MMSE only in AD1., Conclusions: Balance impairment does not necessarily coexist with gait apraxia. Gait apraxia is more prevalent in moderate AD when compared with mild AD.

Essential tremor (ET) was long believed to be a monosymptomatic disorder. However, studies have evidenced structural changes and attention is now being focused on non-motor symptoms. The objective of the study is to describe and compare ET patients with control groups according to their cognitive functions, and secondarily, to compare their sociodemographic characteristics and other clinical features. All participants were assessed using the Fahn-Tolosa-Marin Tremor Rating Scale for the severity of tremor; a neuropsychological assessment battery and a screening questionnaire for mood and anxiety symptoms. There were no significant age and gender differences between all groups. As for neuropsychological assessment results, a significant difference was found only in the Pegboard test. We also found a significant negative correlation between a poorer cognitive test results and disease severity and a significant differences regarding depression or anxiety symptoms in patients with ET. The study results suggest that patients with ET have impaired manual dexterity and attention.

Background: Few studies have described characteristics of swallowing in primary progressive aphasia (PPA) and its variants., Objective: To describe and characterize swallowing and eating behaviors of patients with PPA, as well as their correlates with neuropsychiatric symptoms and patterns of communication., Methods: We studied 16 patients with PPA and 16 their caregivers. PPA was subdivided in agrammatic variant (PPA-G), semantic variant (PPA-S) and logopenic variant (PPA-L). All patients and their caregivers were screened with the following scales: "Assessment of Feeding and Swallowing Difficulties in Dementia", "Neuropsychiatric Inventory", and "Functional Outcome Questionnaire for Aphasia"., Results: Patients with PPA-S had diverse swallowing problems such as drooling of saliva or food, multiple swallows, delayed swallow and choking, all of which correlated with anxiety, apathy and aberrant motor behavior. Patients with PPA-G and PPA-L had choking and delayed swallow, respectively. Disturbances in eating behaviors were more frequent in the group with PPA-L, and they correlated with difficulties in patterns of communication., Conclusions: All variants showed swallowing difficulties and they were more frequent in PPA-S. Further studies with larger samples of patients are needed to better characterize swallowing problems and their consequences in the different variants of PPA.

Background: Midlife hypertension followed by late life hypotension resulting from neurodegeneration increases amyloidogenesis and tauopathy., Methods: Consecutive outpatients with late-onset Alzheimer's disease (AD) at various stages and their respective caregivers were assessed for score variations in 1 year of tests assessing caregiver burden, functionality and cognition according to blood pressure (BP) variations and APOE haplotypes, while also taking into account differential effects of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, β-blockers, calcium channel blockers, diuretics, or no antihypertensive medication on score changes. The diagnosis and treatment of arterial hypertension followed the JNC 7 report., Results: Variations in systolic BP (-11.76 ± 17.1 mm Hg), diastolic BP (-4.92 ± 10.3 mm Hg) and pulse pressure (-6.84 ± 12.6 mm Hg) were significant after 1 year (n = 191; x03C1; < 0.01). For APOE4+ carriers, rises in systolic or diastolic BP improved Clinical Dementia Rating Scale Sum of Boxes scores (x03C1; < 0.04), with marginally significant improvements in Mini-Mental State Examination scores resulting from risen systolic (x03C1; = 0.069) or diastolic BP (x03C1; = 0.079), and in basic independence only regarding risen diastolic BP (x03C1; = 0.055). APOE4- carriers resisted any functional or cognitive effects of BP variations. No differences were found regarding any antihypertensive class for variations in BP or any test scores, regardless of APOE haplotypes., Conclusions: Targeting mild BP elevations brings better functional and cognitive results for APOE4+ carriers with AD., (© 2016 S. Karger AG, Basel.)

Midlife cerebrovascular risk, low cognitive reserve and APOE4+ haplotypes are risk factors for Alzheimer's disease dementia (AD). We prospectively searched for factors that might be associated with yearly changes in caregiver burden, cognition, basic and instrumental functionality in 193 consecutive outpatients with late-onset AD, namely gender, APOE haplotypes, schooling, age at AD onset, marital status, depression, cerebrovascular risk factors, serum TSH levels, cognitive and physical activities, and treatment with cholinesterase inhibitors or anti-psychotics, while also investigating associations between APOE haplotypes and patient participation in cognitive or physical activities. Higher education led to greater declines in instrumental functionality, whereas increases in body mass index were associated with rises in basic functionality and cognitive test scores. Established cerebrovascular risk factors had no independent effects over cognitive or functional change, but their combinations led to cognitive improvement, possibly related to enhanced cerebral perfusion in late life. Cholinesterase inhibitors improved caregiver burden. Enhanced instrumental functionality and steeper cognitive decline by the use of anti-psychotics might be attributed to improved behavioural symptoms and neuropsychiatric side effects, respectively. Each copy of APOE-ε4 (β=-0.102) led to cumulative decreased participation in physical activities (ρ=0.015). These results might impact public health policies and the interpretation of clinical trials for AD., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Aims: Primarily, we sought to verify correlations among assessments for cognition, behaviour and functional independence in a sample of patients with dementia due to Alzheimer's disease (AD). Secondarily, impacts of education, APOE haplotypes, length of dementia, age and alcohol use over the neuropsychiatric assessment were estimated., Methods: Patients with AD were assessed for demographic features, neuropsychiatric symptoms, cognitive test scores, functional impairment, caregiver burden and APOE haplotypes. Statistical comparisons were undertaken by way of Kruskal-Wallis test, linear regressions and Spearman correlations, significance at ρ < 0.05., Results: A total of 217 patients were included. Mean schooling was 4.21 ± 3.7 years, with significant impacts over cognitive tests. Mean age at examination was 78 ± 6.19 years-old, significantly influencing instrumental functionality. The mean length of the dementia syndrome was 5.4 ± 2.9 years, significantly impacting cognitive decline and functionality. Apathy was the most common behavioural symptom, negatively correlated with anxiety and delusions, and positively correlated with lifetime alcohol load. Patients with previous smoking or drinking habits were more likely to continue smoking or drinking later in life. APOE4+ haplotypes led to earlier dementia onset and significantly lower caregiver burden in mild dementia stages., Conclusions: Most correlations among test results were highly significant, confirming that cognition, behaviour and functionality are usually interrelated in all stages of AD. Caregiver burden was correlated with behaviour, but not with cognition, and was lower for patients with APOE4+ haplotypes in mild dementia stages. Education is a major impact factor for cognitive performance., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Culture is a dynamic system of bidirectional influences among individuals and their environment, including psychological and biological processes, which facilitate adaptation and social interaction. One of the main challenges in clinical neuropsychology involves cognitive, behavioral and functional assessment of people with different sociocultural backgrounds. In this review essay, examining culture from a historical perspective to ethical issues in cross-cultural research, including the latest significant and publications, the authors sought to explore the main features related to cultural variables in neuropsychological practice and to debate the challenges found regarding the operational methods currently in use. Literature findings suggest a more comprehensive approach in cognitive and behavioral neuroscience, including an interface between elementary disciplines and applied neuropsychology. Thus, as a basis for discussion on this issue, the authors analyzed key-topics related to the study of new trends in sociocultural neuroscience and the application of their concepts from a clinical perspective., Competing Interests: Disclosure: The authors report no conflits of interest.

Background: Neurocysticercosis is a parasitic disease that affects the central nervous system. Its main clinical manifestations are epileptic seizures. The objective of this study was to investigate the correlation between neurotransmitter concentrations in cerebrospinal fluid (CSF) and the different evolutive forms of neurocysticercosis with or without seizures., Methods: Neurotransmitter concentrations (Aspartate, Glutamate, GABA, Glutamine, Glycine, Taurine) were determined in CSF samples from 42 patients with neurocysticercosis divided into patients with the active cystic form (n = 24, 12 with and 12 without seizures) and patients with calcified form (n = 18, 12 with and 6 without seizures), and a control group consisting of 59 healthy subjects., Results: Alterations in amino acid concentration were observed in all patients with neurocysticercosis., Conclusion: We conclude that disturbances in amino acid metabolism accompany the presentation of neurocysticercosis. Replacement of the terms inactive cyst by reactive inactive cyst and calcification by reactive calcification is suggested.

Objectives: Naming deficit is a linguistic symptom that appears in the initial phase of Alzheimer's disease, but the types of naming errors and the ways in which this deficit changes over the course of the disease are unclear. We analyzed the performance of patients with Alzheimer's disease on naming tasks during the mild and moderate phases and verified how this linguistic skill deteriorates over the course of the disease., Methods: A reduced version of the Boston Naming Test was administered to 30 patients with mild Alzheimer's disease, 30 patients with moderate Alzheimer's disease and 30 healthy controls. Errors were classified as verbal semantic paraphasia, verbal phonemic paraphasia, no response (pure anomia), circumlocution, unrelated verbal paraphasia, visual errors or intrusion errors., Results: The patients with moderate Alzheimer's disease had significantly fewer correct answers than did both the control group and the group with mild Alzheimer's disease. With regard to the pattern of errors, verbal semantic paraphasia errors were the most frequent errors in all three groups. Additionally, as the disease severity increased, there was an increase in the number of no-response errors (pure anomia). The group with moderate Alzheimer's disease demonstrated a greater incidence of visual errors and unrelated verbal paraphasias compared with the other two groups and presented a more variable pattern of errors., Conclusions: Performance on nominative tasks worsened as the disease progressed in terms of both the quantity and the type of errors encountered. This result reflects impairment at different levels of linguistic processing.

Sleep length and architecture are potential markers of progressive cognitive impairment, while neuropsychiatric symptoms and APOE4- haplotypes have been associated with more sleep complaints in patients with dementia due to Alzheimer's disease (AD). In this cross-sectional study, we sought to investigate which factors might be related to sleep satisfaction in patients with AD. A total of 217 consecutive patients with AD were assessed for demographic features, neuropsychiatric symptoms, cognitive decline, functional impairment for activities of daily living, caregiver burden, APOE haplotypes, self-reported sleep satisfaction and length of sleep. Statistical comparisons were conducted with significance at p<0.05. Concerning sleep complaints, 179 patients (82.5%) reported satisfactory sleep, while 38 (17.5%) were unsatisfied, with no relation to age, sex, APOE haplotypes, obesity, education, marital status, alcohol consumption or smoking found. Length of sleep (p=0.011) and behavioural symptoms (p=0.009) had significant associations with sleep satisfaction. Length of sleep was positively correlated with apathy (p=0.014) and scores on the Clock Drawing Test (p=0.015), and inversely correlated with anxiety (p=0.015) and independence for instrumental activities of daily living (p=0.003). Patients who were treated with memantine (p=0.02) or anti-psychotics (p<0.01) had longer duration of sleep. In conclusion, behavioural symptoms had strong associations with sleep satisfaction, which is highly correlated with length of sleep in patients with AD. Functional independence, apathy, anxiety, use of memantine or anti-psychotics, and scores on the Clock Drawing Test were significantly associated with length of sleep in this sample., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Pharmacological treatment has mild effects for patients with Alzheimer's disease dementia (AD); therefore, the search for modifiable risk factors is an important challenge. Though risk factors for AD are widely recognized, elements that influence the time of dementia onset have not been comprehensively reported. We aimed to investigate which risk factors might be related to the age of onset of AD in a sample of patients with highly variable educational levels, taking into account the Framingham risk scoring as the sole measure of vascular risk., Subjects and Methods: We included 209 consecutive late-onset AD patients to find out which factors among educational levels, coronary heart disease risk estimated by way of Framingham risk scores, history of head trauma or depression, surgical procedures under general anesthesia, family history of neurodegenerative diseases, gender, marital status and APOE haplotypes might be related to the age of dementia onset in this sample of patients with low mean schooling., Results: Mean age of AD onset was 73.38±6.5 years old, unaffected by schooling or family history of neurodegenerative diseases. Patients who were APOE-ε4 carriers, married, or with history of depression, had earlier onset of AD, particularly when they were women. Coronary heart disease risk was marginally significant for later onset of AD., Conclusions: APOE haplotypes, marital status and history of depression were the most important factors to influence the age of AD onset in this sample. While midlife cerebrovascular risk factors may increase incidence of AD, they may lead to later dementia onset when present in late life.

Objective: In view of the mild effects of pharmacological treatment for dementia due to Alzheimer's disease (AD), the search for modifiable risk factors is an important challenge. Although risk factors for AD are widely recognized, elements that influence the time of onset of the dementia syndrome have not been comprehensively reported. We aimed to investigate which risk factors might be associated with the age at onset of AD in a sample of patients with low mean schooling from São Paulo, Brazil., Methods: We included 210 consecutive patients with late-onset AD to investigate whether education, gender, nationality, urban living and sanitation, occupation, cognitive and physical inactivity, head trauma, depression, systemic infections, surgical interventions, cerebrovascular risk factors, family history of neurodegenerative diseases or cardiovascular diseases and apolipoprotein E gene (APOE) haplotypes might be related to the age at AD onset., Results: Each copy of APOE-ε4 led to onset of AD almost 2 years earlier, while depression, smoking, higher body mass index and family history of cardiovascular diseases were also highly significant. Protective factors included non-Brazilian nationality, use of a pacemaker and waist circumference. Cerebrovascular risk factors had a mild combined effect for earlier onset of AD., Conclusion: APOE haplotypes, depression, nationality and cerebrovascular risk factors were the most important elements to influence the age at AD onset in this sample, whereas gender, education, occupation and physical activities had no isolated effects over the age at onset of this dementia syndrome., (Copyright © 2014 John Wiley & Sons, Ltd.)

Alzheimer's disease (AD) is characterized by impairments in memory and other cognitive functions such as language, which can be affected in all aspects including discourse. A picture description task is considered an effective way of obtaining a discourse sample whose key feature is the ability to retrieve appropriate lexical items. There is no consensus on findings showing that performance in content processing of spoken discourse deteriorates from the mildest phase of AD., Objective: To compare the quantity and quality of discourse among patients with mild to moderate AD and controls., Methods: A cross-sectional study was designed. Subjects aged 50 years and older of both sexes, with one year or more of education, were divided into three groups: control (CG), mild AD (ADG1) and moderate AD (ADG2). Participants were asked to describe the "cookie theft" picture. The total number of complete words spoken and information units (IU) were included in the analysis., Results: There was no significant difference among groups in terms of age, schooling and sex. For number of words spoken, the CG performed significantly better than both the ADG 1 and ADG2, but no difference between the two latter groups was found. CG produced almost twice as many information units as the ADG1 and more than double that of the ADG2. Moreover, ADG2 patients had worse performance on IUs compared to the ADG1., Conclusion: Decreased performance in quantity and content of discourse was evident in patients with AD from the mildest phase, but only content (IU) continued to worsen with disease progression., Competing Interests: Disclosure: The authors report no conflicts of interest.

Unlabelled: Cognitive assessment in advanced stages of Alzheimer's disease (AD) is limited by the imprecision of most instruments., Objective: To determine objective cognitive responses in moderate and severe AD patients by way of the Severe Mini-Mental State Examination (SMMSE), and to correlate performances with Mini-Mental State Examination (MMSE) scores., Method: Consecutive outpatients in moderate and severe stages of AD (Clinical Dementia Rating 2.0 or 3.0) were evaluated and compared according to MMSE and SMMSE scores., Results: Overall 400 patients were included, 67.5% females, mean age 76.6±6.7 years-old. There was no significant impact of age or gender over MMSE or SMMSE scores. Mean schooling was 4.4±2.5 years, impacting SMMSE scores (p=0.008). Scores on MMSE and SMMSE were significantly correlated (F-ratio=690.6325, p<0.0001)., Conclusion: The SMMSE is influenced by schooling, but not by age or gender, and is an accurate test for assessment of moderate and severe AD.

To evaluate correlations of pharmacological treatment with cognitive and behavioral symptoms in patients with dementia due to Alzheimer's disease with low schooling, subjects were assessed for demographic features, neuropsychiatric symptoms, cognitive decline, functionality, caregiver burden, APOE haplotypes and pharmacological treatment. Among 217 patients, use of cholinesterase inhibitors with or without Memantine was associated with less neuropsychiatric symptoms, while anti-psychotics and/or anti-epileptic drugs were associated with lower instrumental functionality. Anti-psychotics were also associated with more neuropsychiatric symptoms in moderately impaired patients, possibly reflecting the greater need for such treatment when behavioral symptoms are present. Patients receiving more medications were usually younger, obese, married, with higher schooling and more neuropsychiatric symptoms. APOE4+ haplotypes were correlated with earlier dementia onset, but not with pharmacological treatment. Higher caregiver burden was associated with more psychotropic drugs. A trend was found for treatment with cholinesterase inhibitors and Memantine to be associated with longer lengths of dementia for moderately impaired but not for severely impaired patients, regardless of APOE haplotypes, translating into a synergistic effect among such medications for slowing cognitive decline but not for prolonging survival. Further longitudinal studies may be required to assess dose-response relationships regarding treatment with psychotropics for patients with dementia., (© 2013.)

Controversy over benefits of angiotensin-converting enzyme inhibitors (ACEIs) for treatment of dementia due to Alzheimer's disease (AD) led to this alternative investigational approach by the employment of pharmacogenetic methods, correlating the cognitive change of patients with late-onset AD with the presence of common ACE gene promoter polymorphisms, and stratifying the sample in groups of patients who responded or not to the brain-penetrating ACEIs Captopril or Perindopril. A trend was found for treatment with brain-penetrating ACEIs to slow cognitive decline in AD patients with the haplotype rs1800764 (CC): rs4291 (TT) (p = 0.024), and also non-significantly for independent carriers of rs1800764 or rs4291.