Differential associations of clinical features with cerebrospinal fluid biomarkers in dementia with Lewy bodies and Alzheimer's disease.

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-ß (Aß42,Aß40,Aß38), tau, phospho-tau Thr181, 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, Aß42/Aß38 and Aß42 were lower, while tau/Aß42 and phospho-tau Thr181/Aß42 were higher; α-synuclein/Aß42 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 Thr181 and tau/Aß42, 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 Thr181/Aß42 and α-synuclein/Aß42, and Severe MMSE inversely associated with tau/Aß42 and tau/phospho-tau Thr181. CONCLUSIONS: Cerebrospinal fluid phospho-tau Thr181 in DLB was similar to AD, but not Aß42. In associations with test scores, biomarker ratios were superior to isolated biomarkers, while worse functionality was associated with axonal degeneration only in AD.

Pharmacogenetics of angiotensin modulators according to APOE-ϵ4 alleles and the ACE insertion/deletion polymorphism in Alzheimer's disease.

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-ß by suppressing effects of the angiotensin-converting enzyme 1, an amyloid-ß-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.

APOE ε4 Carrier Status as Mediator of Effects of Psychotropic Drugs on Clinical Changes in Patients With Alzheimer's Disease.

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.

Behavioural effects of the ACE insertion/deletion polymorphism in Alzheimer's disease depend upon stratification according to APOE-ϵ4 carrier status.

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.

Health care professionals and use of digital technologies in patients with dementia and related disorders.

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.

Evaluation of macrolinguistic aspects of the oral discourse in patients with Alzheimer's disease.

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.

Pharmacogenetic analyses of variations of measures of cardiovascular risk in Alzheimer's dementia.

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 ß 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.

Effects of APOE haplotypes and measures of cardiovascular risk over gender-dependent cognitive and functional changes in one year in Alzheimer's disease.

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 (ß = -0.091; p = 0.037) and MMSE (ß = 0.126; p = 0.017) scores, while increased creatinine clearance was associated with improvements in ADL (ß = 0.028; p = 0.012) and MMSE (ß = 0.043; p = 0.039) scores and higher schooling led to faster worsening of IADL (ß = -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.

Clinical variables related to the diagnostic stability of demential syndromes.

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.

Neurological impressions on the organization of language networks in the human brain.

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.

Associations of Blood Pressure with Functional and Cognitive Changes in Patients with Alzheimer's Disease.

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, ß-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.

Risk factors for age at onset of dementia due to Alzheimer's disease in a sample of patients with low mean schooling from São Paulo, Brazil.

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.

Assessment of risk factors for earlier onset of sporadic Alzheimer's disease dementia.

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.

Language impairments in Alzheimer´s disease: What changes can be found between mild and moderate stages of the disease?

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.

Speech and orofacial apraxias in Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) affects not only memory but also other cognitive functions, such as orientation, language, praxis, attention, visual perception, or executive function. Most studies on oral communication in AD focus on aphasia; however, speech and orofacial apraxias are also present in these patients. The aim of this study was to investigate the presence of speech and orofacial apraxias in patients with AD with the hypothesis that apraxia severity is strongly correlated with disease severity. METHODS: Ninety participants in different stages of AD (mild, moderate, and severe) underwent the following assessments: Clinical Dementia Rating, Mini-Mental State Examination, Lawton Instrumental Activities of Daily Living, a specific speech and orofacial praxis assessment, and the oral agility subtest of the Boston diagnostic aphasia examination. RESULTS: The mean age was 80.2 ± 7.2 years and 73% were women. Patients with AD had significantly lower scores than normal controls for speech praxis (mean difference=-2.9, 95% confidence interval (CI)=-3.3 to -2.4) and orofacial praxis (mean difference=-4.9, 95% CI=-5.4 to -4.3). Dementia severity was significantly associated with orofacial apraxia severity (moderate AD: ß =-19.63, p= 0.011; and severe AD: ß =-51.68, p < 0.001) and speech apraxia severity (moderate AD: ß = 7.07, p = 0.001; and severe AD: ß =8.16, p < 0.001). CONCLUSION: Speech and orofacial apraxias were evident in patients with AD and became more pronounced with disease progression.

Cognitive impairment in fibromyalgia.

Cognitive and behavioral impairments are core manifestations of fibromyalgia and may be more disabling than pain itself. Involvement of the central nervous system is ascertained by the fact that frontoparietal and limbic cortices are often functionally and structurally affected along the course of this disease. Even though neuroimaging has brought some experimental evidence to support such network disruption, there are currently no clinically effective biomarkers that detect and quantify cognitive and behavioral disturbances in fibromyalgia; thus, traditional scales and tests of neuropsychiatric assessment remain the most important diagnostic tools. This review addresses the most common cognitive and behavioral impairments in people with fibromyalgia, while explaining their pathophysiological basis and currently available therapeutic options.

The knowledge of memory aging questionnaire (KMAQ) in a Brazilian sample: a questionnaire for informants to recognize early signs of dementia.

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.

Até o presente momento, poucos países desenvolveram programas destinados a cuidadores e familiares de pacientes com demência, objetivando o aprimoramento de conhecimentos, habilidades e estratégias para lidar com os sintomas dos pacientes. Entretanto, antes de prestar esse suporte especial, faz-se importante identificar crenças e pensamentos compartilhados por informantes acerca da cognição em pessoas idosas. Os questionários são instrumentos que permitem obter essa informação, a exemplo do Questionário de Conhecimento de Memória e Envelhecimento (KMAQ, sigla em inglês), que foi elaborado para avaliar mudanças normais e patológicas no processo de envelhecimento. Objetivo: O objetivo deste estudo foi avaliar o conhecimento sobre cognição, envelhecimento e demência pela aplicação do KMAQ em pessoas que estão em contato com pessoas idosas com e sem comprometimento cognitivo. Métodos: Setenta e oito familiares e cuidadores de pacientes idosos foram divididos em dois grupos: grupo 1 ­ parentes de pacientes com demência (n1=48); e grupo 2 ­ parentes de pessoas sem comprometimento cognitivo (n2=30). Foi-lhes solicitado responder a questionários sobre demência, incluindo o KMAQ. Resultados: Quando analisadas as pontuações do questionário para os itens de mudanças normais no envelhecimento (g1: 0,53 vs. g2: 0,53, valor p: 0,99) não tivemos diferenças significativas no conhecimento entre os dois grupos, não havendo diferenças na pontuação para os itens de mudanças patológicas no envelhecimento (g1: 0,55 vs. g2: 0,55, valor p: 0,969). Conclusões: Estar em contato com a demência não parece melhorar o conhecimento sobre essa síndrome. Conhecer as mudanças normais na cognição durante o envelhecimento permite identificar "sinais de alarme" sugestivos de processos degenerativos, alcançando-se um diagnóstico precoce e mais opções para o tratamento.

Speech and phonological impairment across Alzheimer's disease severity.

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.

Pharmacogenetic Analyses of Therapeutic Effects of Lipophilic Statins on Cognitive and Functional Changes in Alzheimer's Disease.

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.

Treatment of dementia: recommendations of the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology.

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.

Atualmente não há tratamento curativo para as demências neurodegenerativas ou para a demência vascular, mas algumas intervenções farmacológicas e não farmacológicas podem contribuir para aliviar os sintomas, retardar a progressão da doença e melhorar a qualidade de vida. As abordagens terapêuticas atuais são baseadas na etiologia, no perfil dos sintomas e no estágio da demência. Neste artigo apresentamos recomendações sobre os tratamentos farmacológicos e não farmacológicos da demência devida à doença de Alzheimer, comprometimento cognitivo vascular, demência frontotemporal, demência da doença de Parkinson e demência com corpos de Lewy.