Factors associated with dementia in elderly

Abstract

We analyzed the factors associated with dementia in the elderly attended at a memory outpatient clinic of the University of Southern Santa Catarina (UNISUL). This is a cross-sectional study with data analysis of medical records from January 2013 to April 2016. The outcome was the clinical diagnosis of dementia. The control variables were: serum vitamin D level at the time of diagnosis, gender, skin color, schooling, age, type 2 diabetes, hypertension, and depression. We performed a crude and adjusted analysis with logistic regression. The sample consisted of 287 elderly, with the predominance of age between 60 and 69 years (48.78%), female (79.09%) and white (92.33%). The mean number of years of study was 6.95 years (SD ± 4.95) and mean vitamin D was 26.09 ng/mL (SD ± 9,20). The prevalence of elderly with dementia was 16.72%. Depression was the most prevalent (42.50%) among the morbidities, followed by hypertension (31.71%). The following were independently associated with dementia: vitamin D (OR = 0.92, 95%CI, 0.88;0.97), depression (OR = 4.09, 95%CI, 1.87;8.94), hypertension (OR = 2.65, 95%CI, 1.15;6.08) and individuals aged 80 years and over (OR = 3.97 95%CI, 1.59;9.91). Dementia prevalence was high and diagnosed dementia was associated with lower levels of vitamin D. Vitamin D is a modifiable factor, opening up essential perspectives for public health policies.

Key words
Elderly; Dementia; Memory outpatient clinic

Resumo

Analisar os fatores associados à demência em idosos atendidos em um ambulatório de memória da Universidade do Sul de Santa Catarina (Unisul). Estudo transversal com análise de dados de prontuário no período de 01/2013 a 04/2016. O desfecho foi o diagnóstico clínico de demência. As variáveis de controle foram: nível sérico de vitamina D na época do diagnóstico, sexo, cor da pele, escolaridade, idade, diabetes tipo 2, hipertensão arterial e depressão. Foi realizada análise bruta e ajustada com regressão logística. Amostra de 287 idosos, com predominância de idade entre 60 e 69 anos (48,78%), sexo feminino (79,09%), cor da pele branca (92,33%). A média de anos de estudo foi de 6,95 anos (DP ± 4,95) e da vitamina D 26,09 ng/mL (DP ± 9,20). A prevalência de idosos com demência foi de 16,72%. Dentre as morbidades a depressão foi a de maior prevalência seguida pela hipertensão arterial. Estiveram independentemente associadas à demência: vitamina D (OR = 0,92 IC 95% 0,88;0,97), depressão (OR = 4,09 IC95% 1,87;8,94), hipertensão arterial (OR = 2,65 IC95% 1,15;6,08) e indivíduos com idade igual e maior que 80 anos. A prevalência de demência foi alta, e houve associação de níveis mais baixos de vitamina D com diagnóstico de demência. Sendo a vitamina D um fator modificável, abrindo importantes perspectivas para políticas de saúde pública.

Palavras-chave
Idoso; Demência; Ambulatório da memória

Introduction

The Brazilian’s population aging is accelerating. The population aged 60 years and over, equivalent to 10% of the total population in 2010, is estimated to reach 13.7% of the population by 2020 and 23.8% by 2040, or almost a quarter of nationals will consist of elderly¹. These transformations in the age pyramid result from the changes in the balance between birth and mortality, as well as in the morbidity profile of the population, characterizing the demographic and epidemiological transition.

With increased life expectancy, chronic noncommunicable diseases (DCNT) stand out as a significant public health challenge, mainly due to the high morbidity they cause. These diseases can result in severe degrees of disability that affect both the life and well-being of the individuals and the country’s economy. In 2002, CNCDs accounted for almost 60% of all deaths². Approximately 80% of the elderly have at least one chronic disease, of which 50% with two or more pathologies³.

Among the aging-related CNCDs are dementias, which stand out as the leading causes of functional impairment and the quality of life of the elderly⁴. According to the World Health Organization (WHO) in 2012, more than 35 million people in the world had some level of dementia, which can triple by 2050 to more than 115 million people, and the highest prevalence of dementia will fall on low- and middle-income countries, with about 60% of dementia cases⁵.

According to WHO⁶, the time lived with dementia accounts for 11.9% of the years of living with disabilities due to noncommunicable diseases, with an estimated global cost of US$ 604 billion in 2010.

Cognitive losses due to dementia are more prevalent in females⁷, among low schooling individuals⁸ who do not engage in physical activity⁹, people with low economic status¹⁰, advanced age¹¹ and frailty¹². Other risk factors associated with dementia are hypertension¹³, diabetes mellitus¹⁴, depression¹⁵ and low levels of vitamin D¹⁶, and the latter is a modifiable factor.

In recent years, associations between vitamin D and dementia have attracted increasing interest^16,17. Studies indicate that vitamin D deficiency is more prevalent in patients with dementia¹⁸. A meta-analysis has shown that demented individuals have a lower level of vitamin D (25-hydroxyvitamin D (25 (OH) D)) compared with the control group healthy age-matched patients¹⁹. Lower 25 (OH) D may be only a marker or potential risk factor for developing dementia, as indicated by recent studies^18-21.

In the study by Baumgart et al.²², the importance of studies aimed at analyzing modifiable risk factors for dementia is emphasized, since these are amenable to intervention, highlighting the practice of healthy behaviors.

Thus, this study aims to analyze the factors associated with dementia in the elderly followed by a Memory Outpatient Clinic of the University of Southern Santa Catarina.

Methods

This is a cross-sectional study conducted in the city of Palhoça, Santa Catarina. According to IBGE²³, the city of Palhoça consists of approximately 137,334 inhabitants. Of these, individuals aged 60 and over correspond to 30,513 inhabitants (8.79%). Data were analyzed from the records of the elderly monitored by the Memory Outpatient Clinic of the University of Southern Santa Catarina (Unisul).

A total of 406 medical records were identified from January 2013 to April 2016, of which 119 were excluded since the medical records did not show the serum vitamin D dose. The final sample of the study consisted of 287 elderly. Inclusion criteria were individuals aged 60 years and over, with a clinical diagnosis of the cognitive status and who had serum 25-hydroxyvitamin D 25 (OH) D at the time of diagnosis as part of standardized routine tests for the investigation of dementia and its causes. Exclusion criteria were individuals who had recently taken or were taking vitamin D replacement during the study period, patients with delirium or other acute diseases at the time of collection of the tests or the diagnostic process for dementia.

Regarding the dependent variable, dementia was analyzed from the clinical diagnosis, which was composed of anamnesis, physical and neurological examination, complementary exams and cognitive evaluation^24,25. The cognitive evaluation tests for screening and diagnostic support used were the Montreal Cognitive Assessment (MoCA) and the Clinical Dementia Rating (CDR), both validated for Brazil.

The independent variables were serum levels of vitamin D (25 (OH) D) in ng/mL, age (60-69, 70-79 and 80 years and over), gender (male and female), skin color (white, black and brown), schooling (full study years), and concerning health conditions (diabetes mellitus, hypertension and depression), data were obtained from the clinical diagnosis and were dichotomized in "no" and "yes".

Statistical analysis was performed using the Stata/SE 13.0 program. The descriptive statistics with absolute and relative frequency were performed by calculating the measures of central tendency and dispersion for the continuous variables, and of frequency for the categorical variables. Concerning the identification of the dementia-associated factors, bivariate analyzes were initially performed between each exposure variable and the dependent variable, and Pearson’s chi-square test (χ²) was used, with a significance level of 5%. Odds ratios (unadjusted OR) were also obtained between dichotomous variables and their respective 95% confidence intervals (95% CI).

Multivariate logistic regression was performed using all variables of bivariate analysis to identify variables that remained significantly related to the occurrence of dementia (p < 0.05) and with biological plausibility. The maximum likelihood ratio test was used to verify the significance of the final model.

The Human Research Ethics Committee (CEPSH) of the Federal University of Santa Catarina (UFSC) approved this study, with co-participation of the University of Southern Santa Catarina. All participants – and in case of vulnerability, the legal guardian – signed an informed consent form.

Results

The sample consisted of 287 older adults, aged 60-69 years (48.78%), female (79.09%) and white (92.33%). The prevalence of elderly with dementia was 16.72%. Among the elderly with dementia, the mean vitamin D levels were 21.90 (SD ± 8.10), and elderly without dementia averaged 26.93 ng/mL (SD ± 8.80).

Among morbidities, depression was the most prevalent (42.50%), followed by hypertension (31.71%) and diabetes mellitus (20.21%). The mean number of study years was 6.95 (SD ± 4.95) and mean vitamin D was 26.09 ng/mL (SD ± 9,20) (Table 1).

Table 1
Description of the sample of elderly participants of the Memory Outpatient Clinic (UNISUL), Palhoça (SC), Brazil, 2013-2016 (n = 287).

Variables	n (%) Mean (SD*)
Dementia
No	239 (83.28)
Yes	48 (16.72)
Gender
Male	60 (20.91)
Female	227 (79.09)
Age (years)
60-69	140 (48.78)
70-79	101 (35.19)
80+	46 (16.03)
Skin color
White	265 (92.33)
Non-White	22 (7.67)
Depression
No	165 (57.49)
Yes	122 (42.51)
Hypertension
No	196 (68.29)
Yes	91 (31.71)
Diabetes
No	229 (79.79)
Yes	58 (20.21)
Vitamin D	26.09 ( ± 9.20)
Schooling	6.95 ( ± 4.95)

• ^*
  SD (Standard Deviation).

In the bivariate analysis, increased vitamin D had a protective effect vis-à-vis dementia (OR = 0.93, 95%CI 0.89;0.97); concerning morbidities, the elderly diagnosed with depression were 166% more likely to have the outcome (OR = 2.66 95%CI 1.40;5.05). Subjects aged 80 years and over were 354% more likely to have dementia compared to those aged 60-69 years (OR = 4.54 95%CI 2.05;10.04) (Table 2).

Table 2
Crude and adjusted analysis of variables associated with dementia in elderly participants of the Memory Outpatient Clinic (UNISUL), Palhoça (SC), Brazil, 2013-2016.

Variables		Crude Analysis		Adjusted Analysis
	%	OR (CI95%)*	p-value	OR (CI95%)*	p-value
Vitamin D		0.93(0.89;0.97)	0.001	0.92(0.88;0.97)	0.001
Gender
Male	20.00	1.00		1.00
Female	15.85	0.75(0.36;1.55)	0.446	0.42(0.17;1.02)	0.060
Age (years)
60-69	11.43	1.00		1.00
70-79	14.85	1.35(0.63;2.88)	0.435	1.61(0.72;3.62)	0.247
80+	36.95	4.54(2.05;10.04)	<0.001	3.97(1.59;9.91)	0.003
Skin color
White	17.35	1.00		1.00
Black/Brown	9.10	0.47(0.11;2.10)	0.318	0.54(0.11;2.58)	0.439
Schooling		0.95(0.88;1.02)	0.138	0.95(0.88;1.03)	0.260
Depression
No	10.90	1.00		1.00
Yes	24.60	2.66(1.40;5.05)	0.003	4.09(1.87;8.94)	0.001
Hypertension
No	15.81	1.00		1.00
Yes	18.68	1.22(0.64;2.34)	0.545	2.68(1.16;6.18)	0.020
Diabetes
No	14.85	1.00		1.00
Yes	24.14	1.82(0.90;3.68)	0.090	2.12(0.91;4.95)	0.080

• Obs.: Pearson's (p = 0.39)
• ^*
  Crude OR: odds ratio; CI95%: 95% Confidence Interval.

In the adjusted analysis, vitamin D remained independently associated with dementia – each unit of vitamin D (ng/mL) reduces by 8% the probability of the outcome (OR = 0.92, 95%CI 0.88;0.97) –; elderly patients diagnosed with depression (OR = 4.09, 95%CI 1.87, 8.94) and hypertension (OR = 2.68 95%CI 1.15;6.08) were more likely to have dementia (309%, and 168%, respectively) when compared with elderly without the disease. Regarding age, older individuals aged 80 years and over were 297% more likely to be diagnosed with dementia when compared to those aged 60-69 years (OR = 3.97, 95% CI 1.59;9.91) (Table 2). The final model was considered adjusted (p = 0.39) from the maximum likelihood ratio test.

Discussion

At the time of this review, this was the first Brazilian study that evaluated the factors associated with dementia in the elderly in a memory outpatient setting. The prevalence of dementia found in this study was 16.72%, higher than that of Nitrini et al. who evaluated studies on the prevalence of dementia in Latin American countries and found a prevalence of 7.1%. This difference was due to the specificity of a population attended at a memory outpatient clinic that receives people with suspected cognitive problems²⁶ referred from primary care.

In Brazil, few studies evaluate dementia in the elderly population, and the existing ones show significant differences concerning prevalence and incidence. In a recent systematic review²⁷, the prevalence of dementia among Brazilian elderly ranged from 5.1% to 19%, but most studies evaluated the cognitive status by questionnaires such as the Mini-Mental State Examination (MMSE), and not from the diagnosis (gold standard) as in this study.

We found that the prevalence of having a diagnosis of dementia fell 8% with each vitamin D (ng/mL) unit increase, and recent studies have shown these associations^16,17,20,21. In a cohort study with French elderly monitored for 12 years, elderly patients with insufficient vitamin D (< 20 ng/mL) and vitamin D deficiency (< 20 ng/mL) were approximately three times more likely to have dementia²⁸.

The results of this study corroborate other experimental studies that suggested that hypovitaminosis D could mediate the neurodegenerative processes involved in dementias^16,29,30. Case-control studies indicated that individuals with dementia had lower circulating levels of vitamin D^31,32. Also, several longitudinal studies found an association between low vitamin D levels and accelerated cognitive decline^30,33-36.

However, there are conflicting results, such as those found in two longitudinal studies conducted in Sweden and the United States. No association was found between vitamin D levels and the cognitive status of the elderly in these studies. However, in the study carried out in Sweden³⁷, the sample consisted only of men and the prevalence of hypovitaminosis D was low; of these, 15.5% had insufficiency and 1.7% deficiency. In the U.S. study³⁸, while no associations were found between vitamin D and dementia, low vitamin D concentrations were found to be associated with worse executive function, processing speed and visual and perceptive abilities.

It is known that vitamin D plays a vital role in brain development and maturation of vitamin D receptors (VDRs) present in various areas of the brain, including those related to learning and memory functions. Besides, vitamin D is involved in several brain health pathways, including neurotransmission, neuroprotection, modulation of immune response, inhibition of pro-inflammatory agents and regulation of oxidative stress^16,30,39.

Studies were conducted to verify the effect of vitamin D supplementation on cognitive function. However, Annweiler et al.⁴⁰ observed that an improved cognitive function was found after the addition of 800 IU/day of vitamin D in elderly with cognitive decline. The daily consumption of 800 IU of vitamin D resulted in lower Alzheimer’s risk after seven years of follow-up⁴¹. This neuroprotective effect was further confirmed by an experimental study that reported cognitive improvement⁴². The benefits of supplementation were noticeable after four weeks⁴³ and appeared to be particularly strong for executive function and processing speed⁴⁴.

Regarding morbidities, approximately 50% of the elderly of the sample had a diagnosis of depression. Barcelos-Ferreira et al.⁴⁵ reviewed the scientific literature on depression in community elderly in Brazil and identified a prevalence of 7% for depression and 26% for depressive symptoms. A study conducted with community elderly in Canada found a prevalence of depression ranging between 1.3% and 18.8% in women and between 0.9% and 7.9% in men⁴⁶.

Depressive elderly were 4.09 times more likely to have dementia. A recent 14-year longitudinal study showed that depressive male elders were more likely to have dementia (OR = 1.5 95%CI 1.2;2.0)⁴⁷. Norton et al. estimated that 5-11% of Alzheimer’s disease cases could be attributed to depression, and this means that the prevalence of dementia in the population would be reduced by the same amount if depression can be prevented or adequately treated⁴⁸.

On the other hand, in a study conducted by Mirza et al. In 2014, 4.393 elderly people were followed for up to 13.7 years for incident dementia and found that about 13% developed dementia and that depression increased the risk of dementia by approximately 20% for 2 and 5 years, but the same study suggests that depressive symptoms at advanced ages are part of the initial symptoms of dementia and not an independent risk factor for depression⁴⁹. There is evidence that depression can lead to loss of volume of the hippocampus, mainly when symptoms are persistent, thus contributing to the onset of dementia⁵⁰.

Concerning hypertension, after the adjusted analysis, the elderly with hypertension were 168% more likely to have dementia, corroborating a study conducted in people over 80 years in China, which found that the hypertensive elderly were 193% more likely to evidence mild cognitive disorder and evolve towards dementia⁵¹.

Interestingly, in people 60 years of age or older, systolic blood pressure (SBP) was inversely associated with all-cause dementia⁵². This is paradoxical because it is generally recognized as a risk factor for cognitive decline and dementia^53-55. However, the association between blood pressure and the brain is complex and depends on factors such as age, chronicity, and use of antihypertensive medication⁵².

Antihypertensive therapies may reduce cognitive decline and the incidence of dementia. Most observational studies have suggested a potential preventive effect of antihypertensive therapies on cognitive decline and dementia, particularly calcium channel blockers and renin-angiotensin system blockers⁵⁶.

No association was found between diabetes mellitus and dementia in this study, possibly because of the sample size. However, in a meta-analysis, the relative risk of dementia in patients with diabetes was estimated at 1.46. Based on six studies gathering a total of 5,706 people with diabetes and 36,191 without diabetes, the analyzed relative risk for vascular dementia was 2.48, i.e., there was a considerably increased risk for this type of dementia⁵⁷.

The prevalence of women in the study was 79.09%, and this is associated with feminization in old age, women represent 55.5% of the Brazilian elderly population and 61% of the elderly population over 80 years of age²³. This female overrepresentation results from the longer life expectancy of women who, on average, live eight years longer than men⁵⁸.

The age group 80 years and older were 297% more likely to have dementia when compared to the 60-69 age group. Several studies^26,27,59 have shown this relationship in which older individuals are more likely to have dementia. Regarding the gender variable, there was no association with the outcome, but many studies^26,27 indicate that female subjects are more likely to have the outcome.

Dementia has a significant impact on the costs of society and the family. When investigating 41 households of dementia carriers residing in Rio de Janeiro, Veras et al. (2008) found that the projection of costs associated with the care of elderly with dementia reached approximately of two-thirds of the household income, with a 75% increase when the elderly were in the early stages of the disease and 80% when other chronic diseases were considered⁶⁰.

In 1998, Meek et al. stated that concerning total costs to society, dementia was the third most expensive disease in the U.S., after cancer and coronary heart disease⁶¹. Also, Brookmeyer et al.⁶² mentioned that the impact of healthcare-related costs for the treatment of dementia would be huge, burdening the U.S. economy with up to US$ 36 billion per year.

Recent estimates have shown that the costs associated with dementia in the UK top 17 billion euros per year, which are estimated to reach 50 billion euros by 2038, with an incidence of 1.4 million new cases per year⁶³. Dementia care social cost spirals dramatically with disease’s severity, and institutionalization is the main reason⁶⁴.

Limitations of this study were the lack of control regarding which season of the year vitamin D dosage tests were performed, assuming that there was a random distribution throughout the studied period. Because it is a cross-sectional study, it is not possible to infer causality. The population studied does not allow generalization of the results for the population as a whole, since it is a specialized outpatient clinic.

Conclusion

Dementias have a multifactorial origin and are a public health problem with high impact on health expenditure. In this study, dementia-associated factors were vitamin D, depression, hypertension, and age above 80 years. Knowing and understanding these factors assists in the medical clinic, diagnosis, and treatment of demented elderly.

The results of this study may positively influence public health policies where virtually costless lifestyle changes such as increased sun exposure may result in better health conditions for the elderly, both for possible protection against dementia and prevention of hypovitaminosis D among dementia carriers, avoiding major health problems. Further prospective, randomized and intervention studies with larger samples will ensure continuity of this work.

Referências

• ¹
  Mendes ACD, Sá DA, Miranda GMD, Lyra TM, Tavares RAW. Assistência pública de saúde no contexto da transição demográfica brasileira: exigências atuais e futuras. Cad Saude Publica 2012; 28(5):955-964.
• ²
  Monteiro CA, Moura EC, Jaime PC, Lucca A, Florindo AA, Figueiredo ICR, Bernal R, Silva NN. Monitoramento de fatores de risco para doenças crônicas por meio de entrevistas telefônicas: métodos e resultados no município de São Paulo. Rev Saude Publica 2005; 39(1):47-57.
• ³
  Hakansson K, Rovio S, Helkala EL, Vilska AR, Winblad B, Soininen H, Nissinen A, Mohammed AH, Kivipelto M. Association between mid-life marital status and cognitive function in later life: population based cohort study. BMJ 2009; 339:b2462
• ⁴
  Ballard C, Gauthier S, Corbett A, Brayne C, Aarsland D, Jones E. Alzheimer’s disease. Lancet 2011; 377(9770):1019-1031.
• ⁵
  World Health Organization (WHO). Dementia: a public health priority Geneva: WHO; 2012.
• ⁶
  World Health Organization (WHO). The global burden of disease: 2004 update Geneva: WHO ; 2008.
• ⁷
  Santos AA, Mansano-Schlosser TCS, Ceolim MF, Pavarini SCI. Sono, fragilidade e cognição:estudo multicêntrico com idosos brasileiros. Rev Bras Enferm 2013; 66(3):351-357.
• ⁸
  Trindade APNT, Barboza MA, Oliveira FB, Borges APO. Repercussão do declínio cognitiva na capacidade funcional em idosos institucionalizados e não institucionalizados. Fisioter Mov 2013; 26(2):281-289.
• ⁹
  Freitas DHM, Campos FCA, Linhares LQ, Santos CR, Ferreira CB, Diniz BS, Tavares A. Autopercepção da saúde e desempenho cognitivo em idosos residentes na comunidade. Rev Psiquiatr Clín 2010; 37(1):32-35.
• ¹⁰
  Macêdo AML, Cerchiari EAN, Alvarenga MRM, Faccenda O, Oliveira MAC. Avaliação funcional de idosos com déficit cognitivo. Acta Paul Enferm 2012; 25(3):358-363.
• ¹¹
  Castro-Costa E, Dewey ME, Uchôa E, Firmo JO, Lima-Costa MF, Stewart R. Trajectories of cognitive decline over 10 years in a Brazilian elderly population: the Bambuí cohort study of aging. Cad Saude Publica 2011; 27(Supl. 3):345-350.
• ¹²
  Faria EC, Silva SA, Farias KRA, Cintra A. Avaliação cognitiva de pessoas idosas cadastradas na estratégia saúde da família: município do Sul de Minas. Rev Esc Enferm USP 2011; 45(2):1748-1752.
• ¹³
  Banhato EFC, Guedes DV. Cognição e hipertensão: influência da escolaridade. Estud Psicol 2011; 28(2):143-151.
• ¹⁴
  Almeida-Pititto B, Almada Filho CM, Cendoroglo MS. Déficit cognitivo: mais uma complicação do diabetes melito? Arq Bras Endocrinol Metab 2008; 52(7):1076-1083.
• ¹⁵
  Trentini CM, Werlang BSG, Xavier FMF, Argimon IIL. A relação entre variáveis de saúde mental e cognição em idosos viúvos. Psicol Reflex Crít 2009; 22(2):236-243.
• ¹⁶
  Gezen-Ak D, Yılmazer S, Dursun E. Why vitamin D in Alzheimer’s disease? The hypothesis. J Alzheimers Dis 2014; 40(2):257-269.
• ¹⁷
  Morley JE. Dementia: does vitamin D modulate cognition? Nat Rev Neurol 2014; 10(11):613-614.
• ¹⁸
  Evatt ML, DeLong MR, Khazai N, Rosen A, Triche S, Tangpricha V. Prevalence of vitamin D insufficiency in patients with Parkinson disease and Alzheimer disease. Arch Neurol 2008; 65(10):1348-1352.
• ¹⁹
  Zhao Y, Sun Y, Ji HF, Shen L. Vitamin D levels in Alzheimer’s and Parkinson’s diseases: a meta-analysis. Nutrition 2013; 29(6):828-832.
• ²⁰
  Littlejohns TJ, Henley WE, Lang IA, Annweiler C, Beauchet O, Chaves PH, Fried L, Kestenbaum BR, Kuller LH, Langa KM, Lopez OL, Kos K, Soni M, Llewellyn DJ. Vitamin D and the risk of dementia and Alzheimer disease. Neurology 2014; 83(10):920-928.
• ²¹
  Afzal S, Bojesen SE, Nordestgaard BG. Reduced 25-hydroxyvitamin D and risk of Alzheimer’s disease and vascular dementia. Alzheimers Dement 2014; 10(3):296-302.
• ²²
  Baumgart M, Snyder HM, Carrillo MC, Fazio S, Kim H, Johns H. Summary of the evidence on modifiable risk factors for cognitive decline and dementia: A population-based perspective. Alzheimer’s & Dementia 2015; 11(6):718-726.
• ²³
  Instituto Brasileiro de Geografia e Estatística (IBGE). Estimativas populacionais enviadas para o TCU, estratificadas por idade e sexo pelo MS/SGEP/Datasus Rio de Janeiro: IBGE; 2012.
• ²⁴
  Parmera JB, Nitrini R. Investigation and diagnostic evaluation of a patient with dementia. Rev Med 2015; 94(3):179-184.
• ²⁵
  Nitrini R, Caramelli P, Bottino CMC, Damasceno BP, Brucki SMD, Anghinah R. Diagnóstico de Doença de Alzheimer no Brasil. Critérios diagnósticos e exames complementares. Arq Neuropsiquiatr 2005; 63(3):713-719.
• ²⁶
  Nitrini R, Bottino CM, Albala C, Custodio Capuñay NS, Ketzoian C, Llibre Rodriguez JJ, Maestre GE, Ramos-Cerqueira AT, Caramelli P. Prevalence of dementia in Latin America: a collaborative study of population-based cohorts. Int Psychogeriatr 2009; 21(4) :622-630.
• ²⁷
  Fagundes SD, Silva MT, Theer MFRS, et al. Prevalence of dementia among elderly Brazilians: a systematic review. Sao Paulo Med J 2011; 129(1):46-50.
• ²⁸
  Feart C, Helmer C, Merle B, Pereira MG. Associations of lower vitamin D concentrations with cognitive decline and long-term risk of dementia and Alzheimer’s disease in older adults. Alzheimer’s & Dementia 2017; 129(1):46-50.
• ²⁹
  Annweiler C, Bartha R, Goncalves S, Karras SN3, Millet P4, Féron F4, Beauchet O. Vitamin D-related changes in intracranial volume in older adults:A quantitative neuroimaging study. Maturitas 2015; 80(3):312-317.
• ³⁰
  Landel V, Annweiler C, Millet P, Morello M, Féron F. Vitamin D. Cognition and Alzheimer’s disease: the therapeutic benefit is in the D-Tails. J Alzheimers Dis 2016; 53(2):419-444.
• ³¹
  Annweiler C, Llewellyn DJ, Beauchet O. Low serum vitamin D concentrations in Alzheimer’s disease: a systematic review and meta-analysis. J Alzheimers Dis 2013; 33(3):659-674.
• ³²
  Balion C, Griffith LE, Strifler L, Henderson M, Patterson C, Heckman G, Llewellyn DJ, Raina P. Vitamin D, cognition, and dementia: a systematic review and meta-analysis. Neurology 2012; 79(13):1397-1405.
• ³³
  Miller JW, Harvey DJ, Beckett LA, Green R, Farias ST, Reed BR, Olichney JM, Mungas DM, DeCarli C. Vitamin D status and rates of cognitive decline in a multiethnic cohort of older adults. JAMA Neurol 2015; 72(11):1295-1303.
• ³⁴
  Moon JH, Lim S, Han JW, Kim KM, Choi SH, Kim KW, Jang HC. Serum 25-hydroxyvitamin D level and the risk of mild cognitive impairment and dementia: the Korean Longitudinal Study on Health and Aging (KLoSHA). Clin Endocrinol (Oxf) 2015; 83(1):36-42.
• ³⁵
  Annweiler C, Montero-Odasso M, Llewellyn DJ, Richard-Devantoy S, Duque G, Beauchet O. Meta-analysis of memory and executive dysfunctions in relation to vitamin D. J Alzheimers Dis 2013; 37(1):147-171.
• ³⁶
  Overman MJ, Pendleton N, O’Neill TW, Bartfai G, Casanueva FF, Finn JD, Forti G, Rastrelli G, Giwercman A, Han TS, Huhtaniemi IT, Kula K, Lean MEJ, Punab M, Lee DM, Correa ES, Ahern T, Verschueren SMP, Antonio L, Gielen E, Rutter MK, Vanderschueren D, Wu FCW, Tournoy J; EMAS Study Group. Evaluation of cognitive subdomains, 25- hydroxyvitamin D, and 1,25-dihydroxyvitamin D in the European Male Ageing Study. Eur J Nutr 2016; 56(6):2093-2103.
• ³⁷
  Olsson E, Byberg L, Karlstrom B, Cederholm T, Melhus H, Sjögren P, Kilander L. Vitamin D is not associated with incident dementia or cognitive impairment: an 18-y follow-up study in community-living old men. Am J Clin Nutr 2017; 105(4):936-943.
• ³⁸
  Karakis I, Pase MP, Beiser A, Booth SL, Jacques PF, Rogers G, DeCarli C, Vasan RS, Wang TJ, Himali JJ3, Annweiler C, Seshadri S. Association of serum vitamin D with the risk of incident dementia and subclinical indices of brain aging: The Framingham Heart Study. J Alzheimers Dis 2016; 51(2):451-461.
• ³⁹
  Brouwer-Brolsma EM, de Groot LC. Vitamin D and cognition in older adults: an update of recent findings. Curr Opin Clin Nutr Metab Care 2015; 18:11-16.
• ⁴⁰
  Annweiler C, Fantino B, Gautier J, Beaudenon M, Thiery S, Beauchet O. Cognitive effects of vitamin D supplementationin older outpatients visiting a memory clinic: a pre-post study. J Am Geriatr Soc 2012; 60(4):793-795.
• ⁴¹
  Annweiler C, Rolland Y, Schott AM, Blain H, Vellas B, Herrmann FR, Beauchet O. Higher vitamin D dietary intake is associated with lower risk of Alzheimer’s disease: a 7-year follow-up. J Gerontol A Biol Sci Med Sci 2012; 67(11):1205-1211.
• ⁴²
  Stein MS, Scherer SC, Ladd KS, Harrison LC. A randomized controlled trial of high-dose vitamin D2 followed by intranasal insulin in Alzheimer’s disease. J Alzheimers Dis 2011; 26(3):477-484.
• ⁴³
  Prybelski R, Agrawal S, Krueger D, Engelke JA, Walbrun F, Binkley N. Rapid correction of low vitamin D status in nursing home residents. Osteoporos Int 2008; 19(11):1621-1628.
• ⁴⁴
  Assmann KE, Touvier M, Andreeva VA, Deschasaux M, Constans T, Hercberg S, Galan P, Kesse-Guyot E. Midlife plasma vitamin D concentrations and performance in different cognitive domains assessed 13 years later. Br J Nutr 2015; 113(10):1628-1637.
• ⁴⁵
  Barcelos-Ferreira R, Izbicki R, Steffens DC, Bottino CM. Depressive morbidity and gender in community-dwelling Brazilian elderly: systematic reviewand meta-analysis. Int Psychogeriatr 2010; 22(5):712-726.
• ⁴⁶
  Ostbye T, Kristjansson B, Hill G, Newman SC, Brouwer RN, McDowell I. Prevalence and predictors of depression in elderly Canadians: the canadian study of health and aging. Chronic Dis Can 2005; 26(4):93-99.
• ⁴⁷
  Almeida OP, Hankey GJ, Yeap BB, Golledge J, Flicker L. Depression as a modifiable factor to decrease the risk of Dementia. Transl Psychiatry 2017; 7(5):e1117.
• ⁴⁸
  Norton S, Matthews FE, Barnes DE, Yaffe K, Brayne C. Potential for primary prevention of Alzheimer’s disease: an analysis of population-based data. Lancet Neurol 2014; 13(8):788-794.
• ⁴⁹
  Mirza SS, de Bruijn RF, Direk N, Hofman A, Koudstaal PJ, Ikram MA, Tiemeier H. Depressive symptoms predict incident dementia during short- but not long-term followup period. Alzheimers Dement 2014; 10:S323-S329.e321.
• ⁵⁰
  Taylor WD, McQuoid DR, Payne ME, Zannas AS, MacFall JR, Steffens DC. Hippocampus atrophy and the longitudinal course of late-life depression. Am J Geriatr Psychiatry 2014; 22(12):1504-1512.
• ⁵¹
  Hai S, Dong B, Liu Y, Zou Y. Occurrence and risk factors of MCI in the older. Int J Geriatr Psychiatry 2012; 27(7):703-708.
• ⁵²
  Gabin JM, Tambs K, Saltvedt I, Sund E, Holmen J. Association between blood pressure and Alzheimer disease measured up to 27 years prior to diagnosis: the HUNT Study. Alzheimer’s Research & Therapy 2017; 9:37
• ⁵³
  Kivipelto M, Helkala EL, Laakso MP, Hänninen T, Hallikainen M, Alhainen K, Soininen H, Tuomilehto J, Nissinen A. Midlife vascular risk factors and Alzheimer’s disease in later life: longitudinal, population based study. BMJ 2001; 322(7300):1447-1451.
• ⁵⁴
  Launer LJ, Ross GW, Petrovitch H, Masaki K, Foley D, White LR, Havlik RJ. Midlife blood pressure and dementia: the Honolulu-Asia aging study. Neurobiol Aging 2000; 21(1):49-55.
• ⁵⁵
  Skoog I, Lernfelt B, Landahl S, Palmertz B, Andreasson LA, Nilsson L, Persson G, Odén A, Svanborg A. 15-year longitudinal study of blood pressure and dementia. Lancet 1996; 347(9009):1141-1145.
• ⁵⁶
  Hernandorena I, Duron E, Vidal JS, Hanon O. Treatment options and considerations for hypertensive patients to prevent dementia. Expert Opin Pharmacother 2017; 29(10):1-12.
• ⁵⁷
  Cheng G, Huang C, Deng H, Wang H. Diabetes as a risk factor for dementia and mild cognitive impairment: A meta-analysis of longitudinal studies. Intern Med J 2012; 42(5):484-491.
• ⁵⁸
  Kuchemann BA. Envelhecimento populacional, cuidado e cidadania: velhos dilemas e novos desafios. Revista Sociedade e Estado 2012; 27(1):165-180.
• ⁵⁹
  Holz AW, Nunes BO, Thumé E, Lange C, Facchini LA. Prevalência de déficit cognitivo e fatores associados entre idosos de Bagé, Rio Grande do Sul, Brasil. Rev Bras Epidemiol 2013; 16(4):880-888.
• ⁶⁰
  Veras BP, Caldas CP, Dantas S, Sancho LG, Sicsú B, Motta LB. Demented elderly people living at home in Rio de Janeiro, Brazil: Evaluation of expenditure care. Psychogeriatrics 2008; 8(2):88-95.
• ⁶¹
  Meek PD, McKeithan K, Schumock GT. Economic considerations in Alzheimer’s disease. Pharmacotherapy 1998; 18(Pt. 2):68-73.
• ⁶²
  Brookmeyer R, Gray S, Kawas C. Projections of Alzheimer’s disease in the United States and the public health impact of delaying disease onset. Am J Public Health 1998; 88(9):1337-1342.
• ⁶³
  McCallion H. Dementia Training. Mental Health Practice 2009; 12(7):8.
• ⁶⁴
  Hux MJ, O’Brien BJ, Iskedjian M, Goeree R, Gagnon M, Gauthier S. Relation between severity of Alzheimer’s disease and costs of caring. CMAJ 1998; 159(5):457-465.

Publication Dates

• Publication in this collection
  03 Feb 2020
• Date of issue
  Feb 2020

History

• Received
  21 Mar 2018
• Accepted
  16 May 2018
• Published
  18 May 2018