Risk Factors Profile in Dementia Patients at a Tertiary Care Hospital in Nepal: A Cross-Sectional Study

Abstract

Dementia is attributable to 12 known risk factors in 40% cases. This study aimed to assess the prevalence of defined risk factors among people living with dementia. 174 patients with dementia and caregivers were interviewed using semi-structured pro forma, risk factors provided by the Lancet Commission on Dementia (2020), and Dementia Severity Rating Scale (DSRS). The prevalence of 11 known risk factors and associations between the risk factors and dementia severity were assessed. The mean age of the participants was 73.9 years (SD = 8.34 years). The education below intermediate level was 83.3%, 17.8% had hearing loss, 37.9% had hypertension, 24.1% had diabetes, 25.9% and 55.2% had alcohol and nicotine harmful use respectively and 8% had a history of traumatic brain injury and obesity each. There is a substantial prevalence of risk factors among people living with dementia in Nepal but no associations between any of the risk factors and dementia severity.

Keywords

risk factors dementia caregivers dementia prevention dementia severity

Introduction

Dementia is a general term for the new-onset problem of memory, language, behavior, problem-solving, and other thinking abilities that is severe enough to interfere with daily life. It is a syndrome of a chronic or progressive nature that leads to deterioration in cognitive function beyond what might be expected from the usual consequences of biological aging.¹ Worldwide around 50 million people live with dementia and this number is projected to increase to 152 million by 2050, particularly in low-income and middle-income countries (LMIC).² According to the 2001 census of Nepal, there was 6.5% (1.5 million) geriatric population (>60 years) which has increased to 10.2% (2.97 million) in 2021.³ Dementia affects individuals, their families, and the economy, with global costs estimated to be about US$1 trillion annually² and contributes to 4.1% of total disability-adjusted life years (DALYs).⁴ On the contrary, dementia is under-recognized, under-disclosed, undertreated, and undermanaged, particularly in LMICs, and considered a part of normal aging rather than requiring medical care.⁵

Various risk factors are considered to be associated with an increased incidence of dementia. The 2020 report of the Lancet Commission on Dementia prevention, intervention, and care, has identified 12 modifiable risk factors of dementia, which include less education, hypertension, hearing impairment, smoking, obesity, depression, physical inactivity, diabetes, low social contact, excessive alcohol consumption, traumatic brain injury (TBI), and air pollution. These modifiable risk factors might prevent or delay up to 40% of dementia.⁶

Given the expanding geriatric demographic in Nepal, pinpointing modifiable risk factors pertinent to this population may yield critical insights for public health interventions in resource-constrained environments. This research aimed to study the prevalence of modifiable risk factors of dementia among people living with dementia and its association with the severity of dementia. Knowledge about the prevalence of risk factors would help us to lay a baseline understanding for further research on the primary prevention of dementia in our setting. The number of published literature regarding pathways to care and risk factors of dementia in Nepal was scanty, to the best of our knowledge.

Methodology

This was a cross-sectional study conducted at Patan Academy of Health Sciences (PAHS) from April 2022 to March 2023. The main objective of the study was to assess the prevalence of defined risk factors among people living with dementia attending Patan Hospital in 1 year. The out-patient department (OPD) and in-patient cases, diagnosed as dementia by consultant psychiatrist as per ICD 10 criteria were included. The only exclusion criterion was the refusal of written consent by participants or caregivers. Over 1 year, 174 people living with dementia were interviewed and included in the study. Approval of the study was obtained from the Institutional Review Committee (IRC) of PAHS (Ref: PMS2203041595). The participants and their caregivers had the study explained to them in detail before obtaining the informed written consent. For informed written consent, a generic PAHS consent form in Nepali was used. If participants wished, they were allowed to withdraw at any time without any reason. We guaranteed the confidentiality of all the participants. They were interviewed using semi-structured pro forma including the risk factors for dementia as provided by the 2020 report of the Lancet Commission on Dementia, and Dementia Severity Rating Scale (DSRS) was applied. DSRS has 12 items scored 0-3 to 0-6 in different items. The score is categorized as mild (0-18), moderate (19-36), and severe (37-54) dementia.⁷ Data was analyzed using SPSS. Categorical data were presented in frequency and percentage while continuous data were summarized in mean and SD for parametric data or median with interquartile range for non-parametric data. The association between risk factors and the severity of dementia was explored and analyzed by using the Chi-square test or Fisher exact test. The P-value less than 0.05 was considered significant.

Result

The mean age of the participants was 73.9 years and most of them (73.6%) were between the age group of 60-80 years. The majority were male (51.7%), married (61.5%), and living in a joint family (77.6%). (Figure 1)

Figure 1.

Risk Factors Profile in People Living With Dementia Attending Tertiary Care Hospital (n = 174).

The most prevalent risk factors in a tertiary hospital in Nepal were education below intermediate in 83.3%, history of nicotine harmful use or dependence in 55.2%, 37.9% had hypertension, and history of alcohol harmful use or dependence in 25.9%. All in all, Table 1 shows no statistically significant associations between risk factors and dementia severity (P > 0.05 for all).

Table 1.

Association Between the Risk Factors and Severity of Dementia in People Living With Dementia Attending Tertiary Level Hospital (n = 174).

Risk factors		DSRS			P-value
Risk factors		Mild	Moderate	Severe	P-value
Education	Below intermediate level	17 (11.7%)	84 (57.9%)	44 (30.4%)	0.075
Education	Intermediate level/above	8 (27.6%)	15 (51.7%)	6 (20.7%)	0.075
Hearing loss	Yes	2^a (6.5%)	17 (54.8%)	12 (38.7%)	0.251
Hearing loss	No	23 (16.1%)	82 (57.3%)	38 (26.6%)	0.251
Hypertension	Yes	10 (15.2%)	37 (56.1%)	19 (28.7%)	0.971
Hypertension	No	15 (13.9%)	62 (57.4%)	31 (28.7%)	0.971
History of alcohol harmful use or dependence	Yes	5 (11.1%)	30 (66.7%)	10 (22.2)	0.307
History of alcohol harmful use or dependence	No	20 (15.5%)	69 (53.5%)	40 (31%)	0.307
Obesity	Yes	1^a (7.1%)	10 (71.4%)	3^a (21.5%)	0.577
Obesity	No	24 (15%)	89 (55.6%)	47 (29.4%)	0.577
History of TBI	Yes	2^a (14.3%)	9 (64.3%)	3^a (21.4%)	0.924
History of TBI	No	23 (14.4%)	90 (56.3%)	47 (29.3%)	0.924
Diabetes mellitus	Yes	4^a (9.5%)	28 (66.7%)	10 (23.8%)	0.317
Diabetes mellitus	No	21 (15.9%)	71 (53.8%)	40 (30.3%)	0.317
History of nicotine harmful use or dependence	Yes	12 (12.5%)	59 (61.5%)	25 (26%)	0.398
History of nicotine harmful use or dependence	No	13 (16.7%)	40 (51.3%)	25 (32%)	0.398
History of depression	Yes	3^a (20%)	9 (60%)	3^a (20%)	0.645
History of depression	No	22 (13.8%)	90 (56.6%)	47 (29.6%)	0.645
Perceived social isolation	Socially inactive	1^a (11.1%)	5 (55.6%)	3^a (33.3%)	1.000
Perceived social isolation	Socially active	24 (14.5%)	94 (57%)	47 (28.5%)	1.000
Perceived physical activity	Physically inactive	1^a (16.7%)	2^a (33.3%)	3^a (50%)	0.412
Perceived physical activity	Physically active	24 (14.3%)	97 (57.7%)	47 (28%)	0.412

^a= Since value in individual cell <5, Fisher’s exact test used.

Discussion

In this hospital-based cross-sectional study, the mean age of the participants was 73.9 years (SD = 8.3 years) which is comparable with other studies in Nepal and India.⁸ The comparable age for patients in the Indian population could be because of our similarities in life expectancy and lifestyle.^3,9 In a study done in the USA, the mean age was 83.1 years, which is higher than our study.¹⁰ This can be due to the sample selection of advanced dementia, nutritional status, and life-expectancy differences.

The majority of the participants (77.6%) in this study were from a joint family (married couples and their children living in the same household, where all the men in the household are related by blood and the women are their wives, unmarried daughters or widows¹¹) which is per our socio-cultural background of staying in a joint family. In this study, most of the participants were married (61.5%) followed by widow/widower (37.9%) which was similar to other studies done in tertiary hospitals in Nepal and India.^12,13

In this study, eleven risk factors were evaluated in the participants. Most of the participants (83.3%) were educated below intermediate (high-school) level. A similar finding was seen in a descriptive cross-sectional study done in an OPD of another tertiary care hospital in Nepal.¹⁴ Most participants did not have formal education or were below intermediate level due to limited educational institutions during that time i.e. almost half a century back and socio-cultural factors like lack of knowledge of the importance of education. The higher the education, the higher the intellectual capacity, occupational complexity, and engagement in intellectually and cognitively stimulating activities, which increases the cognitive reserve and brain plasticity.¹⁵

The prevalence of hearing loss in this study was 17.8%. In a study done in 2020, hearing loss accounted for 8.2% of dementia cases.⁶ It is known that even subclinical levels of hearing impairment (below 25 dB) were related to lower cognition.¹⁶ Timely treatment of hearing loss can reduce new dementia cases by 9.1%, the largest reduction among all known modifiable risk factors.¹⁷

It was seen that 37.9% of the participants in our study had hypertension and were under medication, where the duration of hypertension was from 2 years to 43 years. A study done in India and USA showed hypertension prevalence to be 55.3% and 66% respectively.^18,19 The difference might be due to help-seeking behavior, socio-economic and lifestyle factors. Midlife and late-life hypertension are associated with an increased risk of late-life dementia.²⁰ The mechanism is neurovascular damage, focal brain atrophy, β-amyloid, and tau neuropathology.²¹ With proper treatment of hypertension, the incidence of cognitive impairment decreases (HR 0·8; 95% CI 0·7-1·0).²²

In this study, 42 out of 174 participants (24.1%) were diabetic for 1 to 39 years. A case-control study done in India showed 33.3% prevalence of diabetes in dementia cases.¹⁹ An American longitudinal study showed the prevalence of diabetes in dementia to be 28%.¹⁸ The variations might be due to eating habits, early recognition, and treatment of diabetes in other countries. The risk of dementia increases with the duration and severity of diabetes.²³ The underlying pathophysiology are vascular mechanisms, toxic effects of hyperglycemia/hypoglycemia, insulin resistance of the brain, formation of advanced glycation end products, and competition for insulin-degrading enzyme resulting in reduced degradation of -amyloid, but none of these has been proven unequivocally.²⁴

Obesity was seen in 8% of the participants at the time of presentation, which was similar even before the onset of dementia according to the caregivers. This finding is similar to a study from China where the prevalence of obesity was 9.5% in dementia patients.²⁵ In the English Longitudinal Study of Ageing (ELSA) 29.6% of dementia patients were obese. This difference might be due to eating habits and lifestyle differences.²⁶ Obesity is associated with brain atrophy, white matter changes, disturbances of blood-brain barrier integrity, and increased incidence of hypertension, diabetes, and coronary artery disease, which increases the risk of all-cause late-onset dementia.²⁷ Intentional weight loss in obese/overweight people is associated with improvements in performance across various cognitive domains and decreases the risk of dementia.²⁸

It was seen that 8% of participants in this study had TBI prior to the onset of dementia. A case control study done in India showed the prevalence of TBI in 15% of participants with dementia.¹⁹ Similar to this study, a nationwide cohort study in Sweden showed the prevalence of TBI as a risk factor in 6.3%.²⁹ TBI increases the risk of dementia by widespread hyperphosphorylated tau pathology in the brain.³⁰

Among the participants, 25.9% fulfilled the criteria of alcohol harmful use or dependence in this study. In a case-control study in India, the prevalence was 19.3%.¹⁹ In a nationwide retrospective cohort study done in France, the prevalence of alcohol use disorder was 38.9%.³¹ The differences might be due to socio-cultural factors and the availability of alcohol. Alcohol is known to cause neurotoxicity, thiamine deficiency, and brain atrophy, leading to cognitive impairment and early abstinence can decrease the risk.^32,33

Nicotine consumption was the most common modifiable risk factor, identified in 55.2% of subjects, including nicotine harmful use or dependence. A case-control study in India showed nicotine dependence or harmful use in 33.3% of cases.¹⁹ The number is higher than alcohol consumption due to easy availability, consideration of nicotine as a non-psychoactive substance, and a significant number of females along with males, consuming tobacco. A population-based cohort study conducted in seven LMICs as part of the 10/66 Dementia Research showed no significant association between smoking and the onset of any dementia.³⁴ Smoking cigarettes causes oxidative stress and systemic inflammation, responsible for dementia in both active and passive smokers.³⁵ Early cessation of smoking is seen to decrease the risk of dementia in the future.³⁶

A history of depression diagnosed by health professionals prior to the onset of dementia was seen in 8.6% of the participants. Similar findings were seen in the Longitudinal Ageing Study in India (LASI) Wave 1 (2017-18) including 31 464 participants and in a nationwide study done in Sweden in 41 727 dementia patients.^37,38 Depression can be a prodrome of dementia and there can be reverse causation between depression and dementia.⁶ The possible mechanisms for depression to be the risk factor for dementia are hippocampal atrophy, increased amyloid plaques, pro-inflammatory changes in the brain, among others.³⁹ Adequate treatment of depression with SSRI reduces the risk and delay the progression of dementia.⁴⁰

Among 174 participants, 9 (5.2%) were identified to be socially isolated as perceived by the care-givers. The isolation was not due to socio-cultural aspects but individual preference. Social contact is accepted as a protective factor against dementia by enhancing cognitive reserve. At times, social isolation might also occur in the prodrome of dementia⁶ which should be properly identified.

In this study, 6 participants (3.4%) were physically inactive as perceived by the caregivers. Exercise is associated with a reduced risk of dementia.¹⁷ Aerobic exercise was seen to be better than resistance exercise and 30 minutes per day for 5 days in a week of moderate to vigorous exercise decreases the risk of dementia.^41,42 These modifiable risk factors account for about 40% of worldwide dementias, which could theoretically be prevented or delayed.⁶ The prevention strategy is more applicable in LMIC as many of the risk factors are more prevalent and dementia cases are ever-increasing in this part of the world.

The final objective of this study was to assess the association between risk factors and severity of dementia, where no statistically significant association was found. The risk factors were known to increase the risk of dementia⁶ but as per this study, dementia severity was not associated with the risk factors profile. As such, on a thorough search in PubMed, Google Scholar, and NepJOL we could not find studies assessing the association between risk factors and dementia severity.

Strengths of the Study

This was a unique study in Nepal, as per the search in NepJOL, Google Scholar, and PubMed there have been no studies assessing the aforementioned risk factors profile, and association of risk factors with the severity of dementia, done in Nepal. The participants were diagnosed by consultant psychiatrists using ICD-10 criteria making the diagnosis reliable. The use of DSRS with good psychometric properties and consideration of risk factors as provided by 2020 report of the Lancet Commission on Dementia made the study more objective. The sample size was also adequate as per the prevalence of dementia in a previous study done in Nepal.

Limitations of the Study

There were some limitations in this study. This is a cross-sectional study conducted in a tertiary hospital, so the results of the study cannot be applied to the general population. The sampling method used was convenience sampling, which could have led to selection bias, perhaps failing to represent the wider population of people living with dementia in Nepal. This is neither a cohort nor a case-control study, so attributable risk could not be determined. There could be recall bias in reports of the caregivers regarding past facts, for example, onset, duration, and presence of risk factors (though physician records corroborated most). The risk factors were not analyzed with types of dementia. Similarly, the exploration of risk factors associated with dementia severity was not adjusted for age of the patient or time since diagnosis. Regarding obesity, we had to measure current BMI and ask caregivers if it was similar in the past which could have been different and caused the bias in the results. Physical activity and social isolation were quantified as per the caregivers’ perception which doesn’t have a good validity as compared to the real-time measure. Though the scales used have good psychometric properties, they were not validated in the Nepalese setting. Among 12 risk factors discussed by the 2020 report of the Lancet Commission on Dementia prevention, intervention and care, we included only 11, excluding “air pollution”, as there was no reliable way to quantify air pollution and the residence of the participants would change often.

Conclusion

In this study, we assessed the risk factors profile of people living with dementia who presented to a tertiary care hospital and also assessed the association between risk factors and the severity of dementia. Majority of the participants were male, married, between 60-80 years age group, living in a joint family and taken care by their children. All the studied risk factors were prevalent in our sample. The significant prevalence of modifiable risk factors such as lower education, smoking and hypertension highlights the necessity for targeted public health interventions aimed at early prevention, particularly in resource-constrained environments like Nepal. The majority (56.9%) of the participants had moderate severity of dementia according to the DSRS score. The risk factors were common in the sample, but there was no association between the risk factors and dementia severity.

Recommendation and Future Direction

Early identification and prevention or management of risk factors can prevent dementia significantly and minimize the social and economic burden of care. It is more applicable to the LMIC like ours, as the greying population is ever increasing and treatment gap is high. There should be specific policy from the government to assess the risk factors in mid-life and cognitive impairment in late-life, so that early identification and management of risk factors could be done. To get a better understanding of the risk factors and dementia, we recommend cohort studies/RCTs, multi-centric studies in the general population and in the community, to generalize the result. This study can be a foundation for further research on risk factors in people living with dementia in Nepal and formulation of National dementia care plan.

Footnotes

Acknowledgments

To the entire department of psychiatry of PAHS and all the participants of this study.

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

Ethical Statement

ORCID iD

Omkar Dhungel

Data Availability Statement

Data will be shared upon reasonable request by the corresponding author.*

References

Dementia. Accessed November 13, 2021. https://www.who.int/news-room/fact-sheets/detail/dementia

International AD Patterson

. World Alzheimer report 2018: the state of the art of dementia research: new frontiers. https://www.alzint.org/resource/world-alzheimer-report-2018/. Published online September 21, 2018. Accessed November 13, 2021.

Central Bureau of Statistics – Central Bureau of Statistics . Accessed November 13, 2021. https://cbs.gov.np/

World Health Organization . The Global Burden of Disease: 2004 Update. Geneva: World Health Organization; 2008. https://apps.who.int/iris/handle/10665/43942. Accessed November 13, 2021.

Comas-Herrera

Guerchet

Karagiannidou

Knapp

Prince

. World Alzheimer Report 2016: improving healthcare for people living with dementia: coverage, quality and costs now and in the future. https://www.alzint.org/resource/world-alzheimer-report-2016/. Published online September 21, 2016. Accessed November 13, 2021.

Livingston

Huntley

Sommerlad

, et al. Dementia prevention, intervention, and care: 2020 report of the lancet commission. Lancet. 2020;396(10248):413-446.

Clark

Ewbank

. Performance of the dementia severity rating scale: a caregiver questionnaire for rating severity in Alzheimer disease. Alzheimer Dis Assoc Disord. 1996;10(1):31-39.

Vas

Pinto

Panikker

, et al. Prevalence of dementia in an urban Indian population. Int Psychogeriatr. 2001;13(4):439-450.

https://data.who.int/countries/356.

10.

Kroenke

Gao

Mosesso

, et al. Prevalence and predictors of symptoms in persons with advanced dementia living in the community. J Palliat Med. 2022;25(9):1376-1385.

11.

Park’s

. K P. Park’s text book of preventive and social medicine. https://localhost:8081/xmlui/handle/123456789/355. Published online January 7, 2021. Accessed February 3, 2022.

12.

Hossien

Loganathan

Kolar Sridara Murthy

Palanimuthu Thangaraju

Bharath

Varghese

. Pathways to care among persons with dementia: study from a tertiary care center. Asian J Psychiatr. 2017;30:59-64.

13.

Nepal

Sapkota

. Prevalence of dementia among elderly patients attending psychiatry OPD of tertiary care hospital and its association with socio demographic variables. J Psychiatr Assoc Nepal. 2018;6(1):12-17.

14.

Belbase

Adhikari

. Dementia in 50 years and older patients from the psychiatry out patient department of a tertiary care center: a descriptive cross-sectional study. J Nepal Med Assoc JNMA. 2021;59(242):979-982.

15.

Kremen

Beck

Elman

, et al. Influence of young adult cognitive ability and additional education on later-life cognition. Proc Natl Acad Sci USA. 2019;116(6):2021-2026.

16.

Golub

Brickman

Ciarleglio

Schupf

Luchsinger

. Association of subclinical hearing loss with cognitive performance. JAMA Otolaryngol Head Neck Surg. 2020;146(1):57-67.

17.

Livingston

Sommerlad

Orgeta

, et al. Dementia prevention, intervention, and care. Lancet. 2017;390(10113):2673-2734.

18.

Sutin

Stephan

Luchetti

Terracciano

. Loneliness and risk of dementia. J Gerontol B Psychol Sci Soc Sci. 2020;75(7):1414-1422.

19.

Tripathi

Vibha

Gupta

, et al. Risk factors of dementia in North India: a case–control study. Aging Ment Health. 2012;16(2):228-235.

20.

McGrath

Beiser

DeCarli

, et al. Blood pressure from mid‐ to late life and risk of incident dementia. Neurology. 2017;89(24):2447-2454.

21.

Blennow

De Leon

Zetterberg

. Alzheimer’s disease. Lancet. 2006;368(9533):387-403.

22.

in't Veld

Ruitenberg

Hofman

Stricker

BHC

Breteler

MMB

. Antihypertensive drugs and incidence of dementia: the Rotterdam Study. Neurobiol Aging. 2001;22(3):407-412.

23.

McMillan

Mele

Hogan

Leung

. Impact of pharmacological treatment of diabetes mellitus on dementia risk: systematic review and meta-analysis. BMJ Open Diab Res Care. 2018;6(1):e000563.

24.

Ahtiluoto

Polvikoski

Peltonen

, et al. Diabetes, Alzheimer disease, and vascular dementia: a population-based neuropathologic study. Neurology. 2010;75(13):1195-1202.

25.

Hou

Guan

, et al. Associations between obesity and cognitive impairment in the Chinese elderly: an observational study. CIA. 2019;14:367-373.

26.

Ajnakina

Steptoe

Cadar

. Higher risk of dementia in English older individuals who are overweight or obese. Int J Epidemiol. 2020;49(4):1353-1365.

27.

Kiliaan

Arnoldussen

IAC

Gustafson

. Adipokines: a link between obesity and dementia? Lancet Neurol. 2014;13(9):913-923.

28.

Veronese

Facchini

Stubbs

, et al. Weight loss is associated with improvements in cognitive function among overweight and obese people: a systematic review and meta-analysis. Neurosci Biobehav Rev. 2017;72:87-94.

29.

Nordström

. Traumatic brain injury and the risk of dementia diagnosis: a nationwide cohort study. PLoS Med. 2018;15(1):e1002496.

30.

Zanier

Bertani

Sammali

, et al. Induction of a transmissible tau pathology by traumatic brain injury. Brain. 2018;141:2685-2699.

31.

Schwarzinger

Pollock

Hasan

OSM

Dufouil

Rehm

QalyDays Study Group . Contribution of alcohol use disorders to the burden of dementia in France 2008-13: a nationwide retrospective cohort study. Lancet Public Health. 2018;3(3):e124-e132.

32.

Topiwala

Allan

Valkanova

, et al. Moderate alcohol consumption as risk factor for adverse brain outcomes and cognitive decline: longitudinal cohort study. BMJ. 2017;357:j2353.

33.

Ridley

Draper

Withall

. Alcohol-related dementia: an update of the evidence. Alzheimers Res Ther. 2013;5(1):3.

34.

Otuyama

Oliveira

Locatelli

, et al. Tobacco smoking and risk for dementia: evidence from the 10/66 population-based longitudinal study. Aging Ment Health. 2020;24(11):1796-1806.

35.

Hahad

Daiber

Michal

, et al. Smoking and neuropsychiatric disease—associations and underlying mechanisms. IJMS. 2021;22(14):7272.

36.

Deal

Power

Palta

, et al. Relationship of cigarette smoking and time of quitting with incident dementia and cognitive decline. J Am Geriatr Soc. 2020;68(2):337-345.

37.

Yang

Pan

, et al. Association of life‐course depression with the risk of dementia in late life: a nationwide twin study. Alzheimers Dement. 2021;17(8):1383-1390.

38.

Saravanakumar

Muhammad

Paul

Srivastava

. Explaining the urban-rural difference in late-life depression in India: evidence from a multivariate decomposition analysis based on longitudinal aging study in India, Wave 2017-18. Clin Gerontol. 2024;47:270-287.

39.

Byers

Yaffe

. Depression and risk of developing dementia. Nat Rev Neurol. 2011;7(6):323-331.

40.

Bartels

Wagner

Wolfsgruber

Ehrenreich

Schneider

Alzheimer’s Disease Neuroimaging Initiative . Impact of SSRI therapy on risk of conversion from mild cognitive impairment to Alzheimer’s dementia in individuals with previous depression. Aust J Pharm. 2018;175(3):232-241.

41.

Barha

Davis

Falck

Nagamatsu

Liu-Ambrose

. Sex differences in exercise efficacy to improve cognition: a systematic review and meta-analysis of randomized controlled trials in older humans. Front Neuroendocrinol. 2017;46:71-85.

42.

Zotcheva

Bergh

Selbæk

, et al. Midlife physical activity, psychological distress, and dementia risk: the HUNT study. JAD. 2018;66(2):825-833.