DESK REVIEWS | 06.02.12. What risk factors have been associated with dementia?

DESK REVIEW | 06.02.12. What risk factors have been associated with dementia?

Longitudinal studies on dementia identified the following as risk factors: advanced age (Nitrini et al., 2004) and years of education (Chaves et al., 2009).

References:

Chaves, M. L., Camozzato, A. L., Godinho, C., Piazenski, I., & Kaye, J. (2009). Incidence of Mild Cognitive Impairment and Alzheimer Disease in Southern Brazil. Journal of Geriatric Psychiatry and Neurology, 22(3), 181–187. https://doi.org/10.1177/0891988709332942

Nitrini, R., Caramelli, P., Herrera, E., Bahia, V. S., Caixeta, L. F., Radanovic, M., Anghinah, R., Charchat-Fichman, H., Porto, C. S., Carthery, M. T., Hartmann, A. P. J., Huang, N., Smid, J., Lima, E. P., Takada, L. T., & Takahashi, D. Y. (2004). Incidence of dementia in a community-dwelling Brazilian population. Alzheimer Disease and Associated Disorders, 18(4), 241–246.

Few studies have examined the associations of various factors with mild cognitive impairment/dementia across different regions in India. This has been summarised in Table 6.4.

Table 6.4.

Associations with MCI/ dementia City/State Study was conducted Description
Gender All states, India The GBD 2019 study provides a state wise prevalence of dementia across India, demonstrating that the prevalence of dementia is consistently higher in females than males (India State-Level Disease Burden Initiative Neurological Disorders Collaborators, 2021)
Hypertension and diabetes Kolkata, West Bengal Community-based study identified risk factors for mild cognitive impairment (MCI) to be hypertension and diabetes mellitus (Das et al., 2007).
Ernakulam, Kerala A univariate analysis done as part of another comparative study showed that hypertension had a significant association with dementia (Lalu et al., 2018).
Obesity New Delhi, Delhi Most participants (68%) with vascular dementia were obese in a study conducted in memory clinic of a tertiary care hospital. The study concluded that obesity is common in persons with vascular dementia and needs to be addressed as it can independently contribute to vascular dementia (Chandra and Anand, 2015).
New Delhi, Delhi A case control study identified higher BMI to be associated with greater risk for dementia (Tripathi et al., 2012).
Hearing Loss Ernakulam, Kerala A univariate analysis as part of a comparative study of risk factors in dementia patients and control group found hearing loss to be a risk factor for dementia (Lalu et al., 2018).
Education (association with dementia shows mixed results) Ernakulam, Kerala A univariate analysis as part of a comparative study of risk factors for dementia patients and a control population found a significant association between dementia and education (Lalu et al., 2018).
Hyderabad, Telangana Examination of cases records of 648 dementia patients showed relationship between dementia and education is context-dependent, influenced by LSES, CVD and bilingualism (Iyer et al., 2014).
Hassan district, Karnataka A higher prevalence of

dementia was found among illiterates (7.4%) (Sumana et al., 2016).

Depression Ludhiana, Punjab Cognitively impaired older adults were found to be 3 times at risk of developing depression and furthermore depression was associated with

cognitive impairment (Sengupta and Benjamin, 2015).

Low socioeconomic status Ludhiana, Punjab Poverty and illiteracy were reported to be associated with cognitive impairment (Sengupta et al., 2014).
Smoking Kolkata, West Bengal

 

Inhaling and chewing of tobacco— was a risk factor among dementia patients when compared to the control population in an epidemiological study of mild cognitive impairment (Das et al., 2007).
Kerala Smoking was identified to be associated with vascular dementia in an epidemiological study of dementia prevalence in rural Kerala (Shaji et al., 1996).
Physical inactivity Ernakulam, Kerala Univariate analysis has demonstrated poor levels of physical activity have been identified as an independent risk factor for dementia (Lalu et al., 2018).

Source: (Das et al., 2007; India State-Level Disease Burden Initiative Neurological Disorders Collaborators, 2021; Iyer et al., 2014; Lalu et al., 2018; Sengupta et al., 2014; Sengupta and Benjamin, 2015; Shaji et al., 1996; Sumana et al., 2016)

In addition, a cross-sectional study of potentially modifiable risk factors for dementia reported less education, hearing impairment, depression, and physical inactivity, in particular, to be associated with increased odds of dementia in India (Belessiotis-Richards et al., 2021).

The risk factors in Table 6.4 are similar to previously identified potentially modifiable risk factors (low education in early life, mid-life hearing loss, mid-life hypertension, mid-life obesity, later-life smoking, later-life depression, later-life physical inactivity, later-life social isolation and later-life diabetes) for dementia, which, if addressed, may delay up to 41% of dementia in India (Mukadam et al., 2019).

References:

Chandra, M., & Anand, K. S. (2015). Obesity in Indian subjects with vascular dementia. International Journal of Advances in Medicine2(2), 147.

Belessiotis-Richards, C., Livingston, G., Marston, L., & Mukadam, N. (2021). A cross-sectional study of potentially modifiable risk factors for dementia and cognitive function in India: A secondary analysis of 10/66, LASI, and SAGE data. International journal of geriatric psychiatry37(2), 10.1002/gps.5661. Advance online publication. https://doi.org/10.1002/gps.5661

Das, S. K., Bose, P., Biswas, A., Dutt, A., Banerjee, T. K., Hazra, A. M., …& Roy, T. (2007). An epidemiologic study of mild cognitive impairment in Kolkata, India. Neurology, 68(23), 2019–2026. https://doi.org/10.1212/01.wnl.0000264424.76759.e6

India State-Level Disease Burden Initiative Neurological Disorders Collaborators (2021). The burden of neurological disorders across the states of India: The Global Burden of Disease Study 1990-2019. The Lancet. Global health, 9(8), e1129–e1144.

Iyer, G. K., Alladi, S., Bak, T. H., Shailaja, M., Mamidipudi, A., Rajan, A., … & Kaul, S. (2014). Dementia in developing countries: Does education play the same role in India as in the West? Dementia & Neuropsychologia, 8(2), 132–140. https://doi.org/10.1590/S1980-57642014DN82000008

Lalu, J. S., Vijayakumar, P., George, S., Nair, A. V., & B., A. (2018). Risk factors of dementia: a comparative study among the geriatric age group in Ernakulam, Southern India. International Journal Of Community Medicine And Public Health, 5(2), 544. https://doi.org/10.18203/2394-6040.ijcmph20180117

Livingston, G., Huntley, J., Sommerlad, A., Ames, D., Ballard, C., Banerjee, S., … & Mukadam, N. (2020). Dementia prevention, intervention, and care: 2020 report of the Lancet Commission. The Lancet, 396(10248), 413-446.

Mukadam, N., Sommerlad, A., Huntley, J., & Livingston, G. (2019). Population attributable fractions for risk factors for dementia in low-income and middle-income countries: an analysis using cross-sectional survey data. The Lancet Global Health7(5), e596-e603.

Sengupta, P., & Benjamin, A. I. (2015). Prevalence of depression and associated risk factors among the elderly in urban and rural field practice areas of a tertiary care institution in Ludhiana. Indian journal of public health59(1), 3. https://doi.org/10.4103/0019-557X.152845

Sengupta, P., Benjamin, A. I., Singh, Y., & Grover, A. (2014). Prevalence and correlates of cognitive impairment in a north Indian elderly population. WHO South-East Asia journal of public health3(2), 135-143. https://doi.org/10.4103/2224-3151.206729

Shaji, S., Promodu, K., Abraham, T., Roy, K. J., & Verghese, A. (1996). An Epidemiological Study of Dementia in a Rural Community in Kerala, India. British Journal of Psychiatry, 168(6), 745–749. https://doi.org/10.1192/bjp.168.6.745.

Sumana, M., Sreelatha, C.Y., Sreeranga, A., Arpitha,B., Akshatha, S., & Anand, H. (2016). Prevalence of dementia and other psychiatric morbidities among geriatric population of Salagame primary health centre in Hassan district, Karnataka, India. International Journal of Community Medicine and Public Health, 3(5), 1315–1317. https://doi.org/10.18203/2394-6040.ijcmph20161404

Tripathi, M., Vibha, D., Gupta, P., Bhatia, R., Srivastava, M.V.P., Vivekanandhan, S., Bhushan Singh, M., Prasad, K., Dergalust, S., Mendez, M.F. (2012). Risk factors of dementia in North India: a case–control study. Aging Ment. Health 16, 228–235. https://doi.org/10.1080/13607863.2011.583632

The national dementia strategy document mentioned several risk factors which can affect brain health negatively over the life course. These including congenital anomaly, genetics, smoking, alcohol, malnutrition, non-communicable and communicable diseases, metabolic diseases, vascular, and neurological disorders (Ministry of Health Republic of Indonesia, 2015b).

Surveymeter’s study in Bali shows that 47.6% of respondents diagnosed with dementia reported a comorbidity with stroke, followed by 40% with cancer, 38.8% heart disease, and 34.6% hypertension. However, the study did not investigate the association between these possible risk factors with dementia (Suriastini et al., 2018). Other studies in different populations have also reported the association with hypertension (Fitri & Rambe, 2018), diabetes (Kayo et al., 2012), and dyslipidemia (Maryam & Sahar, 2019). Moreover, according to Turana et al., 2019, the highest estimated population-attributable risks are low education, smoking, and physical inactivity (Turana et al., 2019).

References:

Fitri, F. I., & Rambe, A. S. (2018). Correlation between hypertension and cognitive function in elderly. IOP Conference Series: Earth and Environmental Science, 125(1). https://doi.org/10.1088/1755-1315/125/1/012177

Kayo, A. R., Wimala, A. R., Angela, N., & Rashid, I. binti A. (2012). Random blood glucose level as predictor of cognitive impairment in elderly. Universa Medicina, 31(2), 131–138. https://doi.org/10.1805/UnivMed.2012.v31.131-138

Maryam, R. S., & Sahar, J. (2019). Determining factors of dementia in elderly individuals residing in the special capital region of Jakarta. Enfermería Clínica.

Ministry of Health Republic of Indonesia. (2015b). National Strategy: Management of Alzheimer and Other Dementia Diseases: Towards Healthy and Productive Older Persons. Ministry of Health Republic of Indonesia.

Suriastini, Turana, Y., Sukadana, W., Sikoki, B., Witoelar, F., Lesmana, C. B. J., Mulyanto, E. D., Hermoko, R., & Anandari, G. A. A. A. (2018). Menggugah Lahirnya Kebijakan Kelanjutusiaan Menggugah Lahirnya Kebijakan Kelanjutusiaan.

Turana, Y., Tengkawan, J., Suswanti, I., Suharya, D., Riyadina, W., & Pradono, J. (2019). Primary Prevention of Alzheimer’s Disease in Indonesia. International Journal of Aging Research, 1–8. https://doi.org/10.28933/ijoar-2019-06-2506

Increasing age, illiteracy, vascular disease, low-fiber diet, depression, and genetic factors (presence of APOE-𝜀4 allele) have been identified as risk factors for dementia in two reviews on epidemiology of dementia in Sub-Saharan Africa and developing countries (three studies included findings from Kenya) (Kalaria et al., 2008; Olayinka & Mbuyi, 2014). A study conducted in Kenya revealed that there was no evidence between education or vascular factors and dementia status (Chen et al., 2010). According to a systematic analysis for the global burden of disease study involving 195 countries (including Kenya) in 2016, the four main risk identified to have a causal link to Alzheimer’s disease and other dementias are high Body Mass Index (BMI), high fasting plasma glucose, smoking, and high intake of sugar-sweetened beverages (Nichols et al., 2019). More studies are required to confirm inconsistencies in earlier findings.

References:

Chen, C.-H., Mizuno, T., Elston, R., Kariuki, M. M., Hall, K., Unverzagt, F., … Patel, N. B. (2010). A comparative study to screen dementia and APOE genotypes in an ageing East African population. Neurobiology of Aging, 31(5), 732–740. https://doi.org/10.1016/j.neurobiolaging.2008.06.014

Kalaria, R. N., Maestre, G. E., Arizaga, R., Friedland, R. P., Galasko, D., Hall, K., … Potocnik, F. (2008). Alzheimer’s disease and vascular dementia in developing countries: prevalence, management, and risk factors. The Lancet Neurology, 7(9), 812–826. https://doi.org/10.1016/S1474-4422(08)70169-8

Nichols, E., Szoeke, C. E. I., Vollset, S. E., Abbasi, N., Abd-Allah, F., Abdela, J., … Murray, C. J. L. (2019). Global, regional, and national burden of Alzheimer’s disease and other dementias, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. The Lancet Neurology, 18(1), 88–106. http://doi.org/10.1016/S1474-4422(18)30403-4

Olayinka, O. O., & Mbuyi, N. N. (2014). Epidemiology of dementia among the elderly in Sub-Saharan Africa. International Journal of Alzheimer’s Disease, 2014. https://doi.org/10.1155/2014/195750

Studies in Mexico have reported diabetes and hypertension as risk factors for dementia (Academia Nacional de Medicina de México, 2017).

References:

Academia Nacional de Medicina de México. (2017). La Enfermedad de Alzheimer y otras demencias como problema nacional de salud. Documento de postura (L. Robledo, Maria. Peña, Paloma. Rojas, & A. Martinez, Eds.; 1a edición). Intersistemas. https://www.anmm.org.mx/publicaciones/ultimas_publicaciones/ANM-ALZHEIMER.pdf

  • Age

In line with international research, dementia risk in South Africa was associated with older age (De Jager et al., 2017; Kalula & Petros, 2011). The landscape of age-associated risk of dementia with older age is however changing. HIV-associated dementia (HAD) is considered to be the most common cause of dementia among adults 40 years and younger (Rowland and Pedley, 2010 as in Robbins et al., 2011; Kalaria et al., 2008). Emerging research in South Africa on developing appropriate screening for HIV-associated dementia (HAD) has found that 80% of the study’s 65 participants were on average 40 years of age (range 19-68 years; SD 9.26) and screened positive for HAD (Robbins et al., 2011). Therefore, the expected risk of dementia with older age is changing with the sequelae of the high HIV/AIDS prevalence in South Africa.

  • HIV/AIDS

Depending on the progression of the disease, 30-60% of people living with HIV (PLWH) will manifest some degree of neurocognitive disturbance, whereas an estimated 50% will develop a HIV-associated neurocognitive disorder (HAND) (Fogel et al., 2014; Grant, 2008). HIV-associated dementia (HAD) is recognised as the most severe form of HAND and identified as the most common neurocognitive consequence of untreated HIV infection (Robbins et al., 2011).

In a study validating the International HIV Dementia Scale in South Africa, a sample of 96 HIV-positive individuals who are not receiving ART, displayed greater impairment on a range of neuropsychological tests (including HAD) when compared to HIV-negative controls (Joska et al., 2011). Another study examining the rates of positive HIV-associated dementia (HAD) screens at a general medical clinic in the Western Cape Region found that in a sample of 65 HIV-positive participants, 80% (n=52) were at risk for having HAD (Robbins et al., 2011). These participants have been diagnosed with the HIV virus for just over 5 years and have been on ART for more than 3 years, with less than 90% adherence. Majority of participants were female (65%) and ranged between the ages of 19 and 68 (mean 40 yrs, SD 9.26). Significant relationships were found with known associated risk factors for HAD such as low CD4 count, the presence of an alcohol disorder, and a current alcohol dependence disorder (Robbins et al., 2011). Therefore, suggesting that HIV-positive South Africans on ART, with low CD4 count and adherence issues may be at a very high risk for developing HAD.

  • Family history

The aetiology of AD/dementia are not fully understood yet; however, generic factors such as the apolipoprotein E (APOE) epsilon 4 (e4) allele) and having a family history of dementia has been linked to the development of the disease (Kowall et al., 2018; Meyer et al., 2016). It is believed that where there is a first degree relative with dementia, the risk in developing AD increases by 10-30% (Meyer et al., 2016). Genetic links to dementia in the African region is inconclusive as research in Sub-Saharan Africa on aetiology of dementia and AD has not supported these genetic associations found elsewhere (Olayinka & Mbuyi, 2016).

  • Sex

The incidence and prevalence of Alzheimer’s disease (AD) or dementia is not conclusively associated with sex, but research in developing countries suggest that it is more prone amongst women with increasing age (Kalaria et al., 2008; Meyer et al., 2016). However, the largest prevalence study in a South African rural community, to date, found no association between being female and screening positive for dementia, despite 68.6% of participants being female  (De Jager et al., 2017). Given the known increased risk with increasing age, women are more likely to develop dementia as they tend to have longer life expectancies.

  • High prevalence of stroke and associated risk factors

Stroke is a major cause of long term mortality and disability in developing countries (Kalaria et al., 2008). However, there is no compelling evidence that controlling for or modifying vascular risk factors can prevent dementia (Ramlall et al., 2013). However, clinical factors such as hypertension and cardiovascular diseases are commonly associated with dementia risk (Olayinka & Mbuyi, 2016). Although international prevalence research on developing countries suggest that vascular dementias are low, Kalula et al., (2010) found that vascular dementia (VaD) (28%) and mixed dementia (15%) had a higher prevalence in South Africa. This finding suggests that a high prevalence of stroke and associated risk factors (e.g., hypertension and cardiovascular diseases) require improved management within health care practices. A study describing the clinical and risk profile of a sample of older participants in Durban (Kwazulu-Natal) (n=140) who were assessed for dementia and mild cognitive impairment (MCI), found that vascular risk factors were most prevalent (Ramlall et al., 2013). Thirty-six point four (36.4%) percent of those who screened positive for dementia (n=38) had a history of stroke and 66.4% had hypertension (i.e. 36.7% in dementia and 57.9% in MCI) (Ramlall et al., 2013). Therefore, in the absence of specific, accessible treatment of dementia, researchers call for the optimum and aggressive management of vascular risk factors such as hypertension, diabetes, weight, and use of substances (e.g., smoking) (Ramlall et al., 2013; Wilson et al., 2011).

  • Low levels of education and literacy

Globally, as well as in Sub-Saharan Africa, low literacy levels has been identified as a risk factor for dementia (Olayinka & Mbuyi, 2016). In  certain communities in South Africa more than 80% of older persons people do not read or write (Kalaria et al., 2008). Low literacy is often linked to poverty or lower socio-economic status and therefore associated with constrained access to health care, poorer health, and increased risk of dementia (Kalaria et al., 2008). A cross-sectional community prevalence study has found a negative association between increasing education level and dementia, thus supporting the notion that formal education, cognitive reserve and resulting informed lifestyle choices, are protective against cognitive decline (De Jager et al., 2017). In fact, 69.8% of the 1394 participants had less than 7 years of education. The educational qualifications and better remuneration of caregivers in rural context in Kwazulu-Natal was also found to play a protective role in the care for persons with dementia, as it was found to guard against caregiver burden (Gurayah, 2015), and promote access to care resources.

References:

De Jager, CA, Msemburi, W., Pepper, K., & Combrinck, M. (2017). Dementia Prevalence in a Rural Region of South Africa: A Cross-Sectional Community Study. Journal of Alzheimer’s Disease, 60(3), 1087–1096. https://doi.org/10.3233/JAD-170325

Fogel, G. B., Lamers, S. L., Levine, A. J., Valdes-Sueiras, M., McGrath, M. S., Shapshak, P., & Singer, E. J. (2014). Factors related to HIV-associated neurocognitive impairment differ with age. Journal of NeuroVirology, 21(1), 56–65. https://doi.org/10.1007/s13365-014-0296-9

Grant, I. (2008). Neurocognitive disturbances in HIV. International Review of Psychiatry, 20(1), 33–47. https://doi.org/10.1080/09540260701877894

Gurayah, T. (2015). Caregiving for people with dementia in a rural context in South Africa. South African Family Practice, 57(3), 194–197. https://doi.org/10.1080/20786190.2014.976946

Joska, J., Westgarth-Taylor, J., Hoare, J., Thomas, K. G. ., Paul, R., Myer, L., & Stein, D. (2011). Validity of the International HIV Dementia Scale in South Africa. Arquivos de Neuro-Psiquiatria, 25(2), 95–101. https://doi.org/10.1089/apc.2010.0292

Kalaria, R. N., Maestre, G. E., Arizaga, R., Friedland, R. P., Galasko, D., Hall, K., Luchsinger, J. A., Ogunniyi, A., Perry, E. K., Potocnik, F., Prince, M., Stewart, R., Wimo, A., Zhang, Z. X., & Antuono, P. (2008). Alzheimer’s disease and vascular dementia in developing countries: prevalence, management, and risk factors. The Lancet Neurology, 7(9), 812–826. https://doi.org/10.1016/S1474-4422(08)70169-8

Kalula, S. Z., & Petros, G. (2011). Responses to Dementia in Less Developed Countries with a focus on South Africa. Global Aging, 7(1), 31–40.

Kalula, S. Z., Ferreira, M., Thomas, K. G. F., De Villiers, L., Joska, J. A., & Geffen, L. N. (2010). Profile and management of patients at a memory clinic. South African Medical Journal, 100(7), 449. https://doi.org/10.7196/SAMJ.3384

Kowall, N. W., Raby, B. A., & Disclosures, C. (2018). Authors: Rick Sherva, PhD, Neil W Kowall, MD Section Editors: Steven T DeKosky, MD, FAAN, FACP, FANA, Benjamin A Raby, MD, MPH Deputy Editor: Janet L Wilterdink, MD Contributor Disclosures. 1–16.

Meyer, J. C., Harirari, P., & Schellack, N. (2016). Overview of Alzheimer ’ s disease and its management. South African Pharmaceutical Journal, 83(9), 48–56.

Olayinka, O. O., & Mbuyi, N. N. (2016). Epidemiology of Dementia among the Elderly in Sub-Saharan Africa Epidemiology of Dementia among the Elderly in Sub-Saharan Africa. 2014(August 2014). https://doi.org/10.1155/2014/195750

Ramlall, S., Chipps, J., Pillay, B., & Bhigjee, A. (2013). Mild cognitive impairment and dementia in a heterogeneous elderly population: Prevalence and risk profile. African Journal of Psychiatry (South Africa), 16(6), 456–465. https://doi.org/10.4314/ajpsy.v16i6.58

Robbins, R. N., Remien, R. H., Mellins, C. A., Joska, J. A., & Stein, D. J. (2011). Screening for HIV-Associated Dementia in South Africa: Potentials and Pitfalls of Task-Shifting. AIDS Patient Care and STDs, 25(10), 587–593. https://doi.org/10.1089/apc.2011.0154

Wilson, D., Ritchie, C. W., Peters, R., & Ritchie, K. (2011). Latest advances on interventions that may prevent, delay or ameliorate dementia. Therapeutic Advances in Chronic Disease, 2(3), 161–173. https://doi.org/10.1177/2040622310397636