Prevalence of Dementia, Depression, and Mild Cognitive Impairment in a Rural Area of the Island of Crete, Greece

Abstract

The studies on the prevalence of dementia, depression, and mild cognitive impairment (MCI) in Greece are sparse and show major variations of prevalence depending on geographical areas, nutritional habits, and the way of living. The aim of this door-to-door study was to find the prevalence of dementia, depression, and MCI in a rural Greek population. Four hundred and forty-three individuals older than 61years following the application of specific criteria were diagnosed with: normal cognition, depression, MCI with and without depression, and dementia with and without depression. Four diagnostic methods were used, 2 of which included Mungas correction for age and education. After Mungas adjustment, the results were as follows—depression: 33.9%; MCI: 15.3%; MCI with depression: 8.6%; dementia: 2.0%; and dementia with depression: 7.2%. Dementia is less prevalent compared to global data and other Greek areas. Mild cognitive impairment is more prevalent than dementia. High percentages of depression may be related to low education.

Introduction

Dementia has been described as a clinical syndrome caused by neurodegeneration (Alzheimer’s disease [AD], Lewy body, and frontotemporal dementia being the most common pathologies) or a secondary syndrome (vascular, metabolic, hormonic, and infectious dementia), characterized by progressive deterioration in cognitive ability, behavior, and capacity for independent living. ¹ Typically, it is a condition that usually affects older people. ^{2 –4} Because of longer life expectancy along with the lack of efficient therapeutic strategies, dementia is increasingly becoming a major public health problem.

The number of patients with dementia has been rapidly growing in last decade. According to the latest data of the World Alzheimer’s Report 2015, there are currently 47.47 million cases and the expected numbers for 2030 and 2050 are 75.63 and 135.46 million, respectively. ⁵ The prevalence of dementia ranges from 1% in people younger than 60 years to 45% in people older than 85 years. The age-standardized prevalence of dementia for people aged ≥60 years varied between 5% and 7% in most world regions, with a higher prevalence in Latin America (8.5%), and a distinctively lower prevalence in the 4 sub-Saharan African regions (2%-4%). ¹ Demographic aging is progressing rapidly in the low- and middle-income countries (LAMICs), such as China, India, and South America, and 58% of all people with dementia live in these countries. ⁵

Mild cognitive impairment (MCI) is an intermediate state between normal cognitive aging (becoming significantly forgetful) and dementia. The construct of MCI has evolved to capture this predementia phase of cognitive dysfunction. ^6,7 Ιt was observed that people who meet the criteria for MCI are likely to progress to dementia at a rate of approximately 12% per year, compared to 1% to 2% for cognitively normal people of the same age. ^7,8 However, many people with MCI never develop dementia, and some types of MCI can be static or may in some cases revert to normal cognition. ^9,10 Recent data indicated that the percentage of patients with MCI is between 1.7% and 22.6% in Europe, America, and Brazil. ¹¹ Furthermore, the incidence (new cases in a specified period) of MCI ranges between 51 and 76.8 per 1000 person-years. ¹¹ More recent data indicated an essential variation for both incidence (MCI: 21.5-71.3 per 1000 person-years) and prevalence (MCI: 3%-42%) in North America, Europe, Africa, Asia, and Australia. ¹² To our knowledge, very few population-based studies have been published regarding LAMICs. A recent study in LAMICs regions indicated that Latin America has an amnestic MCI prevalence ranging between 3.8% and 6.3%, India has a crude amnestic MCI prevalence of 4.3%, and China has the lowest prevalence of 0.8%. ¹³

Depression is the most common comorbidity in cognitive impairment among the elderly patients. Late-life depression and cognitive impairment have become a global issue that burdens the health-care system and society. The worldwide prevalence of late-life depression was estimated to range from 3% to 30% ¹⁴ and is consistently associated with an increased risk of dementia and particular in AD and vascular dementia. ^{15 –18} However, it remains unclear whether a history of depression is a true risk factor for dementia or rather represents a prodromal clinical phase of the neurodegenerative changes that occur in AD. Depression may be a psychological response to AD or an outcome of the same pathogenic process that lead to the other symptoms of AD (eg, aberrant amyloid-β processing, tau hyperphosphorylation, etc). ¹⁹ Furthermore, it has been reported the potential role of depression in the conversion from normal cognition to MCI and from MCI to dementia. ^{20 –24} Although late-onset depression increases the risk of progression to MCI, chronic depression is associated with only a modest increase in the risk of MCI to AD transition. ²⁵

The studies on the prevalence of dementia and MCI in Southern Europe, ^{26 –28} and Greece, in particular, are sparse. ^{29 –31} However, the prevalence of depression or its relation with cognitive decline has examined extensively in Greek area. ^{31 –36} The aim of this study is to examine the prevalence of cognitive impairment and depression symptoms in a rural Greek population, residing on the island of Crete, the birthplace of Mediterranean diet. We thus seek to estimate the prevalence of (a) normal mental status, (b) depression, (c) dementia with depressive symptoms, (d) dementia without depressive symptoms, (e) MCI with depressive symptoms, and (f) MCI without depressive symptoms.

Materials and Methods

Study Design

This is a door-to-door, home-based questionnaire-type study. It began in July 2006 and ended in January 2007.

Setting Participants

The municipality of Milopotamos is a rural area close to Heraklion, the largest city of Crete. Milopotamos comprises 8 villages whose residents older than 65 years were 1726 according to the municipality data. Some of the residents (468 people) were not tracked, others (170 people) denied to participate in the study, and another 546 people had moved out of the villages and could not be detected, whereas some of them (99 people) were unable to answer the questionnaire or answer some of the questions. This is a not surprising condition due to the population targeted: Elderly patients with low levels of education, often suspicious, reserved and with limited exposure to and familiarity with voluntary participation in research. Finally, 443 residents participated in this study.

Study Procedure

This study was carried out by 2 research assistants, students of the Department of Social Work, Crete, and a group of students of the Department of Social Work after intensive training by a neuropsychologist and a social worker, in collaboration with a neurologist, specialist in dementia, and who is working at the Third Department of Neurology at the Aristotle University of Thessaloniki. The census lists of Milopotamos residents were obtained from the municipality registry office. All municipality-registered residents aged 65 and older were eligible for the study. First, we contacted the mayor of the municipality of Milopotamos, in order to request permission for our research and seek support if required. The study protocol was explained and discussed in meetings with general practitioners, local health authorities, and the residents. We also contacted authorities (presidents, priests, and rural doctors) of each village requesting their assistance in raising awareness concerning dementia among residents. We would not have found the addresses of the residents without the precious help of the municipality employees. All participants were assessed in person at their residence by the research assistants and students who were well trained in completing the questionnaires. Initially, a questionnaire on demographics was administered, whose items concerned age, gender, education, occupation, marital status, health problems (illness, medication), self-care, use of leisure time, lifestyle habits (smoking, alcohol use, exercise), and awareness/perceptions about AD. Subsequently, the neuropsychological battery described below was administered and recorded. The scores and results were forwarded to the neurology specialist in dementia, who interpreted test scores according to established cutoffs and was responsible for the final diagnosis.

Ethical Considerations

The study protocol was approved by the research ethics committee of the School of Health and Welfare Services of the Technological Educational Institute of Crete and was made in accordance with the ethical standards of the Institute and the guidelines outlined in the Declaration of Helsinki. ³⁷ The researchers informed the participants of the study procedures and discussed thoroughly different areas of concern, including data protection. Patients who agreed to participate in the study signed the informed consent document and were provided with the researchers’ contact details.

Neuropsychological Assessment

A neuropsychological test battery was administrated in order to evaluate not only the participants’ cognitive and mood status but also activities of daily living. This battery includes the Mini–Mental State Examination (MMSE) or the Hindi Mental State Examination for illiterates (Hindi), the Instrumental Activity of Daily Living (IADL), and the Geriatric Depression Scale (GDS). In our study, the Greek version of MMSE ³⁸ was administered to people who had completed at least 5 years of basic education. In those with fewer years of education, we used the Hindi test instead. ³⁹ The IADL is an old test which describes instrumental tasks in a person’s everyday life and is used to assess the functional status: using the telephone, going shopping, preparing own meals, doing housework, laundering, using transportation, managing medicine, and handling money. However, in our study, we only used the question items which assessed the ability to use the telephone, transportation, medication, and financial behavior. The choice of these question items was based on the assumption that the male population in Greece is not usually involved in housework. ^40,41 The short form of the GDS with 15 closed questions was also used in order to assess the mood and the emotions of the elderly patients. Scores between 0 and 6 are considered normal while scores between 7 and 15 indicate depressive symptoms. ⁴²

Diagnosis

The participants of our study were divided into 6 groups according to appropriate criteria—(1) normal mental status, (2) depressive symptoms, (3) MCI with depressive symptoms, (4) MCI without depressive symptoms, (5) dementia with depressive symptoms, and (6) dementia without depressive symptoms. We used 4 methods of diagnosis in order to compare the prevalence in each of them and discuss their methodological value.

In method 1, the participants were divided into groups based on the MMSE/HINDI and GDS scores. The MMSE/HINDI score for MCI was less than 28 and greater than 24. In MCI without depressive symptoms, the GDS score was less than 6, and for MCI with depressive symptoms, the GDS score was greater than 6. We used the Diagnostic and Statistical Manual of Mental Disorder, Fourth Edition (DSM-IV) criteria ⁴³ for depression diagnosis (MMSE/HINDI score >28), with a GDS score greater than 6. The DSM-IV dementia criteria were applied when the MMSE/HINDI score was less than 24. For dementia without depressive symptoms, the GDS score was lower than 6, and for dementia with depressive symptoms, the GDS score was greater than 6. Finally, in normal mental status diagnosis, group had MMSE/HINDI over 28 and GDS lower than 6.

In method 2, the participants were divided according to first diagnosis criteria plus the Mungas adjustment (MMSEadj), ⁴⁴ a correction of MMSE/HINDI for age and education. In method 3, we used Petersen criteria ⁴⁵ for MCI diagnosis with MMSE/HINDI score less than 28 and greater than 24 with no functional impairment according to the IADL scale: All IADL item respondents showed the ability to perform tasks independently or with some help. Besides, GDS score was less than 6 for MCI without depressive symptoms and greater than 6 in MCI with depressive symptoms. We used the DSM-IV criteria ⁴³ for depression diagnosis, with an MMSE/HINDI score greater than 28, no functional problems, or if any they were due to coexisting health problems. In all these participants, the GDS score was greater than 6. Dementia diagnosis was based on the DSM-IV criteria and MMSE/HINDI score was less than 24. For dementia without depression, the GDS score was less than 6 and there were functional problems as well. For dementia with depression, the GDS score was greater than 6 with functional problems as well. Apart from the appliance of diagnostic criteria and neuropsychological tools (MMSE/Hindi, IADL, and GDS) for establishing the diagnosis, we collected information about factors such as the age, gender, current employment, marital status, health problems, and way of living of all participants. Finally, respondents not included in any of the above categories were of normal mental status: They had high score on the MMSE/HINDI (>28), no functional problems, and no depression symptoms.

Method 4 was based on method 3 criteria plus the MMSEadj.

Statistical Analysis

The raw prevalence of each diagnostic category was calculated with respect to the total sample of the study. Raw prevalence and prevalence after MMSEadj were calculated according to age group and gender.

Mungas correction was introduced by Mungas et al in 1996. ⁴⁴ The authors claimed the MMSE may be biased against MCI and dementia due to demographic value effects, such as age and education. Consequently, Mungas is a safe measure of cognitive state in low educated people. Ιts mathematical operations contributed to the greater sensitivity and specificity of the MMSE test. The Mungas formula, providing an adjustment for age and education for the raw MMSE score, is given as follows:

$$\text{MMSEadj}=\text{RawMMSE}-(0.471\times [\text{education}-12])+(0.131\times [\text{age}-70]).$$

For each prevalence estimate, 95% confidence intervals (95% CIs) were also calculated. Continuous variables were presented as mean value (SD) and compared using Student t test between groups. One-way analysis of variance with Bonferroni post hoc tests was used to check differences between means of continuous variables for the different diagnostic groups. Pearson χ² test was used to check the independence between categorical variables. P values <.05 were considered statistically significant. Statistical analysis was performed using SPSS v21.0 (IBM Corp, Armonk, New York).

Results

A total of 443 patients were included in the study with 49.7% of those being females. Considering each diagnosis separately for the raw data and according to method 4, the percentage of females in the normal group (N = 146) was 32.2%. In the depression group (N = 150), the female percentage was 62.7%, in the MCI group (N = 68) 35.3%, in the MCI with depression group (N = 38) 73.7%, for the dementia group (N = 9) 55.6%, and in the dementia with depression group (N = 32), the female percentage was 68.8%.

Frequencies and relative frequencies of each diagnosis status for the raw data before and after MMSEadj are shown in Table 1 and Figure 1. There is an association between the diagnosis and the method used (χ² = 228.97, degrees of freedom [df] = 15, P < .001). There are more individuals in the normal and depression groups after applying MMSEadj.

Table 1.

Frequencies and Relative Frequencies of the Sample for Each Diagnosis for the Raw Data of Methods 1, 2, 3, and 4.

Diagnosis	Method 1, n (%)	Method 2, n (%)	Method 3, n (%)	Method 4, n (%)
Normal	109 (24.6)	186 (42.0)	99 (22.3)	146 (33.0)
Depression	94 (21.2)	157 (35.4)	61 (13.8)	150 (33.9)
MCI without depression	73 (16.5)	26 (5.9)	89 (20.1)	68 (15.3)
MCI with depression	57 (12.9)	28 (6.3)	97 (21.9)	38 (8.6)
Dementia without depression	41 (9.3)	11 (2.5)	35 (7.9)	9 (2.0)
Dementia with depression	69 (15.6)	35 (7.9)	62 (14.0)	32 (7.2)

Abbreviation: MCI, mild cognitive impairment.

Figure 1.

Prevalence of each diagnosis for the 4 different methods.

The mean age of all participants was 75.3 (7.1) and the mean years of education were 3.5 (2.7). There was no difference in age between males and females (P = .347). However, females had significantly fewer years of education (2.7 (2.4)) than males (4.3 (2.9); t[441] = 6.321; P < .001).

Age and Education in Diagnosis Prevalence

Table 2 shows the age and education characteristics according to method 4 of the total data set for males, females, and both. Table 2 also shows the group comparison concerning age and education in the normal group (p1) as well as the comparison between genders (p2).

Table 2.

Age and Education Characteristics According to Sex and Diagnosis for Method 4.^a

	Males	Females	Both	p1	p2
Age
Normal (n = 146)	73.2 (7.1)	72.7 (6.0)	73.0 (6.8)		0.711
Depression (n = 150)	75.4 (6.9)	75.9 (7.3)	75.7 (7.1)	0.001	0.705
MCI without depression (n = 68)	76.6 (5.1)	74.9 (8.3)	76.1 (6.4)	0.003	0.299
MCI with depression (n = 38)	75.3 (6.5)	78.7 (7.1)	77.8 (7.0)	<0.001	0.192
Dementia without depression (n = 9)	70.5 (4.5)	79.8 (5.8)	75.7 (6.9)	0.268	0.034
Dementia with depression (n = 32)	78.3 (7.9)	78.4 (7.6)	78.4 (7.7)	<0.001	0.958
Education
Normal (n = 146)	4.7 (3.1)	2.6 (1.9)	4.1 (2.9)		<0.001
Depression (n = 150)	3.9 (2.4)	1.9 (2.0)	2.7 (2.4)	<0.001	<0.001
MCI without depression (n = 68)	3.9 (2.4)	3.4 (3.0)	3.8 (2.9)	0.484	0.446
MCI with depression (n = 38)	3.8 (2.4)	4.0 (2.8)	3.9 (2.7)	0.826	0.844
Dementia without depression (n = 9)	7.5 (3.0)	3.0 (2.4)	5.0 (3.5)	0.304	0.042
Dementia with depression (n = 32)	2.0 (1.3)	3.7 (2.1)	3.2 (2.0)	0.086	0.028

Abbreviation: MCI, mild cognitive impairment.

^ap1 is difference from normal and p2 is difference between males and females.

Gender and Age in Diagnosis Prevalence

Gender

There is a correlation between diagnosis and gender. Females have more depressive symptoms than males. This result was the same for method 1 (Pearson χ² = 59.94, df = 5, P < .001), method 2 (Pearson χ² = 49.10, df = 5, P < .001), method 3 (Pearson χ² = 63.28, df = 5, P < .001), and method 4 (Pearson χ² = 47.89, df = 5, P < .001; Table 3).

Table 3.

Gender Prevalence of Diagnosis of the Total Sample in Methods 1, 2, 3, and 4.

Age Groups	Male				Female
Diagnosis	1	2	3	4	1	2	3	4
Normal
61-70	42 (56.0)	47 (62.7)	40 (53.3)	43 (57.3)	14 (21.5)	23 (35.4)	13 (20.0)	20 (30.8)
71-80	33 (30.6)	63 (58.3)	29 (26.9)	41 (38.0)	12 (12.2)	29 (29.6)	9 (9.2)	23 (23.5)
81-90	8 (22.9)	15 (42.9)	8 (22.9)	13 (37.1)	0 (0.0)	6 (12.0)	0 (0.0)	4 (8.0)
91+	0 (0.0)	3 (60.0)	0 (0.0)	2 (40.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)
P	0.373				0.338
Depression
61-70	15 (20.0)	17 (22.7)	12 (16.0)	17 (22.7)	16 (24.6)	26 (40.0)	12 (18.5)	26 (40.0)
71-80	19 (17.6)	28 (25.9)	15 (13.9)	26 (24.1)	22 (22.4)	46 (46.9)	13 (13.3)	43 (43.9)
81-90	7 (20.0)	12 (34.3)	3 (8.6)	12 (34.3)	13 (26.0)	22 (44.0)	5 (10.0)	21 (42.0)
91+	1 (20.0)	1 (20.0)	0 (0.0)	1 (20.0)	1 (14.3)	5 (71.4)	1 (14.3)	4 (57.1)
P	0.95				0.956
MCI without depression
61-70	6 (8.0)	2 (2.7)	7 (9.3)	6 (8.0)	10 (15.4)	4 (6.2)	14 (18.4)	8 (12.3)
71-80	30 (27.8)	10 (9.7)	31 (28.7)	32 (29.6)	17 (17.3)	6 (6.1)	23 (23.5)	12 (12.2)
81-90	7 (20.0)	2 (5.7)	7 (20.0)	5 (14.3)	3 (6.0)	1 (2.0)	5 (10.0)	3 (6.0)
91+	0 (0.0)	0 (0.0)	2 (40.0)	1 (20.0)	0 (0.0)	1 (14.3)	0 (0.0)	1 (14.3)
P a	0.977				0.827
MCI with depression
61-70	4 (5.3)	3 (4.0)	6 (8.0)	3 (4.0)	13 (20.0)	4 (6.2)	18 (27.7)	5 (7.7)
71-80	7 (6.5)	2 (1.9)	11 (10.2)	5 (4.6)	20 (20.4)	9 (9.2)	32 (32.7)	12 (12.2)
81-90	5 (14.3)	2 (5.7)	9 (25.7)	2 (5.7)	6 (12.0)	7 (14.0)	17 (34.0)	9 (18.0)
91+	0 (0.0)	0 (0.0)	1 (20.0)	0 (0.0)	2 (28.6)	1 (14.3)	3 (42.9)	2 (28.6)
P	0.961				0.825
Dementia without depression
61-70	4 (5.3)	3 (4.0)	5 (6.7)	3 (4.0)	4 (6.2)	1 (1.5)	1 (1.5)	0 (0.0)
71-80	11 (10.2)	1 (0.9)	14 (13.0)	1 (0.9)	9 (9.2)	3 (3.1)	6 (6.1)	3 (3.1)
81-90	3 (8.6)	1 (2.9)	3 (8.6)	0 (0.0)	6 (12.0)	2 (4.0)	4 (8.0)	2 (4.0)
91+	3 (60.0)	0 (0.0)	1 (20.0)	0 (0.0)	1 (14.3)	0 (0.0)	1 (14.3)	0 (0.0)
P	0.294				0.975
Dementia with depression
61-70	4 (5.3)	3 (4.0)	5 (6.7)	3 (4.0)	8 (12.3)	7 (10.8)	7 (10.8)	6 (9.2)
71-80	8 (7.4)	4 (3.7)	8 (7.4)	3 (2.8)	18 (18.4)	5 (5.1)	15 (15.3)	5 (5.1)
81-90	5 (14.3)	3 (8.6)	5 (14.3)	3 (8.6)	22 (44.0)	12 (24.0)	19 (38.0)	11 (22.0)
91+	1 (20.0)	1 (20.0)	1 (20.0)	1 (20.0)	3 (42.9)	0 (0.0)	2 (28.6)	0 (0.0)
P	1				0.637

Abbreviation: MCI, mild cognitive impairment.

^aThe alpha level is equal to 0.05.

Age

There were no significant differences between the prevalence of method 1, the prevalence of method 2, and the prevalence coming from methods 3 and 4. A possible explanation may be the participants’ poor schooling.

The prevalence of method 4 in the “normal” group was 45% (95% CI [36.8-53.2]) for the 61- to 70-year-old individuals, 31.1% (95% CI [24.8-37.4]) for the 71- to 80-year-old ones, and 20.0% (95% CI [11.5-28.5]) for the 81- to 90-year-old individuals. As people grow older, cognitive impairment and mood disorders are more possible.

The prevalence of “depression” was 30.7% (95% CI [23.1-38.3]) in the 61- to 70-year-old group, 33.5% (95% CI [27.1-39.9]) in the 71- to 80-year-old group, 38.8% (95% CI [28.4-49.2]) in the 81- to 90-year-old group, and 41.5% (95% CI [13.6-69.4]) in the 91+ year-old ones. Depression diagnosis is more prevalent in older ages.

The highest prevalence of “MCI without depressive symptoms” appeared to be in the 71- to 80-year-old group, which was 21.4% (95% CI [15.8-27.0]). The other groups had lower percentages. More specifically, in the 61- to 70-year-old group, the prevalence was 10.0% (95% CI [5.0-15.0]), in the 81- to 90-year-old group was 9.4% (95% CI [0.0, 15.6]), and in the 91+ year-old group was 16.7% (95% CI [0.0-37.8]).

The highest prevalence “MCI with depressive symptoms” appeared to be in the 91+ year-old individuals and was equal to 16.7% (95% CI [0.0-37.8]). Then, in the 81- to 90-year-old group, the prevalence was 12.9% (95% CI [5.8-20.0]). In the 71- to 80-year-old group, the prevalence was 8.3% (95% CI [4.5-12.1]) and in the 61- to 70-year-old group was 5.7% (95% CI [0.0-9.5]). The youngest group had the lowest prevalence of MCI with depressive symptoms.

The highest prevalence of “dementia without depressive symptoms” was found in the 81- to 90-year-old individuals and was equal to 2.4% (95% CI [0.0-5.7]), and the lowest prevalence was found in the 91+ year-old group and was equal to 0.0% (95% CI [0.0-0.0]). Moreover, in the 71- to 80-year-old group, the prevalence was 1.9% (95% CI [0.0-3.8]), whereas in the61- to 70-year-old group, the prevalence was 2.1% (95% CI [−0.3 to 4.5]).

The highest prevalence of “dementia with depressive symptoms” appeared in the 81- to 90-year-old group and was equal to 16.5% (95% CI [8.6-24.4]) and then in the 91+year-old group which was 8.3% (95% CI [0.0-23.9]). The rest of age groups had lower prevalence. In the 71- to 80-year-old group, the prevalence was 3.9% (95% CI [1.3-6.5]) and in the 61- to 70-year-old group was 6.4% (95% CI [2.3-10.5]; Table 4 and Figure 2).

Table 4.

Age Prevalence of Diagnosis of the Total Sample in Methods 1, 2, 3, and 4.

Age Groups Both	Age Groups Both	Age Groups Both	Age Groups Both	Age Groups Both
Diagnosis	1	2	3	4
Normal
61-70	56 (40.0)	70 (50.0)	53 (37.9)	63 (45.0)
71-80	45 (21.8)	92 (44.7)	38 (18.4)	64 (31.1)
81-90	8 (9.4)	21 (24.7)	8 (9.4)	17 (20.0)
91+	0 (0.0)	3 (25.0)	0 (0.0)	2 (16.7)
P	.207
Depression
61-70	31 (22.1)	43 (30.7)	24 (17.1)	43 (30.7)
71-80	41 (19.9)	74 (35.9)	28 (13.6)	69 (33.5)
81-90	20 (23.5)	34 (40.0)	8 (9.4)	33 (38.8)
91+	2 (16.7)	6 (50.0)	1 (8.3)	5 (41.5)
P	.789
MCI without depression
61-70	16 (11.4)	6 (4.3)	21 (15.0)	14 (10.0)
71-80	47 (22.8)	16 (7.8)	54 (26.2)	44 (21.4)
81-90	10 (11.8)	3 (3.5)	12 (14.1)	8 (9.4)
91+	0 (0.0)	1 (8.3)	2 (16.7)	2 (16.7)
P	.973
MCI with depression
61-70	17 (12.1)	7 (5.0)	24 (17.1)	8 (5.7)
71-80	27 (13.1)	11 (5.3)	43 (20.9)	17 (8.3)
81-90	11 (12.9)	9 (10.6)	26 (30.6)	11 (12.9)
91+	2 (16.7)	1 (8.3)	4 (33.3)	2 (16.7)
P	.973
Dementia without depression
61-70	8 (5.7)	4 (2.9)	6 (4.3)	3 (2.1)
71-80	20 (9.7)	4 (1.9)	20 (9.7)	4 (1.9)
81-90	9 (10.6)	3 (3.5)	7 (8.2)	2 (2.4)
91+	4 (33.3)	0 (0.0)	2 (16.7)	0 (0.0)
P	.819
Dementia with depression
61-70	12 (8.6)	10 (7.1)	12 (8.6)	9 (6.4)
71-80	26 (12.6)	9 (4.4)	23 (11.2)	8 (3.9)
81-90	27 (31.8)	15 (17.6)	24 (28.2)	14 (16.5)
91+	4 (33.3)	1 (8.3)	3 (25.0)	1 (8.3)
P	.845

Abbreviation: MCI, mild cognitive impairment.

Figure 2.

Prevalence of each diagnosis for method 4 for the different age categories.

Discussion

Our study population eventually consisted of 443 residents from a mountainous area of Heraklion, in Crete. Prevalence varied depending on the diagnostic method we used. Some studies have indicated that the adjusted MMSE has higher sensitivity and specificity than the unadjusted MMSE. ^44,46,47 The MMSEadj, used in methods 2 and 4 was compared to the raw MMSE scores in methods 1 and 3 of each diagnosis (Table 1). An interesting finding was that the means of MMSE and GDS scores were higher in normal, depression, MCI, and MCI with depressive symptoms diagnosis after MMSEadj (Table 5). Furthermore, there was a higher prevalence in normal and depression groups and a lower prevalence in the “MCI” and “dementia” groups, after applying the MMSEadj (Table 1). We conclude that after adjusting for age and education, individual cognitive deficits fall within the range of normal or depression. Furthermore, in our findings, methods 3 and 4 of diagnosis were based not only on mental and cognitive state tests (as methods 1 and 2) but also on functionality in a daily life test. Due to the fact that functionality (as measured with IADL tool) is a diagnostic criterion of dementia and MCI and that MMSEadj corrects age and education differences, we took into consideration the raw scores of method 4 of each diagnosis as the most appropriate method to discuss prevalence (Table 6).

Table 5.

MMSE and GDS Scoring Per Diagnosis for the Sample Before and After Mungas Adjustment.

Diagnosis	MMSE (Mean (SD))	GDS (Mean (SD))
Before Mungas adjustment
Normal	29.09 (0.52)	2.47 (1.58)
Depression	29.11 (0.32)	8.43 (1.85)
MCI	25.48 (2.31)	2.92 (1.64)
MCI + depression	25.96 (2.61)	8.93 (2.33)
Dementia	20.31 (4.74)	2.97 (1.60)
Dementia + depression	18.15 (4.90)	9.45 (2.22)
After Mungas adjustment
Normal	29.81 (0.53)	2.63 (1.57)
Depression	29.84 (0.41)	8.70 (2.07)
MCI	28.06 (2.30)	2.97 (1.68)
MCI + depression	26.45 (1.90)	9.39 (2.57)
Dementia	18.59 (4.96)	2.56 (1.81)
Dementia + depression	19.74 (3.38)	9.50 (2.20)

Abbreviations: MMSE, Mini–Mental State Examination; GDS, Geriatric Depression Scale; MCI, mild cognitive impairment; SD, standard deviation.

Table 6.

Plos and Cons for Each of 4 Diagnosis Method.

Diagnosis Methods	1	2	3	4
Pros	(1) Direct administration for assessing cognitive status and mood behavior, without needing the relatives presence	(1) Direct administration for assessing cognitive status and mood behavior, without needing the relatives presence	(1) A well-established diagnosis with functional criteria	(1) A well-established diagnosis with functional criteria
		(2) Adjustment for age and education		(2) Adjustment for age and education
Cons	(1) No data regarding the functionality	(1) No data regarding the functionality	(1) Missing the adjustment of age and education	–
	(2) Missing the adjustment for age and education

Summarizing our main findings, people are more likely to develop dementia and MCI with or without depressive symptom as they grow older. These data are consistent with previous studies arguing that dementia affects older people. ^1,2 The unique Cretan nutritional habits may account for the low percentages of dementia in our study. In specific, the prevalence of dementia (with and without depression) according to method 4 appeared to be 9.2%. In a similar study population with Polish participants (55-104 years old), the prevalence of dementia after Mungas correction was 12.1%, a percentage much higher than ours. ⁴⁷ A possible explanation may be the different methodology of studies and different cultures, including Mediterranean nutrition of Cretan residents. The prevalence of MCI (with and without depression) was 23.9% and the prevalence of depression was 33.9%, whereas in the normal groups was 33% with adjustment.

Prevalence of Depressive Symptoms in Normal Cognition, Dementia, and MCI

A significant finding of this study was the increased proportion of individuals with depressive symptoms in all age groups (33.9%). The high prevalence of depressive symptoms in all age group of our study may be not only due to the participants’ low education (3.5 years (2.7)) but also to the restrictive way of living in a village. The indicator of lower education is associated with both odds of dementia and substantial depressive symptoms or with late-life depression, which is in agreement with the findings of other studies. ^{48 –50} Besides, in our results, lower education seems to be positively related with depression, whereas higher education seems to be a protective factor for depression, MCI, dementia, and dementia and depressive symptoms. The age groups with the highest prevalence of dementia with depressive symptoms were the 81- to 90-year-old group (16.5%). We could hence conclude that depressive symptoms are more likely to coexist with dementia as age increases. Although this finding comes in agreement with many studies, it is substantial lower than in others. In a Canadian Community Health Survey, depression seems highly prevalent (18%-28%) in neurological conditions such as AD/dementia, dystonia, multiple sclerosis, Parkinson disease, stroke, migraine, epilepsy, and spina bifida. ⁵¹ Other studies in China and Australia indicate that the prevalence of AD with depression ranges from 25% to 74.9%. ^52,53 Moreover, the higher level of depressive symptoms in AD diagnosis was associated with worse clinical outcome such as faster subsequent cognitive and functional decline. ⁵⁴ Also, findings from a study across 8 Europeans countries with severe demented participants indicated that 30% of the sample had depression. ⁵⁵

Furthermore, MCI with depressive symptoms prevailed in the 91+ year-old group (16.7%) rather than in the 81- to 90-year-old one (12.9%). Nonetheless, we need to highlight the fact that the number of participants in the 91+ group was very small, only 12 participants, so there is a limitation in our conclusions. These data confirm that depression may lead to or coexist not only with dementia but also with MCI as individuals grow older. Little is known about the prevalence of depressive symptoms in MCI by other studies. Individuals with MCI, especially aMCI, present with more depressive symptoms than the cognitively normal individuals. ⁵⁶ Another recent systematic review showed that 20% of patients with MCI aged 55 years and older seem to suffer from minor depression. ⁵⁷ Besides, very recent data provided evidence that depressive symptoms may accelerate the risk of developing dementia in patients with MCI and after 24 months of a follow-up assessment, 2% of participants developed dementia. ^58,59 These findings highlight the importance of assessing and treating depressive symptoms in MCI. ⁵⁶ Nevertheless, a recent meta-analysis stressed that it is unclear whether depressive symptoms is a risk factor for progressing dementia or whether it is an early biomarker which indicates the development of depressive symptomatology in the prodromal stages of the disease. ¹⁵ Interestingly, depression, dementia, and MCI share some common pathological features. There are demonstrated links between the development of depression and increased cerebral atrophy, neuroinflammation, oxidative stress, white matter lesions, ⁶⁰ and vascular changes in the brain. ^61,15 Given that these pathological changes are common in depression, dementia, and MCI as a predementia phase, there is a mediating neurobiological mechanism linking them. ⁶²

Prevalence in Dementia

The prevalence of dementia varies around the world, depending on cultural and socioeconomic differences among nations. In the United States, the prevalence of dementia among 856 individuals aged 71 and older was 13.9% in 2002, whereas a recent study in 2010 with 856 individuals older than 70 years indicated 14.7% which is higher than ours (9.2%), probably due to the different methodology. ^63,64 A recent review in China, which included 89 studies and 340 247 participants, indicated that the prevalence of dementia in 2010 was 2.6% for the 65- to 69-year age group and 60.5% for the 95- to 99-year age group, ⁶⁵ a percentage quite different from our findings for the 61- to 70-year age group (8.5%). Another study by Suh and Kee in 2010 showed that the prevalence of people with dementia older than 65 years in Korea, China, Taiwan, Singapore, and Japan varied between 9.7% and 14.3%, a percentage quite similar to our findings (9.2%). Overall prevalence rates in Japan and Singapore were significantly lower than those in Korea, China, and Taiwan. Prevalence rates in older groups (aged 75 and older) were markedly higher than those in younger groups (aged 65-74). ⁶⁶ The studies in Africa, especially in the sub-Saharan regions, are very sparse. An early study with 2494 participants >65 years old, divided into 2 groups of Africans (African Americans and African Nigerians) in 1995, showed that the rates of dementia were 2.29% with a lower proportion for African Nigerians. ⁶⁷ More recently in 2013, Prince and colleagues, having used meta-analysis, showed that the prevalence in this area seems to be around the same percentages (2.07%). ¹ However, Ramlall and colleagues in 2013 presented a much higher percentage of dementia prevalence (7.9%) in South Africa, but the sample was too small (N = 140). ⁶⁸ In our view of 14 selected studies from 1988 to 2001 and over 600 participants in each study, the crude prevalence rates of dementia in Europe varied between 5.9% and 9.4% for individuals aged 65 years and older, ⁶⁹ a range that includes our percentage (9.2%). Another study by Lobo and colleagues in 2000, with 2346 participants aged 65 years and older, showed that the prevalence of dementia in Europe was 6.4%. ⁷⁰ According to a EUROcODE report in 2006, the European rate of dementia prevalence is 7.1%, with Spain (16.3%, Ν = 1460), Germany (17.4%), France (17.8%), Italy (21.9%), and Sweden (13%) featuring the highest percentages. ⁷¹ Nevertheless, in the same report, there are studies with very different results in prevalence such as Spain (9.4%, N = 1954) and Italy (6.5%, N = 7930; 9.8%, N = 968). Limitations in methodology among studies are a possible reason for the lower or the higher prevalence in these areas. Low percentages of dementia recurred in a recent study of an urban Spanish region in 2011 (4.3%, Ν = 480), in line with previous studies, ⁷² whereas in Portugal, the percentage for 2010 was 2.7%. ⁷³ According to the latest data of 2015, the proportion of new cases of dementia in Europe has dropped, and the crude prevalence is 5.9% with Western Europe featuring the highest prevalence (6.9%). ⁵

Prevalence in MCI

Worldwide findings indicate that the MCI prevalence ranged between 3% and 42% in Europe, the United States, Asia, Australia, and Africa from 1984 to 2008. Specifically, the prevalence of MCI participants older than 60 years in Europe was 42.9%, 1.4% in North America, 17.1% in Asia, 5.7% in Australia, and 2.9% in Africa. According to the latest data, the MCI prevalence ranges between 5.0% and 36.7% in the United States, Europe, Asia, and Australia, ⁷⁴ that is compatible with our findings (23.9%). An early study showed that the prevalence of MCI in individuals aged 65 years and older was 28.3% in an urban community of the United States. ⁷⁵ A few years later, another study by Plassman and colleagues corroborated this prevalence in the entire United States (22.2%), a percentage lower than ours. ⁷⁶ Nevertheless, in 2012, the prevalence of people older than 60 years with MCI in the southern regions of the United States and Mexico appeared to be much lower (6.45%) probably because of the different culture and different education. ⁷⁷ Moreover, in a recent meta-analysis, it was shown that the prevalence of people older than 60 years with MCI in China was 12.7%, ⁷⁸ a percentage much lower than ours (23.9%), with Eastern China reaching 9.6% and Western China 14.7%. Poor education seems to be a catalytic factor for the high prevalence in Western China. Additionally, there seems to be a different prevalence depending on the residing area (rural vs urban) of Chinese people. The prevalence of people older than 65 years with MCI in Japan seems to be quite higher 18.8%. ⁷⁹ Then, the prevalence of MCI participants older than 65 years in Korea was 32.9% in an earlier study, a higher percentage than ours. ⁸⁰ In North India, the percentages are much higher, with the prevalence of dementia reaching 19.26%, ⁸¹ whereas in the region of Kolkata (India), the percentages of MCI prevalence seem to be much lower (6%). ⁸² Studies in Southern Europe and Mediterranean countries are of particular interest to our study. In Bulgaria, in MCI participants older than 65 years, the prevalence was found to be 6.7%. ⁸³ In Italy, MCI prevalence for people older than 60 years was 6%. ⁸⁴ In Spain, MCI prevalence ranged between 13.8% and 35.2%. ⁸⁵ However, the prevalence of MCI found in our study is lower than the one reported for participants older than 65 years with MCI in France (42%), possibly because of the much lower means of schooling years in education (for men: odds ratio [OR] = 2.3, 95% CI [1.3-4.1] and women: OR = 2.2, 95% CI [1.3-3.6]). ^86,37

Few studies have been conducted in Greece concerning the prevalence of dementia and MCI. In a study at a rural area of Northern Greece, called M. Alexandros, the prevalence of MCI according to the age groups was 1.6% for the 65- to 69-year age group, 1.7% for the 70- to 74-year age group, 4.3% for the 75- to 79-year age group, and 2.7% for those aged 80+ group. ³⁰ In the same study, the prevalence of MCI due to depression was 8.8%, a percentage similar to ours (8.6%), and 5.9% had only depression, a percentage much lower than ours (33.9%). A previous study in the municipality of Pylaia, an urban area in Thessaloniki, had indicated higher numbers of prevalence of dementia: 4.24% for the 70- to 74-year age group, 10.7% for the 75- to 79-year age group, 10.64% for the 80- to 84-year age group, 11.8% for the 85- to 89-year age group, and 36.7% for those aged 90+ group (Figure 3). ²⁹ The urban versus rural way of living may account for the difference in findings between the latter study and the present one. Moreover, the application of Mungas correction in the present study and its absence in the previous one might explain the different findings. Another study from the Northern Greece showed that 37.6% of the men and 41.6% of the women had cognitive impairment. ³¹

Figure 3.

Prevalence of dementia in Crete according to method 3 related to those in Pylea and M. Alexandros.

Despite the fact that there only few studies in cognitive impairment and depressive symptoms, several studies about prevalence in depression have been conducted in Greece area. In a rural area, Velestino, the prevalence of mild depression in late life was higher (27%) and much lower (12%) in moderate to severe depression than in our study. ³⁴ Besides, a recent study in Ikaria island, which is reported to be 1 of the places where people have the highest life expectancies in the world, indicates a very low prevalence of depression. ³⁶ Thus, elders in Ikaria have much lower rates in depressive symptoms as compared with their peers from the other Greek islands or Cyprus ⁸⁷ (in Cyprus, 25% of elderly men and 35% of elderly women had severe depressive symptoms, whereas 54% of men and 70% had mild depressive symptoms). Few years ago, another study in Athens indicated a quite high prevalence of depressed mood (27.1%) but only a 9.5% have clinical types of depression. ³² Another study in Athens indicated that 29.9% of the women and 19.6% of the men had mild to moderate depression, ³¹ a percentage higher than ours. ³¹ To our knowledge, this is 1 of the few studies in Greece which has attempted to make direct comparisons of prevalence estimates of dementia and MCI taking into consideration the cultural background and the nutritional habits of the participants. The Mediterranean diet is based on olive oil, fruit, vegetables, and fish. There are worldwide studies investigating the association between the Mediterranean diet and a slower cognitive decline. ^88,89

Conclusion

Our aim was to demonstrate the prevalence of depression, MCI, and dementia in a small area in Crete island, Greece. We used 4 different methods to establish the diagnosis. We suggest that functionality in daily life and adjustment for education and age in MMSE score are the appropriate criteria to establish a dementia diagnosis. After Mungas correction, there was a high prevalence in normal and depression groups and a lower prevalence in the MCI and dementia groups. We conclude that after adjusting for age and education, individuals’ cognitive deficits fall within the range of normal or depression.

Study Limitations

This is not a clinical study and there were no laboratory results or neuroimaging data to analyze. Therefore, it was impossible to discriminate the type of dementia for each participant. Besides, this is a nonblinding study procedure. There was a door-to-door research and participants wanted to know about the study aim. Also, the selected villages are isolated and the citizens may be poorly informed about dementia, depression, and its prevention. Besides, an important limitation was the sample size, which was small because of participants’ refusal or suspiciousness to answer. Furthermore, this sample compounds a small proportion of a specific region of Greece and may not be representative of the Greek population. The methodology for the clinical diagnosis may have resulted in differential outcomes. Methods 1 and 2 for MCI diagnosis were based on the MMSE and a depressive scale, whereas methods 3 and 4 were based on Petersen criteria. Although we compared our results according to method 4 in discussion, we must take into account the different methodology used in other researches.

The response rate in this survey is 25.6%. However, it is very common in Greece that a person is registered in a village but they actually leave in urban areas. Considering this fact and deducting the 546 individuals who could not be found, the response rate increases to 37.5%. Moreover, there are studies that show that surveys with a low response rate are not necessarily low in validity. A study from Visser et al showed that a response rate of as low as 20% can give more accurate results than a survey with a response rate of 60% or more. ⁹⁰