Genetic factors.

Genetic variations of serotonin-transporter-linked polymorphic region (5-HTTLPR) were analyzed in a study of Austrian older people and yielded no significant results for occurrence of 5-HTTLPR short allele [31]. A study of 415 older French women assessed GPR50 polymorphisms (melatonin-related receptor) located on the X-chromosome and found that homozygotes for the minor allele of rs561077 were a risk factor for incident depression in women, but the polymorphisms rs13440581 and rs2072621 were not found to increase risk for depression [14]. A German study looked at Apolipoprotein E and compared having at least one 4-allele with having no 4-allele with insignificant results [2].

Developmental factors.

Lower childhood socioeconomic status was identified as a positive risk factor in one study of medium quality [22].

Sociodemographic and relationship characteristics.

Older age was identified as a risk factor in five studies [2,38,41–43] but was not significant in eleven studies [18,24,26,27,29,30,35–37,40,44]. Additionally, older age was insignificant in both men and women analyzed separately in one study [18] and increased risk for depression in women, but not in men in another [20]. Female gender was associated with more cases of incident depression in seven studies [18,26,37,41–44] but insignificant in ten studies [2,24,27,29,30,31,36,38–40]. Marital status was also assessed in ten studies [2,18,20,26,29,36,37,41–43], but did not reach significance. “Never being married” was also investigated by two studies [40,43] and found to be insignificant. In both high and medium quality studies significance and non-significance for the factor were results of the analyses. Also, living alone versus living with others did not reach significance in any of the studies investigating that factor [2,24,25,29,37]. Similarly, significant results were not found for living in an institution/nursing home [37], living in a rented home [22] or changing a living situation [31]. However, in Nigeria rural residence is a risk factor for depression in women, but not in men. These results were consistent in two studies of the same cohort [18,19]. Furthermore, rural residence was insignificant in a Japanese study. One Swedish study of 894 older people found use of care (home care), as well as use of institutionalized care to be insignificant [40]. Lower education was identified as a risk factor in four studies [30,41–43] but was insignificant in 12 others [19,20,22,24–26,29,31,36–38,40,44] and also in men and women individually. Noteworthy, only one study of high quality found education to be significant, whereas in five studies “lower education” was insignificant. One study found “middle level” of education, but not “high level” to be a protective factor against incident depression [2]. A Japanese study [22] reported “lower income” as a risk factor for incident depression, although and English study found that it was not significant [41]. Similarly, “lower income” was not a risk factor for both in men and women in another Japanese population [20]. Furthermore, economic status yielded no significant results for men and women in Nigeria [18,19]. Similarly, a number of factors asssociated with economic status, such as source of water supply and source of energy for cooking, did not reach significance in the same Nigerian cohort [19]. In terms of “longest held occupation”, there were no significant results when comparing manual, non-manual and no occupation [22]. A study of European older people found financial stress to be a significant risk factor [43] and a Taiwanese survey identified worsened financial stress as a significant risk factor [26]. Immigrant status was analyzed by one study, but did not increase the risk for depression [40]. Additionally, an American study found that having been raised in the USA was a protective factor for white people, [30] while a lower quality US-study reported contrary results [29].

Lifestyle factors.

Participating in a physical activity was identified as a protective factor by one study of medium quality [30] However, a Finish sample of non-institutionalized seniors did not find a significant difference between the onset of depression in the subgroups disabled-sedentary, disabled-active, and mobile-sedentary as compared to a mobile-active subgroup in multivariate analysis [38]. In another study, some specific forms of physical activity, such as walking habits and moderate physical exercise, yielded insignificant results, however light physical exercise was found to be a protective factor [23]. Furthermore, household and locomotive activities time per day and habits of going out were not significant, although it was found that more than 240 minutes of sedentary time per day increased risk for incident depression in a study of 3066 Japanese older people [25]. The analysis of “current smoking” yielded varying results in studies of high- and medium quality: three surveys stated it to be a risk factor [2,41,42], whereas three studies found no significant association [24,25,30]. Additionally, being ex-smoker was insignificant in a study of older people in the U.K. [41]. Alcohol consumption was insignificant in all five studies analyzing the diversely defined factor [2,24,25,30,41]. However, a German study found at-risk drinking to be a risk factor [37]. A face-to-face interview study of Japanese older people identified taking enrichment lessons and using a personal computer as protective factor against incident depression, and yielded insignificant results for operating video or DVD-player [23].

Mental health status/history.

Analysis of the history of mental health disorders revealed varying results. “History of mental disorder” as such was identified as a risk factor in one study [35]. A history of depression resulted as a risk factor in the only study rated “low quality” [29], but was not significant in an Austrian study of medium quality [31]. Analysis of “history of depression or anxiety” as a risk factor also yielded a significant association to more incident cases of depression in one survey [40], but was not significant in another [36]. A history of psychosis was not significant in one of these studies [40]. The study of low quality also yielded no significant results for “current alcohol related or anxiety disorder” at baseline as a risk factor [29]. Subsyndromal depression at baseline [18] and delirium in preceding month [39] also did not result in significant findings. Depression-score at baseline was identified as a risk factor in one study [39], although it was insignificant in another study of lower quality [29]. Family history of mental illness was not significant in all surveys that analyzed the factor [36,37]. In addition, despite frontal executive function tested with Trail Making Test Part B not being significant [31], poor cognitive function increased the risk of incident depression according to three studies [2,31,43], although four studies found no significant association [24,29,36,37]. Furthermore dementia at baseline did not increase risk for depression in two studies of medium and lower quality [29,40].

Physical health status.

Various factors related to the presence of physical illnesses were analyzed with mostly insignificant results. Multivariate analysis of a cumulative illness score [29], having somatic illness [2,20,40], and having severe illness [31] all produced insignificant results. However, one survey identified “number of illnesses” as a risk factor [41], although the factor resulted insignificant in two other studies [2,38]. Equally, occurrence of new disease/new medical illness was not significant [26,36]. In contrast, poorer self-rated health was identified as a risk factor in four high-quality and medium-quality surveys [24,37,43,44] and only for men in another study [20]. Notwithstanding that in a study of medium quality [39] and lower quality [20,29], as well as separately for women [20] no significant results were found for this factor. Moreover, worsened self-rated health in a Taiwanese sample [27] was insignificant. Interestingly, “chronic disease” increased risk for depression significantly in all studies testing this factor for the whole sample [18,35,36,43], although no significant results were found in men and women separately. Likewise, new chronic disease [35] and the worsening of perceived health stress [26] were significant risk factors.

History of stroke/stroke in the past was a significant risk factor according to two studies [37,39], but “ongoing medical condition: stroke” was insignificant in another study [27]. Similarly, a new stroke in last 30 months was not a risk factor [31]. History of other specific somatic diseases was mostly insignificant. Likewise, history of myocardial infarction [37,39], history of lung disease, history of bone disease and history of cancer [42] did not reach significance. Other factors related to cardiac health such as myocardial infarction within last 30 months and coronary heart disease [31] remained insignificant. However, pre-existing heart disease was identified as a risk factor in a study [27,28], as was ongoing heart disease [27], but heart disease, defined as positively endorsing the question: “has your doctor ever told you, that you have (or had) any of the conditions on this card”, was insignificant in one study [42]. Furthermore, newly diagnosed cancer [31] and ongoing cancer [27] were not significant risk factors. In contrast, ongoing arthritis or rheumatism [27] increased risk of incident depression. More severe pain [42] and emergent pain [31] were identified as risk factors, although chronic pain yielded insignificant results for Nigerian men and women separately [18]. Illness of relatives was not a risk factor of incident depression [31]. With regard to vascular risk and depression, lower HDL cholesterol levels [28] and hypertension [39] were identified as a risk factors, although hypertension was not significant in another analysis [27] and low HDL-cholesterol was insignificant in older French women [32]. Surprisingly, low LDL-cholesterol increased risk of incident depression in French men [32]. Other factors related to vascular risk, such as another vascular risk factors not specified [31], diabetes [27,42], systolic blood pressure, diastolic blood pressure and higher BMI [30], were not significantly associated with incident depression.

Concerning medication, mean number of medications [39], taking anxiolytic medication [39], as well as taking antihypertensive medication [30] were all insignificant, whereas “using sleep medication” was a significant risk factor according to a high-quality survey [25]. Four studies analyzed the influence of sleep disturbances on depression. In a study of elders in the USA, analysis of a subsample of participants 75 years and older found two or more insomnia symptoms to be a risk factor of incident depression [30,44], as well as a Japanese study defining insomnia as difficulty in initiation or maintainance of sleep with a frequency of 3 night per week in the past month. Furthermore, difficulty initiating sleep and difficulty of maintaining sleep, but not poor sleep quality and early morning awakening, where significantly associated with depression onset [34]. A Japanese study found difficulty initiating sleep, but not difficulty maintaining sleep, early morning awakening, or excessive daytime sleepiness to be associated with depression onset [44].

A German study yielded no significant results for hospitalization during the last year [37], but found that two or more specialists visits in the last 12 months increased risk for depression [37].

Impairment.

Measures of impairment where significantly associated with incident depression in several included longitudinal studies. Mobility impairment increased risk for incident depression significantly according to three studies [2,41,42]. Four studies found IADL impairment to increase risk for incident depression [35,36,41,42], although the factor did not reach significance in two other studies [2,29], nor in two further studies analyzing men and women separately [18,20]. Furthermore, ADL impairment was identified as a risk factor in one [43], but was insignificant in six studies [36,37,40–42,44]. Change of impairment was analyzed separately in some studies: worsened IADL impairment was identified as a risk factor in three studies [26,27,35,36], worsened mobility impairment was insignificant in one study [27], whereas worsened ADL- impairment was only significant in one [27] but not another study [36]. Visual impairment increased risk for depression as stated by three included publications [2,41,42], while results were insignificant in another survey [40]. In addition, a study of French older people found distance visual function loss and near visual impairment at baseline to be insignificant, but a 2-year decrease in distance visual function to be a risk factor [37]. Hearing impairment [2,39,41,40] and visual and hearing impairment analyzed together did not reach significance [41]. Physical frailty [24] and gait speed slower than one meter per second [25], but not fear of falling [25], increased risk for depression in two studies. From one study of Austrian older people, having a “handicap” was reported to be insignificant, without specifying the assessment method [31]. A study of 384 Finnish older people yielded no significant results for disabled sedentary vs. mobile active and disabled active vs. mobile-active groups [38] with mobility being assessed of self-reported ability to walk two kilometers and to be able to climb one flight of stairs without difficulty. One study included Instrumental Activities of Daily living score, Global Assessment of Functioning score and Karnofsky Performance Status scale into the analysis, all of which remained insignificant [29], although Physical self-maintenance score >0, indicating poorer functioning, was significant.

Psychosocial factors.

The protective attribute of family support against depression onset was found to be significant in one study [41]. Furthermore family negative interaction was identified as a risk factor in two studies [41,42], although insignificant in another study of lower quality [29]. Per contra, frequency of contact by family and emotional support by family [42] yielded insignificant results. In addition, “no regular contact with family” was insignificant in Nigerian men and women individually in one study [18], but was a risk factor in women in another study analyzing the sample [19]. Receiving lower instrumental social support as assessed by the Duke Social Support Index [29] and worsened instrumental social support and worsening of received emotional social support as assessed by self-report using a five-point Likert-scale [26] revealed no significant results. A study analyzing older Japanese women and men separately, found receiving and providing emotional social support, as well as receiving and providing instrumental social support to be insignificant [20]. A higher sense of coherence was identified as a protective factor for both women and men, although a higher frequency of meeting with friends and having hobbies was protective for men, but not for women [20]. Furthermore, participation in organizations yielded no significant results in the same study [20]. Loneliness resulted as significantly increasing the risk of depression in one [43], but was not-significant in another survey [39]. In a study from northern Japan, negative answers to the questions: “Do you have someone with whom you can consult when in trouble?”, as well as “Do you have someone who can to take care of you when you are ill in bed” increased risk of depression significantly, although negative answers to the questions: “Do you have someone to take you to the hospital when you do not feel well?” and “Do you have someone with whom you can consult when in your physical condition is not good?” did not [21]. Higher social network score, indicating a more complex social network, assessed with a social network index in a German study [37], as well as participating in events in community center and attending a community meeting in Japanese older [23] were identified as protective factors against incident depression. In contrast, being called on for advice, having no regular visitors, having no friends and being unsatisfied with the social network did not significantly increased risk for depression in a Swedish sample [40]. Still, decreased life satisfaction was identified as a risk factor for depression [26]. Two studies analyzed social factors for incident depression separately for men and women. In a Japanese study, receiving and providing emotional and instrumental social support were not significant for both men and women; participation in organizations was also not significant [20]. In a Nigerian study, lack of regular contact with family was not found to be significant [18]. However, higher sense of coherence, as assessed by a 13-Item Sense of Coherence scale (SOC-13) was a protective factor for both men and women in Japan, while frequency of meeting with friends 1–2 times per week or more was identified as a protective factor for men, but not for women [20]. In contrast, the Nigerian survey found that having no regular contact with friends increased risk for depression in women, but not in men [18]. However, a later study of the same sample found significance in neither men nor women and additionally found no significant results for participation in family activities or participation in community activities [19]. Having hobbies yielded protective in men, but not in women in the Japanese study [20].

Life stressors.

Stressful life events were analyzed as potential risk factors in four studies but did not yield significant results. However, having experienced stressful life events was defined differently in each study: [37] defined positive outcome as at least one event in last 6 months, [29] used a modified version of Louisville Older Persons Event Scale, [31] used a modified version of the Life Event and Difficulties Schedule by Brown and Harris, and [18] employed the List of Life Threatening Events 12 months prior to baseline for both men and women. A Japanese study analyzed factors separately for men and women and found a significant positive association of one or more stressful life events in the 12-months prior to the follow up for both men and women [20]. However, as life events were not assessed prior to baseline, this association cannot be interpreted as a risk factor. Two papers analyzing a sample in the Netherlands identified loss of spouse as a significant risk factor [35,36]. Furthermore the Austrian study found “bereavement” to be insignificant, but “troubles with relatives” to be protective against depression [31]. Participants affirming presence of psychological stress in their daily lifes also had a significantly higher incidence of depression in one study [44].

MRI alterations.

One study examined MRI changes as potential risk factors, but yielded insignificant results for progression of white matter or periventricular hyperintensities in MRI, cella media index in MRI, and atrophy of medial temporal lobe in MRI [31].

Genetic factors.

The insignificant result of 5-HTTPLR serotonin transporter promoter region short allele matches with results of a recent large meta-analysis focusing on a gene-environment interaction with 5-HTTPLR polymorphisms, stress and depression that found no significant interaction [51]. Research on GRP50 polymorphisms is scarce yielding mixed findings for connection between polymorphisms and mood disorder [52,53], although one included study in this review found a increase of risk by GPR50 polymorphism rs561077 for incident depression which makes further research necessary. The APOE allele being insignificant in our findings supports the assumption of a previous study that found associations between ApOE4 alleles and depression might be due to confounding through individuals with Alzheimer’s disease [53], as demented patients were excluded and mild cognitive impairment was controlled for in the included study [2,11]. In addition, this result is consistent with previous longitudinal findings [11].

Developmental factors.

Only one study analyzed self-rated childhood socioeconomic status finding it to increase risk for depression. Still, this result must be interpreted with precaution as recall bias might be high in this type of self-rated question concerning long past circumstances. Longer longitudinal studies assessing socioeconomic status objectively in childhood and adolescence are needed to produce more robust results for the relation to depression in late life.

Sociodemographic and relationship characteristics.

Frequently analyzed factors rarely delivered homogenous results regardless of the quality of the involved studies. Findings on older age do not paint a clear picture, as twice the number of studies that identified older age as a risk factor, did not find a significant association. Gender also delivered heterogenous results, although male gender never increased risk for depression. In addition, lower education cannot be clearly stated as a risk factor, as it was more often insignificant than a risk factor, especially in high quality studies. In addition, a study of higher quality identifying middle-level, but not high-level education, as protective indicates that a simple dichotomous view on education might be oversimplified.

Financial factors were assessed in several studies. A study identifying the factor as risk factors used three subgroups according to income, with the lowest income group increasing risk for depression significantly [22] while a study analyzing total income in decile did not find a significant association [41]. Two other studies finding financial stress and worsened financial stress as risk factors might hint to lower income increasing risk for depression only when causing stress. Therefore, more research is needed for this set of factors. The identification of white ethnicity as a protective factor in one American study [30], but insignificant in study in New-York [29] might be due to the different methodological quality, or e.g. due to varying exposure to stressors in different communities. Marriage status seems to have no influence on depression onset, as it was frequently analyzed, but never significant.

Lifestyle factors.

Physical activity was assessed with varying self-reported questions. Reporting more physical activity in some specific areas was protective against depression. In one study “participating in physical activity”, defined as self-report of mild, moderate, or vigorous activity (vs. no physical activity), was identified as a protective factor [29]. However in a study adding different subgroups of mobility-and physical activity, “physical active” was defined as walking at least several times per week as reported by the participants [38] leading to insignificant results. Overall, the variety in very specific factors assessed by self-report, concerning physical activity might explain the finding of protective quality of some factors while others remained insignificant. Further research with more comparable instruments is needed.

Alcohol consumption was assessed diversely. In three studies frequency of alcohol consumption was self-reported and rated ordinally [24,25,41], whereas one study used a simple dichotomous yes/no format [30]. Only one study used a question quantifying the average daily level of consumption on an ordinal level [2]. All these studies yielded insignificant results. In contrast, a study assessing “alcohol at risk drinking” dichotomizing the variable according to consumption below or over the level determined by the British Medical Association and found it to be a risk factor. These findings suggest, that frequency of drinking does not increase risk for depression. However, quantity of alcohol consumption led to contradicting results using different cut-offs and needs to be analyzed further. Findings on smoking were also heterogenous. Therefore, we suggest assessing current and past smoking habits more specifically to obtain clearer results. A study measuring “cognitive activity” revealed inhomogeneous results, with self-reported “taking enrichment lessons” and “using a personal computer” as protective factors, but “operating video or DVD player” as insignificant. The short activity “operating a video or DVD player” would logically usually precede the less cognitively challenging activity “watching video”, which might explain the lack of protective quality of this factor.

Mental health status.

Whether a personal history of mental disorders increases risk of depression is difficult to interpret when the study [35] did not specify the definition of having a “history of mental disorders”. History of depression was only analyzed in two studies, leading to heterogenous results. Similarly, only half of the studies analyzing “history of depression” in a review of previous longitudinal studies could find a significant association [10]. Furthermore, depression score at baseline also led to heterogenous results. All other studied factors including subsyndromal depression at baseline, delirium in preceding month and history of psychosis did not increase risk of depression. Interestingly, our findings did not find a family history of mental illness to increase risk of depression and no previous survey has analyzed this factor longitudinally with multivariate analysis according to our knowledge [10,11]. Family history of mental illness was assessed by self-report and defined as inpatient treatment of mental disorders or suicide of a first-degree relative [37] or a question of family history of psychiatric illness [36]. The insignificant findings on family history of mental illness suits the findings of a previous cross-sectional twin study which provided hints that familiar history of depression might play a smaller role in depression onset in older rather than in younger subjects [54], although the sample of the study in question was much younger. Furthermore, these self-report questions might be vulnerable to information and recall bias. Cognitive function was frequently analyzed and found to be a significant risk factor, but results were heterogenous. This concurs with the results of five studies from a review of previous studies with participants 50+ or older [10] with similarly heterogenous results. The theory that realization of deteriorating cognitive function may lead to development of depressive symptoms secondary to cognitive decline was previously opposed [55]. However, it can nether be rejected nor supported due to de heterogenicity of our findings. Dementia did not increase risk of depression according to two of our included studies. Both studies use DSM-IV SCID to diagnose depression. However, the process of dementia might lead to symptoms that facilitate the diagnosis of depression such as hypersomnia, fatigue and weight loss. Therefore it is difficult to draw conclusions on the relationship between dementia and depression and the controversial topic is discussed for this reason inter alia [55].

Physical health status.

Factors depicting present physical health status at baseline more generally, such as cumulative illness score and “having somatic illness” and “having severe illness” were mostly insignificant in our findings, although frequently analyzed. Only “number of illnesses” delivered heterogenous results. These findings are consistent with a previous meta-analysis, which found “poor-health status” to be insignificant, although studies used for the meta-analysis found the factor to be a risk factor for depression. However, our findings suggest, that chronic disease, as well as new chronic disease increased risk for depression. Similarly, nearly all studies from earlier reviews found “number of chronic health conditions” to be a risk factor [11]. Additionally, poorer and worsening of self-rated health did not deliver homogenous results, although it was significant in three studies. Considered together with two older longitudinal studies of participants 65+, finding poorer self-rated health to be a risk factor [10], these findings make further research necessary. History of stroke, but not new stroke seems to increase risk for depression, although stroke more indistinctly defined as “ongoing medical condition” of stroke [24] did not increase risk for depression. Interestingly, all four studies assessing the factor suspended the influence of the potential confounders ADL and/or IADL impairment by adding them to multivariate analysis. Results for heart disease as a risk factors do not allow a clear conclusion to be drawn. History of myocardial infarction and myocardial infarction in last 30 months were insignificant, whereas pre-existing heart disease yielded heterogenous results. The definition of heart disease differed between these studies: [56] used previous diagnosis with clear time of onset, whereas heart disease was assessed as a “ongoing medical condition(..)”; [27] and [42] defined heart disease as positive answer to the question, “Has a doctor ever told you that you have any of the conditions on this card?”. Thus, heterogeneity of the results might be caused by recall-bias in some of the studies. Vascular risk factors require further research, as lower HDL cholesterol levels and hypertension increased risk for depression significantly in single studies, but several other single studies did not find significant results for factors such as hypertension, BMI and blood pressure. Furthermore, taking specific medications seems to have no influence on depression onset, except for sleep medication. This supports our findings on insomnia symptoms, especially difficulty initiating sleep being associated with depression. However, the two studies analyzing difficulty maintaining sleep had heterogenous results. In the previous literature, two of four longitudinal studies of older people assessing insomnia symptoms yielded similar findings [10,11]. Increased pain seems to lead to higher risk of depression, although chronic pain, as such, does not. However, due to the small number of studies analyzing the influence of pain, more research is needed. In addition, the increase in risk through hospitalization and two or more specialists visit in the last 12 months was identified in a German population. Since contact to health care professionals could be an opportunity for prevention, if their predictive value results to be high, these findings call for further analysis.

Impairment.

Impairment seems to increase the risk of incident depression, which is consistent with earlier reviews [10,11]. However, our findings make distinction between different measures of impairment necessary. Mobility impairment, IADL impairment, visual impairment, as well as worsening of IADL-impairment were frequently investigated and were found to be significant risk factors of depression in most studies. In contrast, less homogenous results for ADL impairment, or its worsening, hint to a lesser influence of this factor. In addition, our findings clearly suggest that hearing impairment does not increase the risk of depression.

Psychosocial factors.

The varying methods and specificity of psychosocial factors in included studies makes interpretation difficult. Nearly all factors were assessed by positive or negative self-reported answer to a specific statement and were highly specific. Only “loneliness” and “family negative interaction” were assessed in more than one study and yielded heterogenous results. In addition, the findings of two studies hint to modest differences in the influence of social behavior in men and women. However, higher scores in social network measurement scales, such as the Sense of Coherence Scale (SOC-13) [20] as well as the more complex instrument, the Social Network Index [37] hint to a protective quality of these factors. Overall, more research on the influence of social factors with instruments validly depicting these complex systems is needed.

Our findings suggest the conclusion, that stressful life events, in general, do not increase the risk of depression independently. However, “loss of spouse” was identified as a risk factor. The reason why “troubles with relatives” resulted to be protective in a study of medium quality is unclear.

Reevaluation of the conceptual framework.

Our findings allow a reevaluation of our conceptual framework. Genetic factors were only analyzed by single studies and therefore require further research. Furthermore, developmental factors such as childhood economic status require more research or might be available in longitudinal studies with younger age at baseline. Our findings could not unconditionally support commonly identified sociodemographic factors increasing risk of depression such as lower education, female gender and older age. In contrast, the frequently analyzed factor “marriage status” yielded homogeneously insignificant results. Concerning lifestyle factors, we found strong hints to a protective quality of some types of physical activity against incident depression, although further research with more comparable instruments is needed. Our heterogenous findings on drinking and smoking calls for assessment of frequency, quantity, and past consumption to obtain clearer results. Moreover, the protective effect of self-reported subtypes of cognitive activity only analyzed in one study calls for further investigation. Mental health status yielded heterogenous results on the influence of history of depression and cognitive function, whereas other factors, analyzed by single studies such as subsyndromal depression at baseline, delirium in preceding month and family history of depression remained insignificant. Apart from these factors, further research is needed for depression score at baseline, as previous diagnosis and depression questionnaires could potentially represent targets for screening. In factors related to physical health, chronic disease and insomnia symptoms had the clearest results to increase risk of depression with hints to a specific subset of insomnia symptoms having more influence. Factors related to stroke, heart disease, pain and vascular risk factors delivered heterogenous results and require further research. Our findings suggest a specification of the of impairment as a risk factor, as mobility, IADL- and visual impairment seem to increase the risk of depression, while we found less influence of ADL-impairment. Moreover, although frequently analyzed, hearing impairment apparently has no influence on incident of depression. Unfortunately, variety of methods for assessment of psychosocial factors does not allow a clear conclusion, although the results hint to a protective quality of a higher sense of coherence and a better social network. Studies analyzing factors concerning neurobiological and neuromorphological changes were scarce in this review, as only one study assessed MRI-alterations at baseline. These factors represent a wide and complicated field and are subjects of intensive research e.g. [15].