Egyptian Journal of Psychiatry

ORIGINAL ARTICLE
Year
: 2018  |  Volume : 39  |  Issue : 2  |  Page : 57--65

Cognitive impairment in elderly depressed and dementia patients in relation to plasma lipids


Ahmed A Abdel Hamid1, Hani H Dessoki2, Maged A Gomaa1, Mohamed R Soltan3, Ahmed A Abdel Hakim2, Marwa S Ahmed3,  
1 Department of Psychiatry, Faculty of Medicine, Cairo University, Cairo, Egypt
2 Department of Psychiatry, Faculty of Medicine, Beni Suef University, Beni Suef, Egypt
3 Department of Psychiatry, Faculty of Medicine, Fayoum University, Fayoum, Egypt

Correspondence Address:
Maged A Gomaa
Department of Psychiatry, Kasr Al-Ainy Faculty of Medicine, Cairo University, El-Manial, Cairo, 11562
Egypt

Abstract

Objective The aim was to study the relation between plasma lipid severity of cognitive impairment in elderly patients with depression and dementia. Background Cognitive functions are related to changes in lipid profile. Materials and methods Two groups of participants were studied: group A (patient group) included 60 patients subdivided into two subgroups: 30 patients who currently have dementia as a whole without taking into consideration the different kinds of dementia, but after exclusion of vascular dementia, and 30 patients with depressive disorders. Group B (control group) included 30 normal participants selected from among volunteers matched to the patient group for age, sex, education, sociodemographic, and economic status. They were subjected to the following: a psychological assessment that included the geriatric depression scale, the Wechsler memory scale − revised short form, and plasma lipid concentration assessment (overnight fasting blood was collected from each participant by standard venipuncture). Results The results of the study clarified that dementia patients showed more statistically significant impairment in cognitive functions than depressed patients in terms of the Wechsler memory scale − revised. The mean values of the blood cholesterol level, low-density lipoprotein, and high-density lipoprotein in the depressed group were significantly higher than those of the dementia and control groups. Conclusion There is a relation between cognitive impairment in depressed and dementia patients and plasma lipid concentration.



How to cite this article:
Abdel Hamid AA, Dessoki HH, Gomaa MA, Soltan MR, Abdel Hakim AA, Ahmed MS. Cognitive impairment in elderly depressed and dementia patients in relation to plasma lipids.Egypt J Psychiatr 2018;39:57-65


How to cite this URL:
Abdel Hamid AA, Dessoki HH, Gomaa MA, Soltan MR, Abdel Hakim AA, Ahmed MS. Cognitive impairment in elderly depressed and dementia patients in relation to plasma lipids. Egypt J Psychiatr [serial online] 2018 [cited 2018 Jul 22 ];39:57-65
Available from: http://new.ejpsy.eg.net/text.asp?2018/39/2/57/231697


Full Text



 Introduction



Late-onset depressive disorders are common and disabling (Naismith et al., 2007). Hence, these conditions are now the focus of considerable public health and clinical attention (Kessler et al., 2010). Depressed elderly patients often have cognitive impairments that are substantial, prevailing, and disabling (Butters et al., 2004). Even after effective treatment of depression, cognitive response is variable, and impairments often persist (Nebes and Pollock, 2003).

Dementia is not a single disease, but rather a nonspecific illness syndrome (i.e. a set of signs and symptoms) in which affected areas of cognition may be memory, attention, language, and problem solving (Caplan and Rabinowitz, 2010).

Cross-sectional studies have described an association between atherosclerosis, for which hypercholesterolemia is an important risk factor, and Alzheimer’s disease (AD), whereas longitudinal studies suggest a relationship between elevated midlife cholesterol levels and late life cognitive impairment or AD (Kivipelto et al., 2001). Also, there is a link between increased cholesterol and depression as suggested by Marie et al. (2010).

 Aim



The aim was to study the relation between plasma lipid concentrations with dementia and depression in the elderly and to assess in detail the relation between plasma lipid concentrations and the severity of cognitive impairment in elderly patients with depression and dementia.

 Participants and methods



This is a hospital based, cross-sectional comparative study with consecutive referral. The sample of this study was recruited from the psychiatric outpatient clinic of Beni-Suef University Hospital. The sample consisted of three groups: group A included 30 elderly patients with depressive disorder and included individuals diagnosed with major depression, dysthymia, or depression not otherwise specified as diagnosed according to diagnostic and statistical manual, fourth edition, text-revised (DSM-IV-TR), group B included 30 patients with current nonvascular dementia (patients with vascular dementia were excluded from the sample through assessment of history and neurological examination); and group C (control group), which included 30 normal participants selected from among volunteers matched to the patient group by age, sex, education, and sociodemographic and economic status.

All participants were subjected to the following:The Wechsler memory scale − revised (WMS-R) (Wechsler, 1987). The WMS-R comprises a series of brief subtests, each measuring a different facet of memory. The eight subtests measure short-term learning and recall of both verbal and figural material; verbal stimuli are read to the examinee and figural stimuli are presented visually. The verbal and figural subtests are alternated to provide variety and to help maintain the examinee’s attention. The eight tests contribute toward the assessment of the General Memory (five subtests) and Attention/Concentration/Psychomotor speed (three subtests). The General Memory group is further subdivided into two subgroups measuring Verbal Memory (two subtests) and Visual Memory (three subtests). The test takes around 35 min. The subtests that are presented to the participants as verbal stimuli are available in an Arabic version.The geriatric depression scale was used, which includes a 30-item self-report assessment designed specifically to identify depression in the elderly. Scores from 0 to 9 indicate no depression, scores from 10 to 19 indicate mild depression, and scores from 20 to 30 indicate severe depression.Plasma lipid concentration assessment was performed by collecting overnight fasting blood samples from each participant by standard venipuncture.

The results were determined according to the Adult treatment panel III (ATP III) Classification of LDL, Total, HDL Cholesterol and Triglycerides (mg/dL) as shown:LDL Cholesterol<100 Optimal100–129 Near optimal -above optimal130–159 Borderline high160–189 High≥190 Very highTotal Cholesterol<200 Desirable200–239 Borderline high≥240 HighHDL Cholesterol<40 Low≥60 HighTriglycerides<150 Optimal150–199 Borderline high200–499 High>500 Very high.

Statistical design and analysis

The results from the questionnaires were collected, revised, coded, tabulated, and statistically analyzed using Microsoft Excel (Microsoft, USA) and SPSS programs (SPSS Inc., Chicago, Illinois, USA). There were descriptive and comparative types, where quantitative data were summarized as mean and SD, whereas qualitative data were summarized as numbers and percentages. A comparison was made using paired Student’s test (t-test) for quantitative data of two groups and one-way analysis of variance (F-test), followed by Benferroni post-hoc test for multiple comparisons. The χ2-test was used for qualitative data. Variables that significantly affected the prevalence of a dual diagnosis in substance abuse in this initial analysis using the χ2-test were introduced into the regression analysis model. Different sets of regression analysis were created for each group of variables, and then all the significant variables were grouped into two final regression analyses to evaluate the effects of the different independent variables on the dependent variable. Differences were considered significant if the P value was less than or equal to 0.05.

 Results



The sample in this study included three groups depressed group (N=30), Demented group (N=30) and control group (N=30). The mean age in each is 66.3 years, 66.6 years and 64.7 years respectively. Male patients constituted 46.7% of the depressed group, 40% of demented group and 56.7% of the control group while female patients constituted 53.3% of the depressed group, 60% of the demented group and 43.3% of the control group. There were no statistically significant differences between the three groups regarding age, gender, educational level and occupational status as shown in [Table 1].{Table 1}

Mean scores of the control group were significantly higher regarding Figural memory, Logical memory I, Visual paired associates I, Verbal paired associates I (hard), Verbal paired associates I(easy), Visual reproduction I, Digit span ,and Visual memory span than mean scores of the depressed group ,while there were no significant difference between the two groups as regarding both Information and orientation and Mental control, in addition. On the other hand, the mean scores of the dementia group showed more statistically significant impairment in cognitive functions than both control and depressed groups ([Table 2] and [Table 3]).{Table 2}{Table 3}

Depression was assessed by using Geriatric Depression Scale (GDS). rersults showed that the mean score of depressed patient is significantly higher than that of both dementia and control groups. On the other side there was no significant difference between dementia and control group ([Figure 1],[Figure 2],[Figure 3],[Figure 4]).{Figure 1}{Figure 2}{Figure 3}{Figure 4}

Plasma lipids assessment showed that there were no significant differences between the two groups regarding Cholesterol blood level, LDL and TGs on the other hand, depressed patients have significantly higher HDL blood levels than control group ([Figure 5]).{Figure 5}

Besides, there were no significant differences between dementia group and control group groups regarding both Cholesterol blood level and TGs while, dementia patients have significantly higher HDL blood levels than control group ([Figure 6]). On the other hand, depressed patients have significantly higher cholesterol and LDL blood levels than demented group, while there were no significant differences between the two groups regarding both HDL and TGs ([Figure 7]).{Figure 6}{Figure 7}

The differences between the three groups regarding chemical tests, this study showed that the mean of the Blood cholesterol level, LDL and HDL were significantly higher in the depressed group are than both dementia and control groups ([Figure 8]).{Figure 8}

 Discussion



The main results of this study were as follows: there were no significant differences between the three groups in age, sex, level of education, and occupational status ([Table 1]). The control group had significantly higher figural memory, logical memory I, visual paired associates I, verbal paired associates I (hard), verbal paired associates I (easy), visual reproduction I, digit span, and visual memory span scores than the depressed group, whereas there were no significant differences between the two groups in both information and orientation and mental control. In addition, the dementia group had significantly more impairment in cognitive functions than the control group; furthermore, dementia patients showed more significant impairment in cognitive functions than depressed patients ([Table 2] and [Table 3]).

In terms of the differences between three groups in the geriatric depression scale. [Figure 1] shows that the mean score of depressed patients was significantly higher than that of both the dementia and the control group. However, there was no significant difference between the dementia and the control group ([Figure 2] and [Figure 3]).

In terms of the differences between the depressed group and the control group in chemical tests. [Figure 4] and [Figure 5] showed that there were no significant differences between the two groups in cholesterol blood level, LDL, and TGs; in contrast, depressed patients had significantly higher HDL blood levels than the control group.

In addition, there were no significant differences between the dementia group and the control group in both cholesterol blood level and TGs, whereas dementia patients had significantly higher HDL blood levels than the control group ([Figure 6]). However, depressed patients had significantly higher cholesterol and LDL blood levels than the dementia group, whereas there were no significant differences between the two groups in both HDL and TGs ([Figure 7]).

The differences between the three groups in chemical tests in this study showed that the mean blood cholesterol level, LDL, and HDL were significantly higher in the depressed group than both the dementia and the control group ([Figure 8]).

In the depressed group, on using the WMS-R subtests for assessing attention, concentration, and psychomotor speed using the (mental control, digit span and visual memory span) WMS-R subtests, on assessment of verbal short-term memory (logical memory and verbal paired associates), and on assessment of visual short-term memory (figural memory, visual paired associates, and visual reproduction), there was a highly statistically significant impairment in the depressed group than the control group. These results are in agreement with those obtained by Hammar and Ardal (2009), who found that there are impairments in different cognitive domains, such as executive functions, attention, memory, and psychomotor speed.

Despite numerous studies on cognitive functioning in major depressive disorder, there is no agreement on a conclusive neuropsychological profile characterizing depression. However, three hypotheses have been postulated to explain the cognitive impairment in this disorder: (a) a global-diffuse hypothesis, which states that MDD patients show a generally lowered cognitive profile, suggesting a global-diffuse impairment on a range of cognitive domains. (b) A hypothesis of specific cognitive impairment, suggesting that MDD is associated with pronounced impairment in specific cognitive domains, mainly in executive functioning and memory. (c) Irrespective of the domain, the cognitive effort hypothesis claims that MDD patients show impairment in effortful tasks, whereas they show normal functioning on automatic tasks. Automatic processing is stimulus driven, whereas effortful processing requires attention and cognitive capacity, and is also defined as an instruction-driven process (Hammar and Ardal, 2009).

In addition, in a cross-sectional study evaluating 100 patients, 60 years of age and older, who fulfilled the DSM-IV criteria for current episode of unipolar, nonpsychotic, major depression by a comprehensive neuropsychological battery, relative to the control participants, depressed patients performed poorer in all cognitive domains (more than half had significant cognitive impairment). Information processing speed and visuospatial and executive abilities were most broadly and frequently impaired. The neuropsychological impairments were mediated almost entirely by slowed information processing. The study concluded that depressed patients are characterized by slowed information processing, which affects all realms of cognition (Butters et al., 2004).

In this study, on assessing attention, concentration, and psychomotor speed in the dementia group by the WMS-R subtests (mental control, digit span, and visual memory span), there was a highly statistically significant impairment in the dementia group than the control group.

These results are in agreement with those obtained by (Melissa et al., 2002), who studied 49 patients diagnosed with probable AD; standard WMS subtests were used. Impairment demonstrated by patients with dementia in establishing and maintaining mental set errors of omission and commission were tallied for all dementia participants. Authors speculated that errors of omission may reflect a degraded, yet still functional, ability to maintain mental set, while errors of commission may reflect a greater degree of impairment in establishing and maintaining mental set and executive control i.e. the ability of patients to appreciate and understand the nature of a task, and to respond within the context of that task until the task is completed (Libon et al., 2004).

On assessing logical memory recall in the dementia group, there was a highly statistically significant impairment in the dementia group than the control group. This was consistent with data from a study of three groups of older adults identified and retrieved from the archival records of a longitudinal study of healthy aging and dementia of Alzheimer’s type (DAT). The effect of dementia was primarily one of decrease in immediate recall, with little additional effect after the delay interval (David and Martha, 2003).

In addition, on assessing logical memory and visual reproduction (WMS-R subtests) in the dementia group, there was a highly statistically significant impairment in the dementia group than the control group. This was consistent with a study of 73 patients, aged 50–84 years, tested by visual and verbal memory tests (visual reproduction subtest of the WMS-R, logical memory subtest (WMS-R). Marked impairment in visual reproduction and immediate recall of information from the story was found in AD patients. This deficit can be attributed to problems in attention, coordination, and integration processes stemming from impaired executive control processes (Claudia et al., 2008).

In terms of the relation between depression and total cholesterol, the data in this study showed that total cholesterol has a positive correlation with depression. Similar results were obtained by Tanskanen et al. (2000), who found a positive relationship between high serum total cholesterol levels and depression.

Also, this was confirmed through another study that hypothesized that depression is a kind of chronic stress; this stress response system is indirectly linked to proinflammatory signaling. The stress response involves the release of tumor necrosis factor-α and interleukin-6, which increase the release of corticotropin releasing hormone, adrenocorticotropic hormone, and cortisol by acting directly on hypothalamic and pituitary cells. Dysregulation of the hypothalamic–pituitary–adrenal axis is an important finding associated with depressive behavior (Yekta et al., 2010).

In addition, several reports in the literature have suggested that vascular risk factors such as smoking, hypertension, and increased serum cholesterol play a putative role in the etiology of depression. There is also neuropathological evidence for an excess of atheromatous disease in the aortic and cerebral vessels in late life depression (Thomas et al., 2001). On the basis of these findings, several researchers have postulated a ‘vascular depression’ hypothesis (Alexopoulos et al., 1997); this hypothesis argues that for a subset of patients, depression may be caused by cerebrovascular disease manifesting as small lacunae in the subcortical gray and the white matter. These lesions would then disrupt the prefrontal systems related to mood regulation or the white matter pathways connecting these areas with other parts of the brain (George et al., 2004).

Moreover, antidepressant medications are often associated with weight gain and metabolic abnormalities in vulnerable patients (Pratap et al., 2006).

However, there are a number of studies on an association between low cholesterol levels and major depression, including a large Finnish study involving over 29 000 men that assessed cholesterol levels in patients with various mood disorders including bipolar disorder, MDD, and schizoaffective disorder, and found significantly lower cholesterol levels in patients experiencing manic or depressive episodes compared with patients experiencing mixed episodes (Rafter, 2001). Low cholesterol levels have also been found to lead to an increased risk of MDD (Horsten et al., 1997).

These inconsistencies among the various reports appear to suggest that the link between plasma total cholesterol and the occurrence of depression is less straightforward than it might seem, probably because of factors such as age, other clinical conditions, nutritional factors, or other life style factors that modulate plasma lipids (Onuegbu et al., 2007).

In terms of the relation between depression and TGs, in this study, no significant relation was found between depression and TGs. This was consistent with a study carried out by David et al. (2005), who found that triglyceride levels were not significantly associated with major depression.

In contrast, depression has been linked to metabolic abnormalities, such as abdominal obesity, high blood pressure, high triglycerides, and insulin resistance (Vitaliano et al., 2002).

In terms of the relation between dementia and total cholesterol, in this study, there was a significant relation between dementia and low blood levels of total cholesterol. These results were in agreement with a study carried out by Max (1957), who found that low cholesterol resulted in increase in Alzheimer’s disease. It was found that as we get older, the level of cholesterol in our brains declines. Later studies suggested that this decline may be the cause of cognitive impairment and Alzheimer’s disease. In 1991, a paper discussing the relief of Alzh­eimer’s disease, asked that ‘strategies for increasing the delivery of cholesterol to the brain should be identified’ and recommended increasing fat intake (28). Another recent study found that there are conflicting evidences regarding the role of cholesterol and dyslipidemia in the evolution of AD, alteration in levels of cholesterol and HDL was related to AD (Reitz, 2013).

Several Research work enriched the beneficial role of HDL in preserving cognitive functions under normal and pathological conditions, whereas alterations in HDL levels is associated with cognitive decline in neurodegenerative disorders (Hottman et al., 2014).

In addition, AD can be explained by multiple theories rather than cholesterol blood levels as in a study carried out by Farrer et al. (1997), who found that the ϵ4 allele of the apolipoprotein E gene (APOE-ϵ4) has been confirmed to be a genetic risk factor for late-onset AD in multiple genetic backgrounds.

Besides, Tau hyper phosphorylation and neurofibrillary tangle formation within cortical glutamatergic neurons have long been associated with cognitive decline and more recently with the development of behavioral symptoms in patients with AD. In particular, a greater burden of neurofibrillary tangles, determined histopathologically, in anterior cortical areas has been correlated with higher agitation scores and aberrant motor behavior (Senanarong et al., 2004).

In terms of the relation between dementia and TGs, in this study, no significant relations were found. This was consistent with a study carried out on a population of older Greek community-dwelling adults. The participants were classified into three groups: the dementia group included 37 patients and the depression group included 33 patients. In parallel, a group of 33 controls was selected randomly from the same population. No significant difference was found between the dementia and the control group (Nikolaos et al., 2007).

Moreover, Henderson et al. (2003) reported that there are insufficient data for TG alone, although some studies have shown no relationship between memory and TG levels. Importance of this study is that it emphasizes the role of plasma lipids in the development of depression and its relationship with cognitive impairment in the elderly. Some studies considered low levels of HDL and high levels of LDL as a biomarker of Major depressive disorder (Parekh et al., 2017) as a part of atherosclerotic changes in the brain, supporting the concept of vascular depression (Ong et al., 2016).

 Limitations



A small sample size and use of different antidepressant and dementia drugs are the most important limitations of this study. The study was designed to assess the cognitive performance of elderly patients with MDD and dementia without further investigation of the possible etiological factors that may be implicated in the pathogenesis of late life depression and comorbid cognitive impairment. The study did not categorize the patients who fulfilled the criteria of mild cognitive impairment (MCI). The influence of the educational level on the results of this study cannot be ruled out as a confounding factor.

Acknowledgements

All authors contributed to every activity of it; idea of paper, study design, collection of materials, methodology, writing the paper, and revising it.[38]

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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