zalam's blog

The high androgen levels in women (mild to moderate AD) in low stress environments showed the altered metabolism of the androgens. The significant correlations between DHEA and cortisol, androstenedione and cortisol indicated that hormone production in the adrenal cortex of the kidneys were like that of younger people. In another study mentioned in this paper, associated high levels of cortisol and DHEA with cognitive dysfunction. There were higher chances of performing better with lower levels of DHEA. Later in the study, they had said that further investigation was required to assess the androgen and gonadal hormone metabolism as they had only reported increased basal androgen levels. In another study, they investigated the thyroid hormone levels in the cerebrospinal fluid (CSF – present to keep the brain afloat and washout any toxins) and found a correlation to the AD severity in patients with normally functioning thyroids. Thyroid hormone (TH) helps in metabolism in the brain and hence can be found in the CSF. There are several forms of TH – they are usually numbered as T_2, T₃, T₄etc. They used something called lumbar puncture to extract spinal fluid from people (sounds pretty painful!). They used highly specific techniques called mass spectrometry and high performance liquid chromatography to assess the CSF containing thyroid hormones. They had about 35 patients (9 males and 26 females, approximately 66 years). The CSF TH concentrations were representative of the blood TH concentration. The AD patients were diagnosed through CT scans, neuropsychological tests, MRI and Mini-Mental State Examination (MMSE). The control group had 10 subjects with normal cognitive abilities and normal MMSE. They had undergone lumbar puncture due complains of severe headaches. Exclusion criteria included thyroid problems, abnormalities of CSF routine analysis or any proof that the barrier between their blood vessels and brain was damaged by in depth analysis of the CSF. 

In a study, ghrellin was elevated in mice (either through caloric restriction or subcutaneous injections) showed less depressive like symptoms in forced swim test. On the chronic social defeat stress scale, ghr-KO mice showed more social avoidance than wild-type after periods of struggle with a dominant animal. Systemic treatment with a neuroprotective compount enhanced neurogenesis in the hippocampus leading to antidepressant effects - it was speculated that ghrelin’s antidepressant properties are mediated by neurogenic properties. The same effects were seen after administration in mice that had undergone olfactory bulbectomy, same with group with reduced AVP gene expression. Ghrelin also increases noradrenergic and serotonergic  transmission. Two studies suggested contrasting results - increased long term ghrelin caused depressogenic properties through decreased serotonergic transmission in the dorsal raphe nuclei and pro depression effects; and then injecting anti-sense strand into the lateral ventricle induced anti-depressant effects(but authors did not measure ghrelin level to give a clearer indication that the observed effects are related to ghrelin system).

The Perfect Paragraphs were easier to do since it was just improving a draft. However, the comments were slightly time consuming as sometimes people did not have improvements to make or sometimes the posts would have reached its limit for comments. The paragraphs helped me refine my writing further and realize that even though I am trying to proofread as I write, there are always corrections to be made if it is read once more at the end. The methods project was very different from all project reports I have written. I had never paid so much attention to detail as much as I had for this project. I personally had a great time doing a write up on it. It was a very unique way of understanding the whole idea of replication as well. I also found the approach for finding differences very interesting – making inferences for the differences rather than finding faults. 

Nevertheless, there is a growing body of research surfacing every now and then about potential biomarkers for diagnosing AD early and potential therapies. A study done in Umea University Hospital in Sweden looks at how hormones released by our adrenal glands (adrenocortical) and our reproductive organs (gonadal) can essentially help to detect AD in its early stages. Majority of the people diagnosed with this disease fall in the category of mid 60s and older. As our body ages, it is normal for our hormones to start depleting, especially reproductive ones (estrogen and testosterone). However, in this study, the findings were quite different. They were able to obtain 33 patients with mild to moderate AD (12 men and 21 women, aged approximately 76 years old). They were compared to 22 healthy patients who were already part of a Longitudinal study at the Umea Hospital. They were part of the control group that is usually present for comparison. They had exclusion factors that included medication use, acute medical illness, endocrine disorders, depression, infectious diseases, prostatic hyperplasia, smoking and excessive alcohol intake. 

The high androgen levels in women (mild to moderate AD) in low stress environments shows the altered metabolism of the androgens. The significant correlations between DHEA and cortisol, androstenedione and cortisol indicated that hormone production in the adrenal cortex of the kidneys were like that of younger people. In another study mentioned in this paper, associated high levels of cortisol and DHEA with cognitive dysfunction. There were higher chances of performing better with lower levels of DHEA. Later in the study, they had said that further investigation was required to assess the androgen and gonadal hormone metabolism as they had only reported increased basal androgen levels. In another study, they investigated the thyroid hormone levels in the cerebrospinal fluid (CSF – present to keep the brain afloat and washout any toxins) and find a correlation to the AD severity in patients with normally functioning thyroids. Thyroid hormone (TH) helps in metabolism in the brain and hence can be found in the CSF. There are several forms of TH – they are usually numbered as T_2, T₃, T₄etc. They used something called lumbar puncture to extract spinal fluid from people (sounds pretty painful!). They used highly specific techniques called mass spectrometry and high performance liquid chromatography to assess the CSF containing thyroid hormones. They had about 35 patients (9 males and 26 females, approximately 66 years). The CSF TH concentrations were representative of the blood TH concentration. The AD patients were diagnosed through CT scans, neuropsychological tests, MRI and Mini-Mental State Examination (MMSE). The control group had 10 subjects with normal cognitive abilities and normal MMSE. They had undergone lumbar puncture due complains of severe headaches. Exclusion criteria included thyroid problems, abnormalities of CSF routine analysis or any proof that the barrier between their blood vessels and brain was damaged by in depth analysis of the CSF. 

They used ELISA kits (used to detect and quantify proteins) to measure the beta-amyloid and tau, along with the TH. After processing, they injected the sample into the HPLC for analysis. T₄, T₃, rT₃ were detected in the HPLC. For the most part, there was no difference observed between AD and control groups. However, there was a lower correlation coefficient between CSF T₃ and blood T₃in AD patients as opposed to control. CSF TH and CSF beta-amyloid had no significant correlation. The absence of correlations showed the complex distribution of TH between blood and the CSF. . The same could be said for CSF T₄, T₃or rT₃between patients and controls. This was probably due to the fact that it was difficult to find controls who would want to opt for a lumbar puncture. They found significant negative correlations between rT₃, or rT₃/T₃ratio and MMSE only in AD patients. 

One main feature of music is that it can elicit a host of different emotions. Autobiographical memory is the long term memory that allows recovery of experiences and knowledge. One autobiographical component is emotion which is basically what helps remember certain memories than when emotions are not involved. Thus this current study tried to find a link between emotions and music-evoked autobiographical memories in AD. They asked the subjects to choose their favorite music as they hypothesized that favorite music hold high emotion valence. When asked about their favorite music, some were unable to name them and so their family helped out by naming it. After going through the conditions, they were asked for any details they remembered. They were rated using a TEMPau that measures autobiographical memory – zero for absence of memory and ranging up to a four for feelings, emotions, thoughts and perceptions. The emotions were categorized as positive or negative and rated accordingly. The results showed amazing results for the chosen condition: the controls scored an average of 4 as expected, but the AD patients had scored 3.33. Furthermore, they produced more positive words than negative, and hence the autobiographical memory relevant to it. 

In terms of data collection, they obtained basal levels of serum cortisol (adrenocortical), dehydroepiandrosterone (DHEA – an earlier form for androgenic and estrogenic steroid formation in tissues), androstenedione, estradiol (estrogen), sex hormone binding globulin, after an overnight fast at 8 in the morning. They did radioimmunoassay using radioactive labels to find the hormones. The main findings were that there was an increased morning cortisol level, higher DHEA and androstenedione in AD patients. Women with AD had a high level of androstenedione and DHEA after BMI and age was considered. There was a strong correlation between androstenedione and DHEA, and cortisol levels, unlike the control group. The most interesting fact is that the levels are this high in the early phase of AD, but it drops in the advanced stage. 

So why is this disease one of the most devastating ones and what does it look like on a neurobiological level? From a broader perspective, our brain only looks like a grey mush that may not be containing much. However, on a microscopic level, the sheer detail of how much goes on in there can be overwhelming. However, to make it simple, we will look at AD through two perspectives. Tau is a protein that in normal terms is actually there to be helpful. Our brain has microtubules that is necessary for transporting nutrients around the brain. The tau protein stabilizes those microtubules. However, by random mutation, this incredibly essential protein becomes a problem. It starts to entangle in parts of the brain that are responsible for memory, like the hippocampus. With the lack of nutrients, the neurons (nerve cells) in the brain start to die. Another vital player in AD is beta-amyloid. Beta-amyloid is the product of the precursor amyloid protein. Usually, the fluid in our brain (CSF) is able to wash out the amyloid build up. However, when it starts building up as plaques it can get to a toxic level, thereby causing cell death in the brain. With all this shrinkage, especially in the areas responsible for forming connections and making memory, it becomes increasingly difficult for people to remember details about their lives.