The heart supplies blood to the brain, so cardiovascular disease can be associated with cerebrovascular disease and vice versa. That said you can have them as separate entities as well. There isa huge body of literature on how disorders associated with the cardiovascular system (i.e. hypertension, hyperlipidemia) are associated with vascular dementias- good study cohort was the Honolulu Asian Aging Study- or HAAS. Also a side note with lesions, It is all about location; location will typically dictate the functional deficit. So you can have infarcts which are more associated with a vascular Parkinsonism (say if it is in the striatum), or an infarct can be associated with a cognitive deficit (more in a limbic area). Which explains why you can get soo many different phenotypes with infarcts.

Thank you Brittany, that makes a great deal of sense with regards to phenotypes and is extremely helpful.

things can be very confusing (I've just started to delve into this lit as well), and another note - always be aware of "time" when reading some of the primary literature, so one of the going theories is that in midlife cardiovascular risk factors increase the risk of dementia- but then once a person has dementia they decrease.

I agree Brittany, it is most confusing. I am working specifically on Treatment Resistant Depression, in relation to lesions and cognitive processing dysfunction.

I have noted from various studies that micro and macro vascular lesions in strokes have shown significant correlations to unipolar depression symptomology after the cerebrovascular event, but it is not always possible to detect them. Lesions that can be detected (based on correlational evidence) have been linked to the triggering of Depression. For instance in Cerebral Ischemia they have found that Depression may be triggered in patients who have no previous history of Depression. They have termed it Vascular Depression. (It is noted that this suggests an underlying genetic susceptibility to Depression which remains latent until the occurrence of a physiological event).

The fact that Lithium (which promotes neurogenesis) is often a component of pharmacotherapeutic drugs used, amongst other things, for Treatment Resistant Depression (and other forms of Depression), Ischemia and the treatment of tauopathies (also a form of lesion), suggests the possibility of links. When considering the micro lesions that can occur, and may not be easily detectable, and can continue to occur in stroke patients, I ask whether there may not be a link between tauopathy, micro/macro lesions and Depression (sorry, it does seem to be a large leap, but I cannot find any evidence stating that tauopathy may not be involved in some measure, if you are aware of any please let me know). I have not found any studies in this regard and I question what impact this could have on the cognitive functioning of patients, and whether this may not present with different cognitive processing symptoms.

From that point I then wonder if there are not clusters of cognitive symptomologies ( ie., a specific one for Treatment resistant Depression, and another for Dysthymia) that, depending on these kinds of physiological factors will be similar, but have different dominant dysfunctional processes. If there were different dominant processes, we may be able to predict, firstly what the pattern of lesions are that contribute to the occurrence of Depression. Secondly, when presented with a patient who appears to have a certain type of lesion, or lesions, if we know what the cognitive symptomology is, we may be able to predict where micro lesions could be occurring.

Bearing in mind that tauopathy appears to affect the pre frontal lobes, that Depression involves dysfunctional cognitions, such as rumination, dysfunctional planning, inhibition/control/strategies/sadness/selective attention and so forth, and lesions in the pre frontal lobe disrupt various aspects of physical, cognitive and emotional processing (other parts of the brain are naturally known to be involved in affective disorders) the final question I came down to was, is Treatment resistant Depression possibly a form of neuro-degenerative disorder that involves micro and/or macro lesions in CVD/CBVD patients. Treatment resistant depression may be higher in cerebrovascular/cardiovascular patients with lesions, thus understanding lesions and possible differences is important for me, in particular the possibility of a cluster of specific cognitive symptomology and this is one of two projects I am working on as an area of focus for a PhD.

If you have any information in this area, or able to correct any of my knowledge Brittany, it would be much appreciated - sorry this post was long, I have tried to shorten it and hope I have not left out aspects that affects the clarity of the communication. If anyone else has any knowledge in these areas, their learned input would also be appreciated.

Cheryl: it is somehow well stablished, with few negative findings, that CVD lesions, in particular those located at the pre-frontal cortico-subcortical circuitry, is associated with refractoriness in major depression. These patients usually presents with significant cognitive impairment, mostly in executive functioning.

I would be more careful with the relationship between depression, taupathies and refractoriness. There is no study, to my knowledge, that specifically linked major depression and Tau protein pathology.

Also, lithium can exert its therapeutic effects in these patients by mechanisms beyond stimulation of neurogenesis. Lithium can reduced the activity of GSK-3B enzyme, reduce oxidative stress markers, and stimulate the synthesis and release of neurotrophic factors.

Thank you so much Breno, your expertise is greatly appreciated and invaluable. You have answered my question precisely and have cleared up some confusion for me with regards to CVD lesions and also the actions of lithium. I have not been able to find any research on the possible existence of tauopathy in major depression and it also helps that someone is able to verify that there does not seem to be any. Thank you once again!