Working in memory clinic setting, apathy and depression are quite complex to handle, because they can appear in the very beginning of MCI and the patients tend to drop out from treatment.

I work in a dementia assessment unit for people with moderate to severe dementia. It is my belief that the neuropsychiatric symptoms that causes the admission when family members can no longer cope and I believe that these symptoms do no appear until much later in the progression of the disease and the cognitive impairment is severe.

The symptom are quite common and epidemiological studies support a conversion rate between 15% to 30 %.  Review the following papers by Morris and Petersen:

And review: Alzheimers Dement. 2013 May;9(3):310-317

Mild cognitive impairment in a community sample: the Sydney Memory and Ageing Study.

Brodaty H, et al.

http://www.ncbi.nlm.nih.gov/pubmed/23110866

The question you raised is a very important one, much more when recently, the new DSM5 has changed the denomination and the diagnostic criteria for MCI (now called Mild Neurocognitive DIsorder). Our group have large experience in this field and we have previously publicated some population-based studies in this subject.

There is many ways to assess NPS (the NPI is, largely, the most used) but mucho or them are not exempt of problems. We have partially solved some of them, at least at a population level, using the symptoms present in the Geriatric Mental State, which provided us accurate information about much more symptoms than other interviews and are less contaminated by the caregiver's opinion.

Please, let me recommend some of our papers:

• http://www.ncbi.nlm.nih.gov/pubmed/24893954
• http://www.ncbi.nlm.nih.gov/pubmed/19073431
• http://www.ncbi.nlm.nih.gov/pubmed/19053966

I hope you find it useful.

Alois Alzheimer did not really explore social circumstances  or very much and the paper, must dig out the ref for you, was very short and focused on plaques and tangles. The large nun study demonstrated that not everyone who has plaques and tangles has dementia. Obviously as people develop the brain condition the behaviour may change as with stroke they can be limited in making choices and expressing their identity. I also think the reactions to them by others i.e constantly checking for deficits tests MMSE and negatively positioning them contributes to behaviour change, as we fail to explore identity as a single phenomenon at point of diagnosis.

A very interesting question and it certainly the case that people who we treat for seemingly intractable functional mental health difficulty then often go on to develop cognitive difficulty although the chronic stress and psychiatric treatments they've experienced probably impact on this.  However, its my understanding of the literature that it is increasingly difficult to think of MCI as a single clinical presentation and that the relationship to the development of subsequent dementia is not linear - I thought the field was generally moving away from the assumption that MCI is necessarily a prodrome for DAT

kind Ricardo,

the problem of BPSD in MCI is relevant indeed, since the beginning.

Here follow an example of their impact in a longitudinal observation:

Int J Geriatr Psychiatry. 2012 Feb;27(2):197-204. doi: 10.1002/gps.2709. Epub 2011 Mar 29.

Neuropsychological screening performance and the association with activities of daily living and instrumental activities of daily living in dementia: baseline and 18- to 24-month follow-up.

Monaci L, Morris RG.

SourceWolfson Neurorehabilitation Centre, St Georges' Healthcare NHS Trust, London, UK. [email protected].

Abstract

OBJECTIVE: The use of neuropsychological assessment beyond diagnosis is related partly to the extent to which it can indicate everyday function. This study investigates whether the associations between neuropsychological functioning, activities of daily living (ADL) and instrumental activities of daily living (IADL) change over an 18- to 24-month follow-up, exploring whether these change with dementia progression.

METHOD: Thirty-four patients with probable Alzheimer's disease were assessed at baseline and again after between 18 and 24 months. Neuropsychological function was assessed using the revised Cambridge Cognitive Examination, which includes in it the Mini mental state examination and an executive functions scale. ADL and IADL were also measured, together with background neuropsychiatric features by using the Neuropsychiatric Inventory.

RESULTS: Pearson correlations between the measures of daily functioning and cognitive abilities and neuropsychiatric symptoms showed that initially neuropsychological test results tended to correlate with IADL rather than ADL measures. Neuropsychiatric symptoms were not correlated whether IADL or ADL. At follow-up, none of the neuropsychological function measures correlated with IADL or ADL, but neuropsychiatric symptoms were correlated with IADL.

CONCLUSIONS: At baseline, neuropsychological function is associated with IADL but not ADL. At follow-up, the association between neuropsychological function and IADL diminishes, and associations between neuropsychiatric disturbances and IADL emerge.

Relationship between Neuropsychiatric symptoms (NPS) and Mild Cognitive Impairment is a very intriguing matter. First of all, there is a causality problem. Up to day, it is not sure if NPS in MCI are cause or consequence of a neurodegenerative disorder (though some studies point out that resistence to pharmacological treatment to some NPS as depresion can be seen as a result of NPS are more consequence than cause). This is not a trivial matter because pharmacological treatment to depresion can have paradoxical effects in dementia progresion.

With respect to that conversion ratio increases in MCI patients with depresion, there are some shadows too, because depresion prevalence is higher in MCI subtype with higher conversion ratios to Alzheimer disease (i. e., amnestic MCI). Adding fuel to fire, depresión and apathy frequently are confounded, and some studies found that apathy predicts better conversion rates (in line with early signals of cognitve impairment in executive functioning).

dear all, the answer by Arturo Pereiro is intriguing

hence, let me paste here 3 steps I posted elsewhere in ResearchGate, about the relationships about depression & dementia / (prodromal) cognitive decline

I can attempt an answer at 3 levels:

1) clinical level

Jesùs Porta-Etessam in the IDEAL Study reported that in moderate AD patients depressive symptomatology [Cornell Scale for Depression in Dementia >= 8] is associated with excessive neurospychiatric symptoms and functional - but not cognitive - 6 month deterioration [Alzheimer Dis Assoc Disord 2011; 25: 317-25]

2) epidemiological level

in the Healt & Retirement Study, Jajodia & Borders found amng 14.000 people older than 50 that memory performance predicted change in depressive symptoms 2 years later (not vice-versa); including vascular health variables diminished the size of the observed relationships, pointing at a possible partial explanation by biological processes of the effect of memory on mood [the Journasl of Gerontology Series B 2011; 66(5): 571-81

3) biological/clinical level

Amyloid-associated depression may define a subtype of depression representing a prodromal manifestation of AD, associated with greater impairment in meory, visuospatial ability and executive function, compared to those without depression and to nonamyloid depression, among homebound elderly individuals [Arch Gen Psychiatry 2008; 65(3): 542-550

best regards, Mauro Colombo

Perhaps how and when the information about the NPS is collected is a key.

There is a lot of environmental factors in this information, stress, family issues, the ontology of each individual and the background of the observer. I found, just as an example, many NPS in dementia patients with serious problems of drug addiction among their sons and grandsons (even if they don´t live together. And they refer this as a core problem in their lifes, more than the dementia and NPS itself.

 Also in my experience, in agreement with some of the above observations, the neuropsychiatric symptoms can be present in more than half of the MCI patients as reported in the literature(Lyketsos et al 2002), more frequently apathy and depression (Di Iulio et al 2010), especially founded in the "converters" MCI (Robert et al 2006). MCI classification in subtypes, also under the view of neurospychiatric semeiology (to  obtain also with collaborative informants), could help us to better understand the underlied pathologies and prognosis of our patients, together with neuroimaging , biochemical and genetic data   

The issue of NPS in MCI and more advanced forms of dementia is indeed intriguing. My area of interest is the connection between diet and brain function. Over the past 3-4 decades we have experienced a dramatic increase in virtually all common brain disorders, yet the scientific community has yet to come up with a plausible explanation for this obvious epidemic. 

We now believe that our modern diet of highly processed food is driving much of this pathology. The incidence of common metabolic disorders like insulin resistance, obesity and type II diabetes seems to mirror the increase in theses brain disorders. I suspect that both are driven by our pathological diet. Humans never ate this type of food until the past 40-50 years. Look around you and the effects are obvious.

We now call this form of food induced brain dysfunction Carbohydrate Associated Reversible Brain syndrome or CARB syndrome. If people manage to change their diet to consuming whole foods, the pathology seems to be reversible.

If you combine any form of dementia with CARB syndrome, it's like adding gas to a fire. Alzheimer's disease tends to be very slowly progressing disease in countries that still consume a healthy diet--like Greece. In Greece it's typicality a 30 year disease. In the US it's a 10 year disease because most people with Alzheimer's disease also have CARB syndrome.  I blog about this topic at:

http://carbsyndrome.com/

Quite interesting and it does make sense, like the old say "you are what you eat".

However,  don't forget the aging epidemic that also adds to the formula. Since there is an emerging number of older individuals every year there will be a growing number of geriatric diseases. Neverless; growing old doesn't have to mean getting sick and that is the fine line that is not clear.

Thanks for bringing some unconventional thoughts to the discussion.

Patricia--Again for many people diet determines what happens to them as the age and how fast they age. We have a home in Greece and over there Alzheimer's disease tends to progress very slowly over 30 years or more. These patients tend not to have a lot of NPS. 

In this country Alzheimer's tends to be a 10 year disease and these patients often do have NPS often early in the course of the disease. In my opinion that's because they usually have two diseases--Alzheimer's disease and CARB syndrome. Adding in CARB syndrome is like throwing gas on a fire.

For all of these patients I recommend measuring a AA/EPA ratio and then supplements with a high quality omega 3 fatty acid:

http://www.drsears.com/resources/cellular-inflammation-testing/

Along with eating a healthy whole foods diet this approach will slow down dementia, suppress NPS and reverse CARB syndrome.

In the Women's Health Initiative Memory Study (see Colenda et al Am J Psychiatry 18: 177-186, 2010), 18% of post-menopausal women had at least one psychiatric disorder, with depression being the most common.  When depression was present, there was usually also impaired cognition (MCI or dementia). 

Article Psychiatric disorders and cognitive dysfunction among older,...

Once again, Linda Hershey underscores a relevant issue, that reminds us to the give attention to females' problems, not only during march the 8th, as today

Mauro Colombo

kind Ricardo

I intercepted your question about depression and its possible role as risk factor for dementia - maybe through MCI - but the question disappeared from my laptot while uploding the following document: i hope this alleged fits your request, Mauro Colombo

thanks Mauro, I'm going to check this out and it will surely clarify some issues.

I agree Lawrence and I believe that Alzheimer's original research did not investigate deeply enough the social circumstances of Auguste D. In addition, though I am not a doctor I feel that the individual's immune system, maybe even the liver play a part.

In other words: We don't know what causes AD.

Virginia--I agree with your perspective. Even though we don't really understand the cause of AD, we do know what seems to prevent it or makes it worse. Eating a pro-inflammatory diet of highly processed food clearly accelerates the disease. I see this every day in my patients.

We also know that high quality omega supplements can possibly prevent or slow down AD if they are started soon enough and given in a high enough dose. My friend Barry Sears has been saying this for years and I agree with him.

Countries like Japan have a relatively low incidence of all forms of dementia and other  common chronic diseases tend to eat a diet low in highly processed food and high in omega 3 fatty acids.

The same is true for mild cognitive impairment and neuropsychiatric symptoms. We don't necessarily have to know what causes a disease to effectively prevent or treat it. We really don't understand the cause of type II diabetes although theories abound, yet we do know to prevent it or reverse it if it is caught soon enough.

http://www.emaxhealth.com/1020/omega-3-fatty-acids-offer-potential-new-alzheimers-treatment

Here is more support for the fact that diet plays a role in Alzheimer's expression. Some suggest that fat is a risk factor but we now believe that it's the type of fat that counts. There is evidence to suggest that a high fat ketogenic diet is neuroprotective. Of course this only works if you eat healthy fats like omega 3 fatty acids, olive oil, coconut oil but not saturated fats or omega 6 fatty acids added to highly processed foods.

http://www.sunarc.org/JAD97.pdf

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2367001/

How can we talk about the risk factors in AD when we have no idea what causes it?

There are another contributions to our so discussed topic. Thanks to all for so important information.

Background Affective and emotional symptoms such as depression, anxiety, euphoria, and irritability are common neuropsychiatric symptoms (NPS) in pre-dementia and cognitively normal older adults. They comprise a domain of Mild Behavioral Impairment (MBI), which describes their emergence in later life as an at-risk state for cognitive decline and dementia, and as a potential manifestation of prodromal dementia. This selective scoping review explores the epidemiology and neurobiological links between affective and emotional symptoms, and incident cognitive decline, focusing on recent literature in this expanding field of research. Methods Existing literature in prodromal and dementia states was reviewed, focusing on epidemiology, and neurobiology. Search terms included: “mild cognitive impairment,” “dementia,” “prodromal dementia,” “preclinical dementia,” “Alzheimer's,” “depression,” “dysphoria,” “mania,” “euphoria,” “bipolar disorder,” and “irritability.” Results Affective and emotional dysregulation are common in preclinical and prodromal dementia syndromes, often being harbingers of neurodegenerative change and progressive cognitive decline. Nosological constraints in distinguishing between pre-existing psychiatric symptomatology and later life acquired NPS limit historical data utility, but emerging research emphasizes the importance of addressing time frames between symptom onset and cognitive decline, and age of symptom onset. Conclusion Affective symptoms are of prognostic utility, but interventions to prevent dementia syndromes are limited. Trials need to assess interventions targeting known dementia pathology, toward novel pathology, as well as using psychiatric medications. Research focusing explicitly on later life onset symptomatology will improve our understanding of the neurobiology of NPS and neurodegeneration, enrich the study sample, and inform observational and clinical trial design for prevention and treatment strategies.

Sorry. The abstract posted below is from our job:

Affective and emotional dysregulation as pre-dementia risk markers: exploring the mild behavioral impairment symptoms of depression, anxiety, irritability, and euphoria

Hello!

Generally speaking, psychiatry suffers of a poor and variable definition of illnesses. Precise studies of specificity, predictive values and, above all, sensitivity lack sorely. Therefore, it's almost impossible to assess what is, or not, part of an illness.

Cognitive impairment is not always due to a limited dementia and Alzheimer's disease is not the only cause of dementia. Equality: cognitive impairment = dementia = Alzheimer's is, at least, unreasonable, but frequently used, especially by GPs.

Depression is, nowadays, limited to psychic features. Neurologic and somatic ones have been forgotten. It implies frequently cognitive impairment and, not so rarely, pseudo-dementia, which is reversible with an appropriate treatment.

Mistake with Alzheimer's is frequent, approximately 1/3 in my experience of gastroenterologist interested by depression!

Conversely, depression, a syndrome and not an illness, is frequently associated (why?) with other illnesses, from pancreatic cancer to Parkinson's disease.

Association with Alzheimer's is not rare, frequently underrated and, even more, under-treated.

It is as more regrettable than it's a major factor of suffering of the patient and his entourage.

Moreover, taking into account the low efficiency of Alzheimer's treatment, if present, it is be the best way to improve situation, much better than neuroleptics "to have peace".

indeed, a misleading may come from the trade name of a famous neuroleptic that reminds "piecegiving" ... Mauro