Delirium & Dementia - Clinical Case Series #4
Adapted by Prof. Henry O'Connell from "Evolution and Psychiatry: Clinical Cases" - Edited by Dr Gurjot Brar
Welcome to the fourth in our clinical case series, exploring common mental disorders through the lens of evolutionary psychiatry. A ‘problem-based learning’ (PBL) approach is taken with learning outcomes defined at the outset, followed by several clinical encounters with fictional scenarios, interspersed with theory responding to the learning objectives. This method has emerged globally in medical curricula and has a good evidence base in medical education promoting self-directed learning. We hope you enjoy this format and look forward to your feedback.
This case series will often refer to key principles defined in the following article published in July 2023 which serves as a primer:
Delirium & Dementia
Learning Objectives
Outline the key facts about delirium, relating to clinical features and diagnostic criteria, epidemiology, aetiology, pathophysiology and management. Are there any potential evolutionary perspectives on the condition?
Outline briefly the key facts about dementia, relating to clinical features and diagnostic criteria, epidemiology, aetiology, pathophysiology and management.
Outline the main evolutionary theories relating to ageing, including mutation accumulation (MA) and antagonistic pleiotropy (AP).
How can the evolutionary perspective be utilized to aid our understanding of dementia and other age related conditions?
Outline how the evolutionary perspective can be utilized in planning and delivering healthcare for older people.
‘This poor man is very confused’
Dr. Michael Flynn recently graduated from medical school and has just started his internship at St. Fintan’s Hospital. It is his first night on call with the surgical team and he is busy, running from ward to ward. He has multiple jobs to do, including taking bloods, inserting intravenous lines and charting medication for pain and sleep. Most of the patients he sees are elderly with both surgical problems and medical comorbidities. By 2 a.m. it seems that things have finally settled down and Dr. Flynn goes to the Doctors’ Residence to have a very late dinner. Halfway through his meal, he receives yet another call. It’s one of the nurses on the Orthopaedic Ward: ‘Dr. Flynn, we need you to come urgently. We have James Murphy here, an 85 year old man with dementia who was brought in from a nursing home two days ago after falling and sustaining a neck of femur fracture. He was operated on immediately and he is now 24 hours post op. He was fine initially, but now he’s become very agitated, screaming and shouting and trying to pull out his urinary catheter. This poor man is very confused’.
Dr. Flynn rushes to the ward where he gets some more information from the nurses about the patient’s baseline cognitive status and medical comorbidities. He then goes straight to the patient’s bedside and begins to assess his mental state and perform a physical examination. He tries to reassure and calm Mr. Murphy, who is clearly very disorientated and frightened.
Dr. Flynn calls the Registrar ten minutes later with his key findings: ‘Mr. Murphy is an 85 year old nursing home resident who is 24 hours post repair of fractured neck of femur, with background diagnoses of Alzheimer’s Disease, Rheumatoid Arthritis for several years and Colorectal Carcinoma ten years ago. He is currently disorientated, highly agitated and inattentive, unable to complete the months of the year backwards test. He appears to be septic, with a temperature of 38.5 and his urinary catheter is the most likely source of infection’.
On the advice of the Registrar and with the help of Nursing staff, Dr. Flynn removes the urinary catheter and starts Mr. Murphy on broad spectrum intravenous antibiotics and analgesia. He also charts him for low dose Haloperidol that can be given orally or intramuscularly. Later on as he writes up the clinical notes, one of the nurses asks if he will give a brief explanation to the student nurses of the key clinical facts relating to delirium and dementia (See Learning Objectives 1 and 2).
Learning Objective 1:
Outline the key facts about delirium, relating to clinical features and diagnostic criteria, epidemiology, aetiology, pathophysiology and management
Delirium is a severe and complex neuropsychiatric disorder. Along with the core cognitive feature of inattention, patients may also have variable levels of disorientation, memory impairment and psychotic symptoms such as hallucinations. The clinical picture may fluctuate significantly in the same episode between hyperactive and hypoactive manifestations, the former involving agitation and behavioural disturbance and the latter involving withdrawal. The course is typically acute in onset with a fluctuating course and, although sometimes difficult to identify, there should be an underlying physical cause such as infection or pain.
Up to 20% of general hospital inpatients develop delirium at some point on their inpatient journey, with even higher impacts (up to 90% of patients) in palliative care settings. Risk factors for delirium include older age, medical comorbidities, polypharmacy and underlying cognitive impairment or dementia.
Delirium is associated with multiple adverse outcomes such as increased length of stay in hospital and increased risk of subsequent mortality. Therefore, accurate and timely detection is essential. Treatment involves identifying and managing the underlying cause, environmental measures aimed at orientation and the judicious use of low dose antipsychotic drugs (O’Connell et al, 2014).
In view of its universality and high prevalence in medically unwell patients, the question arises as to whether delirium is an evolved response to major physiological insults and illness. This can be seen as analogous to the model put forward by Raison and Miller (2017) on the evolution of depression as a manifestation of pathogen-host defence. Drawing from this model, there are many potential areas of overlap between delirium and depression, including some of the clinical features and behaviours, such as depressed mood, withdrawal, agitation and inattentiveness, especially in hypoactive delirium.
Learning Objective 2:
Outline briefly the key facts about dementia relating to clinical features and diagnostic criteria, epidemiology, aetiology, pathophysiology and management
Dementia refers to a wide range of age related neurodegenerative disorders. Alzheimer’s Disease accounts for approximately two thirds of cases, with Vascular Dementia accounting for 20-25% of cases. Rarer forms such as Frontotemporal Dementia and Dementia with Lewy Bodies account for 5-15% of cases. There may also be overlap in terms of underlying pathology, especially between Alzheimer’s and Vascular aetiology.
Clinical features include cognitive difficulties with memory, language and orientation. Changes in personality may also occur, along with behavioural and psychiatric features such as apathy, withdrawal, agitation, wandering, aggression and psychotic symptoms. The clinical features vary widely depending on dementia subtype and even between individuals with similar underlying neuropathology.
Incidence and prevalence rates rise steadily with age, with 5% of those over age 65 having dementia and up to 20% of those over age 80. Assessment and diagnosis should involve careful history taking, neuropsychological testing, neuroimaging and a full physical review to outrule potentially reversible cause of cognitive impairment such as hypothyroidism or normal pressure hydrocephalus. Aetiology is multifactorial and includes genetic factors with multiple genes being implicated, vascular risk factors and history of head injury. Although 5-10% of dementia cases arise before the age of 65, advancing age is the single most important risk factor.
Currently available medication treatments include the acetylcholinesterase inhibitors and Memantine. These medications may provide some symptomatic benefits in the short term but they are not disease modifying. Other aspects of treatment may include management of behavioural and psychiatric symptoms with other psychotropic medications (e.g. antipsychotics and antidepressants) and environmental measures. Dementia is by definition progressive and irreversible with survival rates ranging from 5-15 years from diagnosis. Progression to intensive home-based treatment long-term nursing-home care is common in severe dementia. The reduced cognitive reserve of dementia means that sufferers are at increased risk of developing delirium (See Learning Objective 1) in the context of physical illness and physiological stressors.
‘Those unfortunate Struldbruggs…’
It is almost 5 a.m. by the time Dr. Flynn gets back to the Doctors’ Residence. It’s been a busy night for the medical and surgical teams and three other junior doctors have also just got back from the wards and are having tea. The Registrar calls to Dr. Flynn: ‘Well done on your management of that elderly man. Come and have some very late - or maybe it’s very early - tea with us’.
With everyone a little giddy from sleep deprivation and the stress of the night just gone by, the group starts a wide ranging philosophical discussion about the reasons why people get sick and the fact that most of their patients seem to be elderly. ‘Ageing is a scourge, I tell you’, says the Registrar. ‘Look at your elderly man earlier, Mike. He has Dementia, Delirium, a broken hip, Rheumatoid Arthritis and Colorectal Cancer. It seems to me that if you live long enough you will get every disease known to mankind. The elderly are like those unfortunate Struldbruggs who Gulliver discovered on the island of Luggnagg on his travels (reference). They had eternal life but they got older and sicker for eternity. Now that’s what I call a double edged sword’.
Then the medical intern joins the conversation: ‘Sometimes I wonder why we age at all. I mean, what are the processes behind it?’ (See Learning Objective 3) And sometimes I feel that we as doctors have a hopeless task. Children and younger people seem to recover quickly from illness and surgery. But when treating older people the hidden enemy is not the illness itself but ageing. And when it comes to fighting a war against ageing, well you might as well be King Canute commanding the sea to turn back’.
Another doctor then joins in: ‘Ageing is a relentless and merciless process. And yet the ageing journey is so different for different people, and it doesn’t always seem to be based on their lifestyles either. Sometimes I wonder if ageing is due to your wild youth catching up with you. But then some people seem to get lucky and others get very unlucky. Whatever the underlying processes, ageing is inevitable. Look at us, for example. Poor Dr. Flynn here looks a lot older than when he started his shift only yesterday!’
(See Learning Objectives 3 and 4)
Learning Objective 3:
Outline the main evolutionary theories relating to ageing, including mutation accumulation (MA) and antagonistic pleiotropy (AP)
In considering evolutionary aspects of ageing, it is useful to start with the key evolutionary principles for illness outlined earlier:
Randolph Nesse’s Six Evolutionary Reasons why Bodies/Minds are Vulnerable to Disease
Which can also be grouped into three pairs, with the first two arising because of the slow pace of evolution, the second pair arising because of the imperfect nature of evolution and the last pair arising because of the fact that evolution is not interested in our happiness or well-being and that symptoms, while unpleasant, do not always indicate disease or disorder.
Mismatch: our bodies are unprepared to cope with modern environments.
Infection: bacteria and viruses evolve faster than we do.
Constraints: there are some things that natural selection just can’t do.
Trade-offs: everything in the body has advantages and disadvantages.
Reproduction: natural selection maximizes reproduction, not health.
Defensive responses: responses such as pain and anxiety are useful in the face of threats.
The first two principles, relating to evolution being a relatively slow process in humans and thus leaving us prone to disease because of mismatch with modern environments and the relatively far speedier evolution of microorganisms, are not of clear relevance to the phenomenon of ageing.
The next two principles, relating to the ‘imperfection’ of evolution, are of more relevance to ageing. In particular, the principle of ‘trade-offs’ is potentially of relevance in conceptualizing ageing and age related health conditions. Specifically, genes associated with characteristics and traits that are beneficial in our younger years and improve our chances of reproductive success may prove to be damaging to our health and well-being in later life. This particular phenomenon is known as ‘Antagonistic Pleiotropy’.
Regarding the last pair of principles, of most relevance to an evolutionary perspective on ageing is the concept that evolution is focused on maximizing reproduction and not health or well-being. As such, natural selection does not operate on genes that are associated with ageing. Likewise, it may be that there is selection against anti-ageing genes.
Other important principles to consider include those seen in laboratory situations with other species. For example, artificial selection for longevity in fruit flies and flour beetles is associated with reduced fecundity and vice versa.
More ‘proximate’ explanations for the ageing process include mutation accumulation over the lifespan along with reduced immunological competence and reduced tissue repair capacity.
In considering evolutionary aspects of ageing and age related health conditions, the concept of Viewing Diseases as Adaptations (VDAA) should also be borne in mind. For example, although I have outlined in Learning Objective 1 above how delirium may be part of an evolved ‘illness’ response to physiological threats, it is unlikely to be of adaptive benefit in itself and may in fact represent a maladaptive manifestation of a ‘normal’ sickness response.
Learning Objective 4:
How can an evolutionary perspective be utilized to aid our understanding of dementia and other age related conditions?
A number of different phylogenetic phenomena must be taken into account when considering evolutionary perspectives on dementia.
The first of these relates to the dramatic increases in brain size seen in pre-human hominid and ultimately human species since our branching off on the evolutionary tree from chimpanzees approximately 7 million years. The relatively gigantic human brain (in comparison to that of other primates) is immature at birth and goes on growing and developing at intrauterine levels for the first year of life, in comparison to other primates in whom brain development is near completion at the time of birth.
If human gestation was prolonged to accommodate the fuller growth and development of our large brains to near completion at birth as in other primates, safe delivery would not be possible. Even as it currently exists, human birth is a dangerous process for both mother and infant, because of the narrow fit of the infant’s head within the birth canal.
Following this dangerous entry into the world, the human infant continues in an immature state requiring intensive nurturing for the first years of life, especially the very first year. This puts huge time and energy demands on mothers in particular. The fact that human females live for a number of decades post-menopause (unlike other primates) means that grandmothers are present to help in supporting mothers and raising offspring. In evolutionary terms, this is referred to as the grandmother hypothesis.
The next phenomenon to consider is the fueling of our large brains. The energy demands of our brains are most efficiently met by meat eating, and we eat relatively more meat than any other primate. However, along with the very significant energy benefits of meat eating, downsides of this dietary choice may include cardiac and vascular disease. And this is where ApoE genotype comes in. It appears that ApoE3 and ApoE2 genotypes may have emerged from a progenitor ApoE4 phenotype in conjunction with increases in human brain size. As ApoE3 and ApoE2 status appear to be protective against vascular disease and ApoE4 (especially in the homozygous state) is associated with increased risk of cardiovascular disease and dementia, the emergence of ApoE3 and ApoE2 may have occurred to ‘facilitate’ our carnivorous fueling of our large brains.
The phenomenon of Antagonistic Pleiotropy (AP) is also likely to be of relevance to evolutionary formulations on dementia. Therefore, research questions should focus on identifying genes and characteristics that confer reproductive benefits in younger life but ‘turn rogue’ and are associated with ageing and dementia in later life. Perhaps the most dramatic example here is seen in the genetics of Huntington’s Disease. Homozygous individuals are guaranteed to develop this devastating condition in middle or later life, although it remains silent during the reproductive years.
‘We have concerns about this man’s care’
Dr. Flynn is back on call four days later. It is a much quieter night and he manages to have dinner in the Doctors’ Residence at 6 p.m. and then watch a film on television. It’s so quiet that he decides to do a walk around the wards, just to make sure that all is well and that his bleep is not malfunctioning. He calls to the Orthopaedic ward first. One of the Nurses approaches him and tells him that Mr. Murphy is doing very well. His delirium and urinary tract infection have settled and he is quite content on the ward. In fact, there is a plan for him to be discharged back to his nursing home the next day.
‘But since he came in’, the nurse begins, ‘There have been a few issues raised about his care in the nursing home. I noticed what could be old bruises on his upper arms, like he was being handled roughly. And his feet and toenails have not been tended to for weeks. And I wonder why he was wandering alone when he fell and sustained that fracture. We will talk to the Social Worker in the morning before there’s any plan for him to return to that nursing home. We have concerns about this man’s care’.
Learning Objective 5:
Outline how the evolutionary perspective can be utilized in planning and delivering healthcare for older people
The ageing of populations worldwide, especially in the western world, is associated with inevitable increases in the prevalence of dementia and other age related conditions. Improved medical and social supports also means that people with age related conditions are living longer than ever before. Therefore, conditions such as dementia are already hugely costly for healthcare services and such cost is likely to increase substantially in the coming decades. Governments and healthcare providers must acknowledge not only current demands and shortfalls but also provide for future years.
At an individual level, caring for older people is unique to our species among other primates. An ‘inversion’ of intergenerational caregiving takes place with dementia care and elderly care generally. This inversion is often extremely demanding both physically and emotionally, whether the elderly person being cared for is a relative or not. This stress should be acknowledged and incorporated into healthcare worker training and education. Unless acknowledged, stressed and overworked healthcare workers are at risk of neglecting and potentially abusing those in their care.
Further Reading:
Chapter 17 - Alzheimer’s Disease as a Disease of Evolutionary Mismatch, with a Focus on Reproductive Life History - Evolutionary Psychiatry Current Perspectives on Evolution and Mental Health
Fox M. (2018). 'Evolutionary medicine' perspectives on Alzheimer's Disease: Review and new directions. Ageing research reviews, 47, 140–148. https://doi.org/10.1016/j.arr.2018.07.008
Gunten AV, Clerc MT, Tomar R, John-Smith PS (2018) Evolutionary Considerations on Aging and Alzheimer’s Disease. J Alzheimers Dis Parkinsonism 8: 423. DOI: 10.4172/2161-0460.1000423
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