Alan mentioned that strange nocturnal events from Ann were wearing him down: wandering in the house at night, sometimes taking a picture down, sometimes falling on the floor and refusing to get up. He thought Ann had been drinking more alcohol than usual. She had bursts of inexplicable anger. I told him this was “sun-downing” where a fugue-like state can occur with no memory of it in the morning.
A crisis occurred three months ago. Ann, who had refused to stop driving to the gym and local shops, had a serious traffic accident. She drove through a red light and crashed her car as well as the car crossing on the green light. The insurance company covered the cost. But Ann has now forgotten the details of that event – or has re-arranged it in her mind. She was furious and insisted on continuing to drive with no insight into the calamity that could occur. She then talked about ending her life since she was no longer independent.
The Sheldon Chumir geriatric psychiatry team who saw Ann after her accident suggested mirtazapine 7.5-15 mg for its sedative and anti-depressant properties but were required to inform the police of the diagnosis. Ann merely saw this as an interference – still with no insight into the dangers of her driving – or indeed insight that there was anything the matter.
She currently requires companionship, and Alan has caregivers coming in two days a week. Ann has recently had a review at a specialist clinic including assessment of her capacity and her ability to look after her finances. This was handled with great sensitivity and skill by the staff there. Personal directives and an enduring power of attorney have been signed over to Alan.
AD is an evil disease. It robs humans of their personality, their individuality, their self-confidence, their reason, their emotions. Alan was finding it hard to adapt to this new person he was living with. Treatment is symptomatic at best. Drugs have been disappointing. Choline-esterase inhibitors such as Aricept may slow progress in some cases, but it caused Ann to have nausea and agitation. AD is a perfect disease for the fraudsters, grifters, mountebanks, quacks and blood-suckers of the Internet feeding on the sufferers of this nightmare of a disease.
We know so little of the causes – likely multifactorial – of AD. The impairment of cognitive functions has traditionally been thought to result largely from a reduction in neuronal and synaptic activities, and ultimately neuronal cell death, with the peptide amyloid-ß playing a role in pathogenesis – a cascade of events associated with excessive deposition of amyloid-ß – but is it cause or effect?
The genetics are unclear – better understood in the early-onset form (comprising <1% of cases), which typically follows an autosomal dominant pattern with gene mutations altering beta-amyloid metabolism to form intra-cerebral plaques. The genetics of later-onset AD (age 65 and older) are more complex, possibly with in-born errors of neuro-metabolism conferring susceptibility through more common but less penetrant genetic factors, for example, apolipoprotein E alleles allowing accumulation of intra-cerebral beta-amyloid. However, not all cases of human AD have observable plaques of beta-amyloid deposition nor, if present, does the amount of beta-amyloid present easily correlate with symptoms.
Another molecular mechanism of neuronal and synaptic disruption involves build-up of Tau protein filaments. This protein normally stabilizes neuronal microtubules, but in some dementia cases these proteins clump together forming long filaments of neuro-fibrillary “tangles” disrupting the neurone’s intercellular communication.
Is there a lack of an unknown vitamin or other food component? The dementia associated with excessive alcohol intake might suggest poor diet is a factor here. The MIND diet, based on a Mediterranean diet with plenty of greens, fish and olive oil and even a glass of red wine, seems, in a recent study, to slow the progress of AD.
Is there a transmissible factor, a “prion?” Prions are robust, hard-to-denature, misfolded protein molecules that can gain entry into cerebral tissues and are able to trigger and transform wild-type proteins into prionic forms by prion/protein-protein interactions forming plaques that interfere with neural circuits.
Kuru, a now-rare dementia in New Guinea, was likely caused by a prion from contaminated human brain tissue among natives who practiced a form of cannibalism in which some participants ate the brains of the dead as a funeral ritual.
The late Ralph Klein, usually a sensible man, said (jokingly) in the middle of the 2003 mad cow disease crisis in the UK that all a rancher had to do instead of slaughtering the herd was to “shoot, shovel and shut-up.” Canada can be a country that’s irony deficient at times – and this “advice” sent shivers down my spine – just one pre-clinically infected cow might allow penetration of bovine spongiform encephalopathy (BSE) prions into the food supply. (This has never been shown to occur in North America.)
Scrapie, a transmissible spongiform encephalopathy thought likely involving ingestion of prions, is a neuro-degenerative disease of sheep and goats. I recall in Scotland smart restaurants serving up “sheep’s heid” and “brain cakes” as delicacies. A top restaurant in New York used to keep a soup stock of animal brains to enhance the exclusive taste of their pricey soup. The direct transmission of a natural classical scrapie isolate to macaque monkeys (a relevant model for human brain diseases) has been recently reported to cause dementia after a 10-year silent incubation period with features similar to human cases of sporadic Creutzfeld-Jacob disease (s-CJD) – a rapidly evolving dementia with myoclonus, extra-pyramidal and cerebellar symptoms occurring annually in 1:1,000,000 population.
Tragically, variant CJD (likely BSE prions) was transmitted to humans through the use of pooled, infected growth hormone extracts from cadaver pituitary glands in the 1990s – cases are still being diagnosed. Neither Scrapie nor BSE has never been formally shown to be orally transmissible to humans – though any epidemiological studies are difficult with such long incubation periods and spotty recall of diets 10-20 years in the past. Recently reported in the UK are four cases of variant-CJD (thought caused by BSE prions) linked to past blood transfusions – a reason CJD is now screened for in the blood supply.
Several hypotheses are driving research into AD. Currently a dominant theory (according to The Economist, February 16, 2019, that dilettante journal of medical breakthroughs) is the prionic theory of Stanley Prusiner, who has argued that most neuro-degenerative diseases are prionic in origin. An emerging hypothesis is the relationship between neuronal hyperactivity and AD, observable in early stages of AD – normal activity being important for the formation of new memories and the retrieval of old ones. Clinical trials of levitiracetam (Keppra), an anti-epileptic, are ongoing.
The evil irony of this awful disease is not lost on physicians: the more our research has improved outcomes in cancer, heart disease and infectious diseases, the longer people live and become susceptible to brain disease. The Alzheimer Society of Canada reckons that currently in Canada some 500,000 souls (two-thirds of them women) are living with AD (with 10% institutionalized.) Each year, some 25,000 new cases are diagnosed. In 20 years, we may have nearly a million sad souls living with AD with all the silent suffering and sorrow – and the family and societal disruption that goes with them.
Seniors’ psychiatric teams are struggling. More support, including payment for caregivers, is required. This wicked disease is an international calamity needing a huge effort from the public and especially researchers. Causes and practical treatments must be found. Just as important, though achingly difficult, we must find a way to carry through the personal directives of patients (while they are able to give consent) to end their suffering – including medical assistance in dying (MAID). Would you want to end your life in a dementia ward? Not me.
Thank you to Drs. Wayne Chen and Alexandra Hanson, University of Calgary, for expert help.
References available upon request.