“… Now his wars on God begin;
At stroke of midnight, God shall win.”
— from The Four Ages of Man, W. B. Yeats
It’s hard, even for those who believe in afterlives, to contemplate that individual organisms become biologically irrelevant in this life once they’ve succeeded in shepherding the next generation to autonomy. It insults our deep sense of teleology, of being here for a purpose beyond just reproduction and ecosystem balancing interactions.
Luckily, humans undergo a very long period of neoteny: they need to acquire the specialized physical and mental skills required for dealing with technology and social groups, including language. So in humans (and a few other species that include orcas and elephants) experienced elders remain relevant – indeed, crucial – for a long time past peak reproduction. Even so, the average human lifespan hovered around the mid-thirties (with exceptions so rare that they were noted in myths and chronicles) until clean water and antibiotics extended it to almost three times its unaided length.
But this longevity came with a price attached. Our scaffolding was not made to last that long, no matter how precious its cargo. So anyone who goes past thirty will get acquainted with at least one of the degenerative age-linked diseases; primarily cancer and dementia. It’s also true that such diseases can strike young(er) people, but that happens to those who carry gene alleles (variants) that make them susceptible to the respective dysfunctions.
Cancer and dementia are broad umbrella terms for aggregate final-outcome phenomenology. Cancer means that specialized organ-specific cells that should have stopped dividing resume the process, spawning a mound of descendants (“tumor”) that often are semi-immortal. In contrast, normal cells die and are replaced in a set timetable for each organ, except for neurons, glia, ova and testicular Sertoli cells (it’s not just eggs that get old: sperm quality also declines with age because Sertoli cells are its maintenance crew). Incorrect resumption of propagation is usually the result of mutations, genetic or sporadic (for example, induced by radiation) that jangle the carefully calibrated choreography of the activators and inhibitors that regulate gene expression. When the inappropriately dividing cells become so de-differentiated that they no longer adhere to their relatives (aka contact inhibition), they detach and start creating colonies elsewhere in the body (metastasis). There are environmental and hormonal triggers for each organ (asbestos and cigarette tar for lungs, UV light for skin, lactation status for breast) but age is the cross-sectional risk factor.
If cancer is too many cells, dementia is too few. Many people use dementia and Alzheimer’s Disease (AD) as synonyms but, in reality, dementia is a much larger and more heterogeneous category – so much so that non-AD dementias often get misdiagnosed. This conflation is plainly visible in the statements that attribute the recent, too-early death of SF author Terry Pratchett to early-onset AD; in fact, Sir Terry suffered from Posterior Cortical Atrophy, a rare non-AD type of dementia that starts out by affecting visual perception.
Who we are as persons largely resides in our brains and the human brain is amazingly plastic. That attribute is what allows us to acquire unique skills as a species and new skills as individuals. Our brain will also reroute and rewire at moments of crisis (this capacity, incidentally, is the likely root cause of fibromyalgia), though it loses plasticity with age and adult neurogenesis is negligible, limiting regeneration abilities. If, for whatever reason – from a mutation to lack of oxygen to a blow on the head – an extended portion of brain tissue dies past the brain’s capacity to effect repairs, the eventual outcome is dementia: literally, loss of mind. If the hippocampus is affected, the result is inability to form and retain memories. If the substantia nigra, Parkinson’s Disease. If the blood vessels, impaired judgment and organizational skills. If the frontal lobe, disinhibition (inappropriate behavior), aphasia (problems with speaking) and extreme mood swings. Overall, dementia means that the invisible, seamless mental coordination upon which we utterly rely stutters: brain compartments are reduced to the mere sum of their parts and eventually even localized functions fail.
A few non-brain complications can also affect cognitive function – vitamin B12 deficiency, hypothyroidism – but these are reversible. On the other hand, brain-based dementia, once it starts, is progressive and irreversible. And although we know and continue to learn a lot about the neurodegeneration process at several scales, we have made zero headway in preventing, arresting or reversing it. We don’t even know what to look for as an early warning sign; not that it would avail us much if we did. Whereas cancer treatment has made enormous strides in terms of both effectiveness and fine-tuning, whatever medications are given to dementia sufferers are really attempts to ameliorate side symptoms – the horrific anxiety of early stages, the crippling discombobulation of later ones. In fact, currently most dementia sufferers will remain lucid and functional the longest if they’re given nothing at all.
Countless theories have been proposed about how dementia starts and spreads; although several are not mutually exclusive, many events/structures that initially seemed obvious pathogenic culprits (and hence potentially fruitful targets for therapy) have now been proved to be effects rather than causes. The most prominent casualty is the amyloid hypothesis, which posits that amyloid plaques act as poison or as dominoes that nudge neighboring neurons into the downward spiral. However, it turns out that amyloid plaques are in fact neutral depositories; the truly toxic entities are soluble oligomers – and vaccines that dissolved plaques would accelerate the progression of the disease. Furthermore, several types of dementia have no plaques (the tangle-only dementias, in which fibrillar deposits of the scaffolding protein tau are the diagnostic and causative entities). This does not mean that amyloid is not involved, since several types of early-onset AD are caused by mutations in enzymes that process the amyloid precursor. What it means is that there are many tributaries that funnel into the dementia main pipe, and a change in any of them may suffice to tilt the system into initiating the degeneration loop.
People fear suffering; but even more they fear loss of self. Dementia is the ultimate specter and its shadow is lengthening in step with our lifespan. So are its burdens on individuals and groups: half of the population older than 85 develops the disease. Also, younger people who would once have died from brain injuries sustained in explosions now survive them, only to become strangers to themselves and those who love them.
We will all face the journey into the dark. But the same sense of wonder and purpose that has made us explore beyond what we can instantly grasp – from galaxies to brains to quarks – also makes us want to meet the unknown (or the end) as ourselves.
Image: Pier and Sea, by A68Stock