WHY Is My Brain Slowing Losing It? Root causes of physical and functional changes in aging
Scientists have noted differences in the numbers of sensory receptors in human skin as a function of age in studies that date back to more than a hundred years. On the average, numbers of receptors/cm2 drop to 10-50% of youthful levels by your 70th birthday, with accompanying changes in sensitivity and discriminative abilities. For example, see Tornbury JM & Mistretta CM (1981) Tactile sensitivity as a function of age. J Gerontol 36:34; Gescheider GA et al (1994) The effects of aging on information-processing channels in the sense of touch. Somatosen. Mot Res 11:345.Your sense of temperature on the skin is affected for some — but not other — skin surfaces (Kenshalo DR (1986) Somesthetic sensitivity in young and elderly humans. J Gerontol 41:732.One of my former fellows (Dan Goldreich) has shown that that sensitivity and discriminative ability on the skin is a simple function of skin receptor density (see Peters RM et al., 2009, Diminutive digits discern delicate details: fingertip size and the sex difference in tactile spatial acuity. J Neurosci 29:15756) — which explains why females of any age — which have (on the average) just as many tactile receptors in their hands as do males — have significantly more sensitive hands, and generally finer hand control.Very interestingly, some older individuals do NOT lose skin receptors or manual sensation or control abilities. My hypothesis as to why: When you heavily engage your hand (or mouth or other) skin surfaces in discriminative behaviors (e.g., as a professional artist or dentist or other hand- or mouth or other-control expert), you heavily engage the autonomic nervous system as it makes continuous adjustments in blood flow and other homeostatic processes that, collectively, sustain skin sense integrity. This is an easily-testable hypothesis, but I have not yet found a scientist who has time to answer this simple — but really, from the perspective of aging populations, pretty important — question!
It might be noted that changes in our sensory abilities are also contributed to by changes in the mechanics of the skin (its gets thinner, loses elasticity, loses sweat glands and sensory hairs, loses underlying fat padding, undergoes vascular degradation, etc.), and to the physical receptors themselves. Stretch-sensitive receptors detecting skin pressure are affected by skin elasticity changes. They contribute very importantly to your sense of body position. The beautifully lamellated “Meissner’s corpuscles”, hair follicle endings, and “Pacinian corpuscles” that account for the exquisite interpretation of transient information from the surfaces of our hands and bodies slowly lose their morphological integrity as we grow older. See, for example, Schimrigk K, Ruttinger H (1980) The touch corpuscles of the plantar surface of the big toe. Histological and histometrical investigations with respect to age. Eur Neurol 19:49; Bruce MF (1980) The relation of tactile thresholds to histology in the fingers of elderly people. J Neurol Neurosurg Psychiat 43:730.
We also lose some sensitivity to superficial pain contributed differential by the reduction of a particular class of nociceptors (the myelinated A-delta pain afferents) that account for sharp pain sensations (e.g., see Tucker MA et al (1989) Age-associated change in pain threshold measured by transcutaneous neuronal electrical stimulation. Age Ageing 18:241. The sources of duller/aching pains have been argued to be less affected (also see Kenshalo, 1986, ibid.). Importantly, other body tissues are deteriorating, and those changes give rise to that continuously growing incidence of debilitating pain in the elderly (Thomas E et al. (2004) The prevalence of pain and pain interference in a general population of older adults: cross-sectional findings from the North Staffordshire OSTEOARTHRITIS project (NorStOP). Pain 110:361; also see statistics for arthritis vs age from the CDC: http://www.cdc.gov/arthritis/data_statistics/arthritis_related_stats.htm — or for lower back pain, from the WHO: http://www.who.int/medicines/areas/priority_medicines/Ch6_24LBP.pdf A dozen or two other pain labels pain(t) the same picture, i.e., further support the conclusion that we older folk almost all affirm: Older bodies deteriorate in ways that generate largely dull/aching/burning pains that debilitate us, with increasing growing probability, as we age.
Vision, hearing and balance impairments are also a growing problem in aging. For a conservative estimate of the numbers of individuals that have problems that require medical treatment for impairment of these great senses, see, for example: Dillon CF et al (2010) Vision, hearing, balance and sensory impairment in Americans aged 70 years and over: United States, 1999-2006. NCHS Data Brief, #31. www.cdc.gov/nchs/data/databriefs/db31.pdfNote that problems with dizziness and balance are the most prevalent cause of real problems, and because they increase risks of falls and limit mobility, are of high importance re our general well-being at older ages. See, for example: Baloh RW (1992) Dizziness in older people. J Am Geriatr Soc 40:713; Dominguez RO, Bronstein AM (1000) Assessment of unexplained falls and gait unsteadiness: the impact of age. Otolaryngol Clin
North Am 33:637; Marchetti GF, Whitney SL (2005) Older adults and balance dysfunction. Neurol Clin 23:785.
Visual problems attributable to deterioration of the eyeball (lens, cornea, retina) impact about 15% or older individuals (impaired to a medical level); in the great majority, eyeball and retinal physiology are relatively intact — albeit in a growing number of individuals, after corrective lens or corneal replacement or other ocular surgery. This is not the case in hearing, where most older individuals have some level of loss. A former research fellow from my laboratory who has conducted large epidemiological studies in elderly populations struggled mightily trying to establish a ‘controlled population’ of non-hearing-impaired seniors. You generally have to screen HUNDREDS of older individuals to identify a handful of >65 year old subjects with normal hearing extending up to 6 or 7 kHz without detectable loss, i.e., all across the speech frequency range. If you’re older, there is just a very high likelihood that your fragile inner ear has already suffered losses from sound exposure, from other vicissitudes in life, or from just being on the planet for so many years!
Changes in taste and smell with age have been well documented. Sensory cells in the olfactory epithelium AND taste buds are slowly dying off (and changing their morphologies for the worse) as the years pass by. Still, most individuals retain acceptable capabilities until very late in life. Olfaction has been argued to be the more sensitive to loss. Significant olfactory loss has been argued to presage Alzheimer’s and/or Parkinson’s Diseases (e.g., see Doty RL (1989) Influence of age and age-related diseases on olfactory function. Ann NY Acad Sci 561:76; Schiffman SS (1997) Taste and smell loss in normal aging and disease. JAMA 278:1357; and just for fun, Stamps JJ (2013) A brief olfactory test for Alzheimer’s disease. J Neurol Sci 333:19 — which points out that if you lose your ability to smell peanut butter under the right conditions, you had better make a doctor’s appointment)!
One multisensory ability that draws on ALL of the senses (and on complicated brain mechanisms that interpret their spatial relationships) that is inexorably degraded in aging is navigation. We’ll later argue that it is an especially important target of your regular brain-training exercises. For example, see Moffat SD (2009) Aging and spatial navigation: What do we know and where do we know it? Neuropsychol Rev 19:478.
As we’ve noted in the notes following earlier chapters, the brain (and spinal cord) slowly shrinks in volume as a function of age. See earlier references and Prestia A et al (2013) The in vivo topography of cortical changes in healthy aging and prodromal Alzheimer’s disease. Suppl Clin Neurophysiol 62:67 as one of many entries into this literature. Very interestingly, the shrinking of the human brain does not appear to be as prominent in our nearest primate cousins. See Sherwood CC et al (2011) Aging of the cerebral cortex differs between humans and chimpanzees. PNAS 108:13029.
Historically, age-related changes in brain volumes were long thought to arise largely through neuron loss. This misconception arose in part because there IS obvious cell loss in some highly visible cell populations (e.g., the neuronally atypical “granule cells” of the hippocampus and cerebellum). However, other very large neuronal populations (like the pyramidal cells of the cerebral cortex) appear to be constructed for the long haul in life; very few are lost across our lifetimes (see, for example, Freeman SH et al (2008) Preservation of neuronal number despite age-related cortical brain atrophy in elderly subjects without Alzheimer disease. J Neuropathol Exp Neurol 67:1205; Fabricius K ett al (2013) Effect of age on neocortical brain cells in 90+year old human females — a cell counting study. Neurobiol Aging 34:91; or Giannaris EL, Rosene DL (2012) A stereological study of the numbers of neurons and glia in the primary visual cortex across the lifespan of male and female rhesus monkeys. J Comp Neurol 520:3492. One very important new finding in these studies: While overall neuron loss is not great, there is a highly significant loss of glial cells — which contribute significantly to neuron action and plasticity.
I pointed out that there are numerous studies, again dating back for more than a hundred years, documenting the reduction in axonal arbor and dendritic elaboration vs age — and in myelination of local and long-range fiber tracts vs age — that, with changes in glial cell numbers, largely account for “the incredibly shrinking brain” of the average older individual. However, just as importantly: a) There IS some cell loss in aging that DOES impact brain operations. For example, there IS that progressive loss of granule cells especially prominent in the brains of inactive individuals, described earlier; or the loss of spiny inhibitory neurons in the basal ganglia that contribute to ultimately-catastrophic degraded motoric and cognitive function; or the loss of dopaminergic, serotonergic, adrenergic and cholinergic neurons in the subcortical ‘modulatory control machinery of the brain, all documented earlier. THESE ARE KEY PLAYERS, as repeatedly pointed out, in brain plasticity contributing to sustained brain health — and it is a very good idea to keep these brain cells alive and in good stead! b) Moreover, many neurons change their functional properties in ways that effectively impair them, re normal ‘adult cortical function’, i.e., they survive, but are less functional. For example: there is a selective degradation of somatostatin-immunoreactive and parvalbumin-immunoreactive inhibitory interneurons that critically underlie plasticity and activity-coordination processes. Because these neurons lose their immunoreactivity in aging, they have been imagined to have died off (see, for example, Stanley EM et al (2012) Interneuron loss reduces dendritic inhibition and GABA release in hippocampus of aged rats. Neurobiol Aging 33:431; doi:10.1016/j.neurobiolaging.2010.12.014; if fact, they’re generally still intact (but because they’re lost their immunoreactivity, and no longer ‘visible’ to the histological stains that reveal them). We’ve conducted a long series of studies that show that they aren’t dead and gone; they’re just immunoreactive ‘ghosts’ — who can be restored to normal functionality by intensive re-engagement.These inhibitory interneurons are also key contributors to brain plasticity processes.
There is no point of attempting to direct you to the hundreds of thousands of studies documenting changes in the physical body as we age. What is of greatest interest to us are changes in corporeal processes that are controlled by our neurology. Because physical corporeal and neurological changes track one another, we have to break down the notion that we have a separate set of “brain health” and “health” issues. A healthy body is dependent upon a healthy brain. And we have to sustain our body core (our basic pulmonary and cardio function) to sustain a healthy brain. This is especially challenging (but we CAN do A LOT to keep the core in good stead) when misfortunes and life and age substantially immobilize us.
When we first began training animals while documenting changes in the brain that accounted for neurobehavioral improvements in ability, we documenting a great principle initially stated in clear terms by the father of physiological psychology, William James (ibid.): Our brain changes in ways that account for the acquisition of ability on the path to mastery. Once mastered, that skill is supported by out “non-declarative memory”, i.e., can be performed (“remembered”) automatically, with minimum attention to the task. See Merzenich MM et al (1990) Adaptive mechanisms in cortical networks underlying cortical contributions to learning and nondeclarative memory. Cold Spring Harb Symp Quant Biol 55:873. A common conclusion based on many studies is that the “non-declarative memory” supporting these “automatic’ behaviors is crucially supported by the sub-cortical basal ganglia. To the contrary, I believe that heavy doses of stereotypy degrade the basal ganglia, and am conducting studies trying to determine the extents to which that is true — as they bear important implications for PD genesis.
As repeatedly noted above, most older brains suffer significant neuronal losses in the subcortical ‘limbic system’ machinery modulating learning and memory processes, regulating sleep, and controlling mood. Changes in these areas are commonly identified as the FIRST changes occurring on the path to Alzheimer’s, Parkinson’s, Huntington’s — and a dozen other ‘diseases’. Cells expressing monamines (dopamine; noradrenaline) are especially susceptible to loss; but the time of onset of Parkinsonism, you’ve lost about 2/3rds of these neurons in both the locus coeruleus (noradrenaline) and ventral tegmental area/substantia nigra (dopamine). For example, see Zarow C (2003) Arch Neurol 60:337. Cells releasing acetylcholine and serotonin don’t die off to the same extent, but they become metabolically less active, and ultimately produce relatively limited neurotransmitter (or the ‘transporters’ that deliver these neurotransmitters out to the wider brain; see, for example, Mufson EJ (2000) Loss of nucleus basalis neurons containing trkA immunoreativity in individuals with mild cognitive impairment and early Alzheimer’s disease. J Comp Neurol 427:19.). At the time of diagnosis of a ‘mild cognitive impairment’ foretelling AD, for example, nearly all of the acetylcholine producing cells are still intact — but are functional ghosts of their former selves. So, too, are most of the neurons that sourced the neurotransmitter serotonin to the wider brain.
Older brains operate more often at a level of abstraction… The most compelling studies supporting this argument have come from experiments in which aural speech was manipulated in ways that reveal our powerful bases of signal abstraction at an older age. Initial studies showing that detail-less acoustic forms of speech (e.g., band-passed modulated noises closely tracking the speech envelope) were understandable were conducted by a former fellow from my laboratory, Robert Shannon (see Shannon RV, et al (1995) Speech recognition with primarily temporal cues. Science 270:303.). Interesting follow-on experiments have shown that speech in this form only very weakly engaged memory processes. The Cambridge University professor Brain Moore and colleagues have contrasted the intelligibility of this highly processed speech with another radically different form, in which almost all speech envelope information is removed, while conserving all of the spectrally specific moments of change in signal variance in the speech input stream. That was accomplished by high-pass filtering of the output of 16 vocoder channels spanning the speech frequency range. There is very little in common, re signal structure, for THIS form of speech and the modulated-noise-while conserving-envelope form studied by Shannon. Both are intelligible (see Moore BC, 2008, Basic auditory processes involved in the analysis of speech sounds. R Soc Lond B 363:47; Moore BC, 2008, The role of temporal fine structure processing in pitch perception, masking and speech reception for normal-hearing and hearing-impaired people. J Assoc Res Otolaryngol 9:399). Importantly, in contrast with the modulated-noise processed speech, that high-passed filtered channelized (neurological detail-rich) speech strongly engaged the memory machinery of the brain.In another class of studies, scientists have integrated all information together in temporal chunks of different duration, or have flipped the spectro-intensive-temporal details in chunks of different duration, showing that recognition of speech robustly compensates for remarkable reductions of acoustic input details — i.e., that your powers of abstraction conserve speech reception abilities in the face or powerful reductions of incoming speech-detail information.We have created and experimented with these (and other) forms of processed speech, and have shown (in unpublished studies) that children (especially young kids) have much weaker powers of abstraction than to older adults. Our surmise: Your correlation-based processes underlying speech reception are powerfully engaged, via ultimately billions of moments of engagement, to ‘fill in the details’ re speech reception accuracy. Over time, you can effectively remove them, without detecting their loss.Until, that is, you try to remember what was just said.
