| Summary - According to an uncritically accepted axiom, the human brain's capacity for longer-term memory storage is never overloaded. This viewpoint is shown to be contrary to all evidence and beyond reasonable credibility. The entire currently-obtainable evidence for or against overload comes via the presence or absence of its manifestation in behaviour. This manifestation would be as an incurable, deteriorating, specific form of memory disorder, associated with old age and consequent to increased data-inputting and reductions of brain capacity. There is in fact such a disorder, namely Alzheimer's disease and other dementia. This relationship provides elegant explanations for various peculiar findings, without encountering any counterevidence. The premorbid accumulation of tangles in the hippocampus is explained via an integration of existing hippocampus theories. Long-term low doses of drugs that reduce memory formation could prevent or delay dementia. TV-watching, videos, and some memory-enhancing nootropic drugs could increase risk. © Harcourt Publishers Ltd |
|
DONT READ THE FOLLOWING - INSTEAD DOWNLOAD THE ENHANCED UPDATE DRAFT BY RIGHT CLICKING THE adtheo.pdf LINK (above) AND SELECTING "SAVE AS" (other procedures apply for non-PC/Internet Explorer users)
The unthinking of axioms has played an important part in scientific progress. Examples include such notions as the earth being the centre of the universe, of humans originating independently from animals, and the existence of absolute velocity. An outstandingly strongly-respected axiom of psychology is that the human brain has such a surplus of long-term memory capacity that it never ever becomes overloaded. The resolute adherence to this axiom without reference to any supporting evidence appears to find some explanation with reference to the Copernican and Darwinian revolutions. In all three cases the self-concept of us humans is under attack: are we not the centre of the universe?; are we not an altogether different class from mere animals?; and can we not go on learning and maturing forever once we have discovered the secret of immortality? Questioning of this axiom inevitably brings us into consideration of one of the most important medical problems of our time (in developed countries at least), namely dementia (1), which is expected to become yet more common as more people live longer. Dementia is a syndrome characterised by deterioration of memory followed by general deterioration of learning, thinking, judgement, and other brain-dependent functions. Various causes have been identified, but the majority of cases involve either failures of the blood supply (vascular dementia) or a largely mysterious insidious degeneration of the brain, generally called Alzheimer's disease (AD) for want of a better name. Numerous ideas have been advanced about the causation of AD, but all are very limited as explanations of the phenomenon. They have had little or nothing to say about such important matters as: 1. The specific symptoms and why they take so long to develop. 2. The epidemiology and risk factors. 3. The evolutionary context. 4. Why there are problems with genes and molecular events such as beta-amyloid accumulation anyway. 5. Why the pathology is concentrated on particular areas of the brain. 6. Why it is that very different causes produce much the same syndrome of dementia. Instead, those ideas are almost entirely confined to the molecular level. But understanding of the molecular processes remains extremely sketchy and speculative (2,3). Empirical investigations face great difficulties, given a slowly-developing disorder of a complex organ hidden in the skull, with memory a far from straightforward phenomenon anyway. The molecular biology of the brain is dauntingly complex. About 10,000 genes are expressed in each neuron, but the function is not known even of those genes and proteins directly linked to AD, such as amyloid precursor protein and the presenilins. And one molecular researcher has said of the preoccupation with those proteins, that it is very much like a drunk searching for his keys under a lamp because that is where the light is. Given such a level of uncertainty surrounding the molecular ideas and findings, they will be referred to herein only to the limited extent that they appear to be relevant. If progress is to be sustained it is essential that the molecular-level concepts be put into a context of a wider understanding of AD. Thus it is evident that there is a need for further sound ideas about the causation of dementia. This paper considers the questions of: (i) whether overload of longer-term data-storage never occurs; (ii) whether such overload would manifest as dementia/AD or otherwise; (iii) to what extent dementia/AD can be explained in terms of such overload. And further questions emerge, such as whether known drugs that reduce memory formation could be used to prevent AD. Six referees of this paper (4), for Psychological Review and Psycoloquy, contended that the paper selectively picked out evidence supporting the author's conclusions, while ignoring damning counterevidence. These referees' rationales are in all significant respects unambiguously erroneous (4) (and I myself searched thousands of papers for counterevidence but found none). They further contended that there was insufficient support for the paper's conclusions, a phrase that has long-unimpressive echoes through the history of science. It is here suggested that there is insufficient evidence that these critics' claims are worthy of any credence, rather very much the contrary (4). Readers are recommended to refer to my rejoinders to these referees for clarifications here omitted for lack of space, but they should take note that the referees' reports are very extremely misleading. (A note first about the term "longer-term memory": There exists a well-established distinction (5,6) between short-term memory with a duration up to about 20-30 seconds, and long-term memory for anything over 20-30 seconds, including "recent memory". To minimise confusion, long-term memory is herein referred to as longer-term memory.) Does Overload Never Occur?Evidence of the existence or non-existence of overload could take two forms. If we could measure unused memory storage capacity or the accumulation of data in the brain then we could observe the presence or absence of overload relatively directly. But this is not possible at present. So the entire currently available evidence for or against overload must come via the presence or absence of its manifestation in behaviour.How then would overload of longer-term memory manifest in behaviour? It would inevitably involve some failure of longer-term memory, and clearly it would become more common with age and be unremitting. We do in fact see just such a failure of longer-term memory which becomes more common with age and is unremitting. In these respects dementia clearly looks suspiciously like a manifestation of overload. So at this stage of our study the case stands in favour of the notion that overload exists and manifests as dementia. Before getting into a more lengthy examination of to what extent findings concerning AD and other dementia accord with what would be expected of overload let us consider whether the existence of overload can be dismissed on grounds of logical absurdity or improbability. It should be made clear that the following paragraphs are not intended to "prove" or argue for the existence of overload, but merely to consider whether there is any inferential disproof of overload. The evidence (in outline) on the matter has already been presented above. If a person's old memories fade or are lost as fast as new ones are acquired then that person will not develop overload. Any such mechanism of ongoing fading or loss would greatly reduce any memories spanning a lifetime. But not only does this find no support in experimental studies, but is also decisively refuted by experience from old people many of whom have more numerous memories of eighty-ninety years previously than of more recent times. It would be perverse enough to suppose that overload is usually prevented by such a non-evident process, but the idea that it must always be thus prevented is surely well beyond reasonable credibility, given the diversity that exists in psychological phenomena. An alternative possibility is that overload would always be prevented by reason of substantial spare capacity. Again this is a very rash notion. Human memory is remarkable enough anyway on account of its great capacity, flexibility and speed of access, and capability of retaining data over many decades of life. It seems very far-fetched to suppose that the human brain, which consumes approximately one fourth of the body's energy intake, would be granted great unused spare capacity which would by definition constitute a considerable burden in natural selection. And certainly not always. The above reasonings are not invalidated by the encoding of memories being in distributed form (see below); the crunch still must come, when demand starts to outstrip supply (7). We may thus end this section by concluding that the traditional assumption that memory overload never occurs is not supported by the evidence but instead is intensely challenged by it, and furthermore is highly implausible on logical grounds, and that the relationship between dementia and overload is worthy of further consideration. Would Overload Resemble Dementia?It may be tempting to think that the primary (first-occurring) symptom of overload would obviously be lack of storage space to fit more data in, hence inability to form new memories, as usually seen in dementia. However, the reality is not so straightforward.There is much reason to believe that longer-term memories are stored by means of long-term changes of connectivity between neurons, that is, long-term potentiation (LTP) of synapses. But one synapse of LTP does not correspond to one item of data stored. Instead each item of data is diffused in a neural network as a pattern of LTP over numerous synapses, partly overlapping with the patterns recording other items of data. The networks are intricate three-dimensional tangles, but can effectively be conceptualised as quasi-two-dimensional matrixes of neurons (the "rows" correspond to inputs, and the "columns" to outputs) (7). Such matrixes have properties such as completion, graceful degradation, and rapid recall. When computer models of such matrixes become overloaded the result is not that further data cannot be recorded but rather that errors develop in pre-existing data (7). So it would seem to be expected that memory overload would manifest primarily as corruption of existing memories; which brings us into a clash with the facts of dementia, which generally starts with difficulty in forming new memories (8) (and incidentally not a fault of retrieval (9,10) or maintenance (11,12)). This is an unusually longstanding finding. Esquirol (13) observed in 1838 that "senile dementia results from the progress of age ... and commences with feebleness of memory, particularly recent memory". Prichard (14) stated in 1835 that the first stage is impairment of recent memory: "forgetfulness of recent impressions, while the memory retains a comparatively firm hold of ideas... from times long past". The diagnostic criteria of the American Psychiatric Association (15) specify impairment of "short-term memory" indicated by "inability to remember... after five minutes" (i.e., long-term memory in standard terminology). Note that the usual primary symptom of dementia is indeed a fault of memory. And further that the fault is not in transitory working memory, or immediate or short-term memory of a few seconds' duration, which is recognised as being independent of longer-term storage. And yet the usual primary symptom of dementia is difficulty in forming new memories, rather than the corruption of existing memories that overload would apparently produce. Or is the reality yet more complicated? A Third Stage of Understanding?Arguably the reality is yet more complicated. It should first be noted that the longer-term memory store is almost certainly not one large homogenous matrix, but rather numerous relatively separate ones (with specialisation for words, faces, etc.). Thus overload would be expected to occur in some over-used matrixes long before overall capacity would be exceeded. Furthermore, brains have a notable capability of adapting to damage or abnormality by transferring functions to other areas. And evidence of such a diversion of function has been observed in AD (16), with memories stored in atypical locations.These observations clearly imply the existence of some mechanisms for detecting that there is a lack of capacity in the areas diverted away from. Natural selection will favour further mechanisms, which enable local matrixes nearing overload, to signal their lack of spare capacity, thus activating diversion to other locations. These anti-overload mechanisms, as we could call them, will have the effect that local matrixes do not become corrupted by local overloading but instead become closed to or resistant to storage of new data. When eventually all the localities reach this state the effect is one of a whole memory store that has not become corrupted but instead develops the usual primary symptom of dementia--failure to accept new memories. (By this stage natural selection would have little new to contribute, given the exhaustion of capacity and the person being relatively old anyway. But is it possible that the resurgence of neuronal sprouting seen at the threshold of AD may be a last-ditch mechanism to generate new capacity.) Thus this third stage of understanding restores to us the same conclusion we abandoned from the simplistic first stage--that overload would indeed manifest primarily as failure to form new memories. So how could an anti-overload mechanism operate? A possibility is that synapses in a state of LTP thereafter transmit a molecular back-signal to inhibit input from the afferent neurons. Another possibility is that in sustained LTP a molecular messenger is produced which diffuses randomly from the neuron such that high levels of LTP in a matrix produce high local levels of the messenger, with excessive levels inhibiting further LTP. Alternatively rather than producing a new messenger, LTP may inhibit a pre-existing one such as one of the factors essential for neuron growth or survival. This last seems the most plausible. Various distinctions have been proposed between different forms or aspects of memory in humans. Among the best-established is that between consciously-known information (explicit/declarative memory) on the one hand, and unconscious skills (procedural) and other implicit memory on the other. There can be little doubt that in the information-overloaded developed world much demand is made on the capacity of explicit declarative memory. Conversely, relatively little demand is made on memory for skills, as life becomes more and more a matter of just pressing buttons to do tasks that had previously required learning of skills, such as washing, cooking, entertaining, and making things by hand. So overload would be likely to occur in the declarative field before the procedural field. Thus the usual primary symptom of dementia corresponds remarkably well with what we would expect from memory overload interacting with anti-overload mechanisms. There are many forms that the mental disorder most strongly linked to old age could conceivably take. It is surely remarkable that instead of all the other possibilities, we observe predominantly a defect of memory, of longer-term memory, in the declarative area, beginning with difficulty forming new memories in particular fields (e.g. names) (as local overload develops), and progressing to greater and more widespread failure to remember (as overload becomes general). Now let us suppose that as often happens with mechanisms, the anti-overload mechanisms sometimes fail. Matrix overload would then occur and prior memories become corrupted (7). Let us imagine ourselves in the position of a person in whom corruption of memories occurs (and of course without any knowledge of matrixes or overloading). Suppose that overnight our memory of a familiar person or thing has become corrupted. Our memory of the person or thing is now discrepant from the unchanged reality, but we would not perceive it thus, but rather as the person or thing having changed. We would have no idea the change was in our mind, and would try to devise some explanation for the mysterious occurrence. It so happens that demented persons do sometimes become convinced that familiar persons have been replaced by imposters, that their house has been replaced by a near-identical one, that other things have been replaced by inferior imitations, false beliefs which have been classed by psychiatrists as delusions (17,18). Indeed such delusions are the primary symptom in some cases. These very peculiar symptoms--which differ from the delusions of schizophrenia--are surely extremely powerful evidence for the view that overload occurs in dementia. The fact that such symptoms are not predominant merely indicates that the antioverload mechanisms usually do not fail. We will now consider another aspect of the dementia/overload comparison. Would not the onset of overload manifest as a sudden transition from normal functioning at one moment to total cessation of longer-term memorising at the next? A lifetime graph of dementia memory function would indeed show a precipitate decline from a perspective of decades, but clearly not from one moment to the next. There is good reason why such an instant transition would not be expected. The memory in the brain is not like a computer memory, in which all the memory locations are ordered in a continuous logical sequence through which a systematic search for free space can be conducted. Even computer hard disks become sluggish if free space is limited and scattered. Almost certainly the finding of room for new data in a nearly-full brain would present a problem akin to finding a needle in a haystack, and the problems of overload (and consequent degeneration) could start in some areas while space still remains elsewhere. Causes and Correlates of DementiaSome readers may be suspecting that the overload theory implies that a high level of education is a risk factor for dementia; which is apparently contradicted by the evidence that it is associated instead with low levels of education (19). But this question is complicated by the substantial correlations of education with IQ and social class. It has been shown that the association with education is due to the involvement of IQ (20). Schmand et al suggest that this is due to higher IQ conferring greater brain reserve capacity, a concept with obvious resonance here; but more straightforward is the view that the more intelligent persons store data more efficiently than those who have to learn things perhaps ten times before getting them correct (21,22).Furthermore, there is strong grounds for supposing that educational activity does not produce more data-inputting than other common activities. Indeed there is strong grounds to suppose that studying produces less data-inputting than TV-watching or socialising: a computer file of the text of this paper would be about 40Kb, whereas a typical TV program would be well over 100,000 times as much. For all these reasons, the findings on education do not challenge the overload theory but rather support it. Several conditions producing dementia involve decrease of functioning neural matter, caused by environmental factors. Dementia Pugilistica results from brain atrophy following blows to the head, Creutzfeldt-Jakob disease involves spongiform degeneration caused by prion infection, and vascular dementias involve brain damage after circulatory impairment. There can be little doubt that these would all involve reduction of capacity for memory storage. And the ApoE gene is thought to affect efficiency of neuronal repair, which would obviously affect capacity. Remarkably consistent with the overload theory is the finding that the data-inputting activities of reading, watching TV or movies, or listening to radios are significantly correlated with dementia 20 years later (23), against the researchers' expectation that such activities would be protective instead. A more recent attempt to find activities that protect from dementia (on the principle of use-it-or-lose-it) likewise found that TV-watching and reading did not help and that only gardening, travelling, and odd-jobs and knitting were protective (24). These activities are notable for being sufficiently boring to many people that they prefer to do something else at the same time. These findings have an obvious relationship to the dearth of evidence of dementia in less-developed countries, in striking contrast to its major significance in developed countries. A community survey of 9000 Nigerians including 932 elderly found no subject with dementia (25). Likewise an autopsy survey in Nigeria found absence of the plaques and tangles characteristic of AD. And yet Americans of black African lineage commonly have AD. Thus it seems highly likely that the absence of dementia in Nigeria (and probably other less-developed areas) is at least partly due to a much lower level of data input in localities where printed and broadcast words and images are much fewer. Furthermore, in the Canadian state of Manitoba, natives in remote reserves have been found to have much lower age-corrected prevalence of AD as compared to residents of the capital Winnipeg; and no higher levels of dementia in general even though they have much higher occurrences of risk factors (strokes and alcoholism) (26). Further support for the notion of limited capacity exists in the finding that sub-threshold levels of AD pathology and vascular pathology can combine to produce dementia (27,28). Alzheimer's DiseaseAD does not involve any known assault on the brain from external physical factors. Consequently the question arises of whether it is the manifestation of straightforward overload due to accumulation of data over many years. However, such a neat view may seem to be challenged by the genetic links, the degenerative pathology of plaques and tangles, and the finding that degeneration starts in the hippocampus, not thought to be the site of storage of memories. We will now consider to what extent these findings are compatible with the idea of AD as straightforward overload.The various reports of genes associated with AD have not demonstrated actual mutational events but merely genetic differences. Some of these could modify the response to overload, making it more or less damaging. This latter ties in with the evidence (bimodal distributions) of two subtypes of AD (29); the type with the more severe and rapid degeneration could well involve less benign anti-overload mechanisms. And the ApoE gene, if it affects efficiency of neuronal repair, obviously would affect the degenerative consequences of overload. Other AD-linked genes could confer increased premorbid memory encoding. There are considerable individual differences in rote memory ability, even when general intelligence in partialled out (30). There is evidence that memory traces can be multiplied in the brain and transferred to different areas (31). Enormous differences have been observed between species in the rate at which memories are consolidated into enduring form (32), and it would be odd if there were not also significant variance among humans. As regards the neuropathology, Alzheimer's disease is not such a straightforward concept as is sometimes assumed. Its "defining" features--senile plaques, neurofibrillary tangles and dementia--do not consistently go together (33). There are cases in which numerous plaques are seen with very few tangles, and vice versa. Other cases have large numbers of widely distributed plaques in the absence of dementia. And dementia can occur when only a few plaques or tangles are present. What does go together consistently is that large numbers of tangles in the cortex are found only in demented cases (34). And the tangles have been found to have the more consistent association with dementia (33). They also occur in Dementia Pugilistica (33). In line with these and other findings it is conceivable that the tangles are a consequence of memory overload. The plaques are neither necessary nor sufficient to produce dementia. The literature is thick with studies hinting that they are not crucial to the causation of AD. But the common practice whereby AD is defined in terms of presence of amyloid-containing plaques makes it inevitable that genes relating to amyloid would be linked to it. The plaques (or the associated beta-amyloid) may be a contributing cause of reduced capacity and hence overload. Or they could be a manifestation of anti-overload mechanisms. It has been found that persons who are free from dementia despite relatively large numbers of plaques tend to have larger brains with more larger neurons, suggesting more reserves of memory capacity (35). Two of the areas of greatest profusion of the tangles, the temporal and frontal lobes of the cortex (33), are thought to be sites of storage of declarative memories (36). But the tangles also occur in equal or greater profusion in the hippocampal system and amygdala, which appear to be involved in memory formation rather than storage. Indeed tangles accumulate first in these locations, and many older persons are thus affected without developing dementia (about 50% of apparently normal persons in the fifth decade are affected) (33). It would be unacceptable to fail to consider the questions these finding pose, of why the pathology first manifests in seemingly the wrong area and develops so long before morbidity manifests in behavior. We must therefore proceed at this point to some further consideration of the hippocampal system and how these findings may be related to memory overload. The hippocampal system has been the focus of a great amount of research, theorising and controversy, and is clearly a very complicated mechanism. However, despite their seeming contradictions it may be concluded that several theories are well on the way to the basis of a proper understanding (including refs 37-45). Several theories propose that the hippocampus contains a sort of data store (42-45); that of O'Keefe and Nadel proposes that it is a long-term store of place-representations, extended in humans to include semantic material. Some other theories consider that the system has a role for memory-processing involving a wider range of concepts ("cue-conjunctions") (37-39), or for indexing of the cortical longer-term store (45). The crucial idea that the prior theories have all but reached is that of the hippocampus as containing a store of all existing concepts and classifications, like the department of a library wherein the books are assigned their classification codes. This would enable it to serve various functions. Firstly it enables detection of new data that fails to fit into existing concepts/ classifications, thus detecting novelty as in Gray's behavioural inhibition system. Secondly it enables long-term memories to be effectively retrievable and distinguishable by reason of a classification system analogous to that of a library, and thus gives the effect of Eichenbaum's "relational processing"; and by amplifying the distinctiveness of dissimilar data it reduces inefficient redundancy in storage, as explained in Rolls's theory. It would take too much space here to give a full account of all the evidence relating to this conception (much of it is reviewed in the cited theories), but it may be noted that the hippocampus consists largely of a sequence of matrixes, with LTP capability of several weeks demonstrated, and also sustained habituation responses to familiar stimuli. Overall, this viewpoint of the hippocampal system arguably unites the various theories into a much more coherent and credible account than has hitherto existed. Relating the above to the memory overload concept, if the hippocampal classification store becomes overloaded long before the main memory store, then tangles will develop there first, as is observed. The effect of such overload would surely be that new memories fitting into pre-existing categories could still be formed, but new categories of memory could not. (This being less severe than dementia, there would be less natural selection for hippocampal capacity, hence overload would be expected to occur there first as suggested.) This overloading of hippocampal storage could be a reason why some older persons (though certainly not all) become incapable of accepting novel ideas, and indeed why novel scientific ideas are often only appreciated by younger scientists (46,47). It seems likely that succeeding stages of the hippocampal system would be characterised by increasing elaboration of the classification system, hence greater volume of data storage, so it may be significant that the pathology of AD starts at its output end and progresses retrogradely (48). The amygdala is thought to have a similar role to the hippocampus but more involved with emotions and motivations (49). Perhaps it gives classifications of memories according to emotions/motivations to supplement the experience-generated classifications employed in the hippocampus. A recent finding (50) of a so-called transcript mutation related to the amyloid found in the plaques could be a manifestation of long-term memory encoding. A well-known problem of very-long-term memory is how the encodings endure despite molecular turnover, and it has been argued that change at a primary transcription level of gene-expression must be involved. If so, the encodings could conceivably manifest as transcript mutations. Reversible Dementias and Drugs for ADThe preceding pages have pointed towards the view that dementias can be caused by overload following either (i) accumulation of data over time, (ii) reduction of capacity, or (iii) a combination of these. To these causes may be added a fourth: (iv) conditions that temporarily block or impair formation of LTP and hence temporarily reduce available capacity. This fourth possibility accounts for that minority of cases of dementia which are reversible.Recently some memory improvement has been achieved in AD by using cholinergic-boosting drugs. These drugs can retard the deterioration in about a third of cases by up to about 9 months. It appears that cholinergic neurons have a general activation effect on the memory formation processes. Their numbers and functioning are greatly reduced in AD but this is generally considered to be a secondary consequence of pathology of the neurons they control. From the point of view of the overload theory the partial and temporary improvements could be because the drugs somehow increase the 'pressure' for encoding in marginally overloaded capacity, perhaps overcoming an anti-overload inhibiting factor. It is also conceivable that their benefit is really via an unintended mechanism, such as reducing inflammation or otherwise restoring lost capacity. Either way it would be expected that in due course the extra capacity would be used up and deterioration resume, as is found. The overload theory also explains the difficulties with producing animal models of AD. The cholinergic therapy that has been largely disappointing with humans is much more successful (51) in treating the effects of the decline of cholinergic function that occurs in rats, accompanied by parallel decline of spatial memory (52). Also the tangles characteristic of AD are never observed in non-humans, with the exception of one elderly primate (53). The theory obviously predicts that an effective animal model of AD could only be produced by replacing the extremely unstimulating life usual for most laboratory animals with much more data-rich circumstances. Going Beyond the Scope of this PaperThe overload theory arrived at here does not as yet constitute a fully worked-out theory of everything about AD or any other sort of dementia (though it clearly encompasses a wider range of relevant considerations than any other).Little has been said here about the progression beyond the onset of memory loss and memory corruption. The notion that overload could lead to degeneration is not far-fetched: there are various ways in which it could occur, such as the following. (i) Along with the generation of LTP (or whatever constitutes the durable record) there could be generated messenger molecules tending to inhibit further LTP generation in that area (thus acting as an overload inhibitor). Up to a certain concentration this messenger has no harmful effects, but as LTP continues to rise in a local network, the concentration of the messenger surpasses a threshold beyond which it becomes neurotoxic. (ii) A variant of the above is that instead of producing a messenger, LTP decreases production of some trophic substance and in due course the level becomes insufficient to prevent cell deaths. (iii) Conceivably a bit of data in search of a storage location involves or has the form of a free radical, neutralised on finding a storage space. A mere delay in finding the space would leave this harmful radical doing damage, but when there becomes an accumulation of the unassigned radicals degeneration would certainly take off. Notably, increased free radicals have been reported to be a significant contributor to AD degeneration (54). Elaboration of exactly how the degeneration leads to the progressive decline to global dementia would be unnecessary speculation at present. It suffices to say that it is not surprising that the degeneration of cortical neurons leads to degeneration of the functions associated with them. Little has been said here more generally in respect of precise details of molecular causality. Again, this would be too speculative at present; no one else is presenting an integrated account of all these matters either, so its absence here hardly constitutes a notable fault. And it should be made clear that the fact that a theory has not been elaborated to account for certain findings does not constitute a damning failure such as manifest incompatibility would do. For example, Leslie's widely discussed (55) theory-of-mind theory of autism addresses only a few of the findings explained by Clarke's (56) autism theory, but it does not follow that the theory-of-mind theory cannot be a valid partial explanation of a few aspects of autistic behavior, even though it fails as a general account. Also there is no consideration here of the early symptoms of some less typical conditions commonly labelled as dementias. Even if these conditions have some fundamental commonality with AD and the like, there is an important conceptual confusion to beware of. Consider, for example, autism in which encephalitis can be a factor. There is no non-arbitrary way of dividing up the encephalitis-autism combination into the encephalitis bit and the autism bit. But it would be of little value to insist that the fever and headache be considered primary symptoms of autism is these cases. Of course any severely degenerating disease of the brain would be liable to eventually reduce storage capacity and thus lead to memory overload. Other important fields of inquiry into dementia, such as the preservation of functioning implicit memory, have not been covered here, for the simple reason that they do not impinge significantly on the questions that the paper is concerned with addressing. ConclusionsThe traditional assumption that longer-term memory never becomes overloaded has been shown to be highly implausible. The entire evidence available at present comes via the existence or non-existence of the manifestation of overload in behaviour, which would necessarily take the form of a progressive, unremitting condition starting with difficulty forming new memories, of the declarative and longer-term sort, increasing in prevalence with age, and having as risk factors reduced brain capacity and increased data input. We do in fact find exactly such a condition and it is that which is called dementia. The probability that this degree of concurrence would occur by chance must be very low. We can therefore dismiss as incredible and effectively disproven both the assumption that overload never occurs and the assumption that it does not manifest as dementia and Alzheimer's disease.It follows that we are logically obliged to have very high confidence in the antithesis of these assumptions, namely the theory that memory overload is the principal cause of AD and is the common factor underlying the syndrome of dementia. Thus the question that arises is not "how credible is the theory?". Rather, how many shreds of credibility has the counter-theory, that overload never occurs or does not manifest as dementia, and that dementia exists because of some other, unknown, reason (and such findings as concerning television or Nigeria or delusions of substituted houses or persons have some other explanations)? Those who wish to adopt the standard hostility to innovative ideas should attempt to compose a paper to justify their counter-theory that overload never occurs or else does not manifest as dementia. Just as not one criticism has been published of my three previously published theories, we can be confident that no such alternative paper is going to appear in print. The principal and other suggested links of the theory are shown in figure 1. [Which can be seen in adtheo.pdf or adtheo.rtf] A feedback link from degeneration to capacity reduction is omitted for clarity but may play an important part. Hypothetical elements are notably outnumbered by empirical elements, which is characteristic of a theory having low speculativeness. The theory presented here has in common with the theories of autism (56), manic-depressive illness (57) and societal breakdown (58) the concept of problems being caused by "too much of a good thing". This looks likely to be a useful concept to consider in relation to many other medical or biological problems. The theory makes various predictions. For example, long-term low doses of known drugs that reduce memory formation would be expected to prevent or delay the course of dementia. The use of memory-enhancing drugs by students could well become a risk factor for AD (depending on how they work). No cure should be possible that does not wipe out pre-existing memories or somehow provide extra capacity. Currently various projects are afoot for devising of drugs to intervene in what they hope is the basic causality of AD pathology. These are all very speculative at present. The molecular understanding is not yet developed sufficiently to permit any predictions of the merits of these projects, but interpretations of molecular findings in the light of this paper may make this possible eventually. Also predicted is a build-up of LTP (and or other representations of data) in the brain over successive decades, which could be used as a predictor of AD if means of measuring it can be found. The theory also predicts that Alzheimer's disease will increase more than expected from ageing of the population, due to increase of information exposure, and that this will be particularly marked in developing countries experiencing a substantial increase of video and broadcast information. The excessive growth of mobility may also be an aggravating factor (58). Interesting questions are posed, such as whether excessive watching of TV and videos should be avoided, and whether some persons may be protected from dementia by a tendency to permanently encode relatively little of the data they encounter. It is conceivable that future researchers could make measurements showing that demented people do not have significantly reduced spare memory capacity. It is further conceivable that they could find that (i) longer-term memory formation is not impaired in dementia, (ii) substitution delusions cease to occur as from 1999, (iii) dementia is associated with youth and high IQ, with avoiding of TV and videos, and with technological underdevelopment, while (iv) AD pathology begins in a different area than currently supposed, (v) animal models of AD are readily produced by using sensory deprivation, and so on. All this falsification is in principle conceivable, but it is extremely improbable even in part. That extreme improbability is the indicator of the very high quality of this theory, notwithstanding the contentions of those whose professional motivations favour uncritical faith in the conventional wisdom. The questions posed in the title of this paper can be answered decisively. The evidence that overload does occur and manifests as Alzheimer's disease and other dementia, is overwhelming. |