LE JOURNAL CANADIEN DES SCIENCES NEUROLOGIQUES

Functional Implications of Changes in the Senescent Brain: A Review

CHARLES H.M.BECK

SUMMARY: The morphological, chem­ and altered affect. Cholinergic hippo- change, a reduction in ambition and ical, and physiological changes in I he brain campal and neocortical systems were activity, an increased difficulty in accompanying old age are reviewed. The chemically and physiologically abnormal comprehension and an increase in time deterioration of the striatal and hypo­ in the aged. The implications for slowed and effort necessary for performance thalamic dopaminergic systems were im­ cognitive processing and persistance of the of familiar duties. Presenile dementia plicated in the onset of age related memory trace are presented. is viewed as an acceleration of this Parkinsonian-like slowing of performance process of mental deterioration (Kolb, 1968). RESUME: L'auteur passe en revue les emotions modifiee. Les systemes choliner- The first section of this paper changements morphologiques, physiolo- giques de I'hippocampe et du neocortex describes the physically visable, i.e., manifestent aussi chez les vieillards des giques, el chimiques qui accompagnent la morphological changes, that can be vieiles.se. La deterioration des systemes anormalites physiologiques et chimiques. seen in aging brain. Although the dopaminergiques stries et hypothala- L'auteur discute les implications de ces miques est associee chez les vieillards aux changements pour la domaine des pro­ discussion will be restricted to the phenomenes de ralentissement de per­ cessus cognitifs el pour la persistence des literature on normally aging indi­ formance du type Parkinsonien. et aux traces de memoire. viduals and people with presenile and senile dementia, it is noteworthy that a higher than normal incidence of the Dementia refers to a progressive same physical signs have been loss of the mental faculties. The most observed in Down's syndrome common cause of a progressive retardates (Ohara, 1972) and Parkin­ impairment of the mental faculties in son patients (Hirano, 1970). Down's the older adult population is the syndrome retardates develop the degenerative brain disease known as symptoms by age 35 years. In addition senile dementia. If the disease begins to reviewing the physical signs of before the age of 65 years it is referred dementia, the first section of the paper to as presenile dementia or Alzheimer's will discuss the functional implications disease. Presenile and senile dementia of these signs. are diseases of nervous tissue as The second portion of the paper opposed to atherosclerotic dementia describes the chemical and physio­ which is a degenerative disease of the logical correlates of the aging process circulatory system. Together these two and outlines their functional implica­ categories account for the majority of tions. In the third and final section all cases of degenerative brain disease there is a detailed analysis of the in the aged. The incidence of senile behavioral scientist's perspective of dementia is twice as high in women as aging. in men. The proportions are reversed for atherosclerotic dementia (Roth, reported by Kent, 1977). MORPHOLOGICAL SIGNS OF AGING The mental symptoms of senile IN THE BRAIN dementia, from the clinician's Physical evidence for a diagnosis of viewpoint, include flattening of affect, presenile dementia includes the Reprint requests to: Charles Beck. Department of Psychology. Biological Sciences Building. University confusion in spatial and temporal presence in the brain of (I) senile of Alberta, l-dmonton. Alberta. T6G 2E9, Canada. orientation, impairment of memory plaques containing amyloid, an

Supported by a grant from the Medical Research especially for recent events, and a immunoglobulin byproduct; (2) Council. general slowing of movements and tangles of neurofibrils, normally

Krom the Neuropsychology Unit. Department of though processes. The onset is longitudinally arranged in the nerve Psychology. University of Alberta. Edmonton. Alberta. gradual, beginning with a dislike for fiber and thought to participate in the

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transport of vital substances along been related to memory impairments Samorajski, 1975). This results in a neurons; (3) areas of degeneration, in humans (Milner, 1970; Victor et al, reduction in oxygen turnover (Chen et consisting of silver staining granules 1971). The memory deficits of the al., 1972). One would predict from this surrounded by spaces or vacuoles; (4) demented and aged have been a reduced cerebral blood flow with age collections of lipofuscin or age attributed to hippocampal damage and with increasing dementia and this pigment inside neurons, representing (Ball, 1977; Malamud, 1972). Other is indeed the case (Lassen et al., I960; an accumulation of oxidized nerve authors (Brizzee et al., 1974; Scheibel Ingvar and Lassen, 1970; Simard, cell membranes; and (5) loss of nerve et al., 1975, 1976) prefer to emphasize 1971). Slowing of cerebral blood flow cells. the importance of the diffuseness of occurs over the temporal region in the It is widely held that the pervasive­ the signs of physical damage brains of memory impaired senile ness of these signs is positively throughout the brain, in accounting patients, and in the parieto-occipito- correlated with the degree of dementia for general slowing of information temporal region in patients with both for patients stricken before age 65 processing accompanying aging. aphasia symptoms (Hagberg and and for those afflicted later in life Prior to the disintegration of the Ingvar, 1976; Obristetal., 1970). Since (Blessed et al., 1968). However, it is nerve cell body there is an age related old people have a greater arterio­ not generally recognized that virtually deterioration of axonal (output) and venous 02 content difference, all people by 80 years of age present dendritic (input) terminal processes indicating the brain is extracting more similar, though less invidious, ex­ (Bondareff and Geinisman, 1976; 02 per unit of blood (Dastur et al., amples of the same physical pathology Machado-Salas et al., 1977; Scheibel 1963), and since the cerebral capillary (Dayan, 1970; Gellerstedt, 1931; et al., 1975, 1976). network of the senescent brain is more Matsuyama et al., 1966). There is a In summary, morphological changes extensive than that of the younger positive correlation between age in the brain with age provide a picture person (Huziker et al., 1978), the related cell loss, severity of tangle of gradual degeneration and cell loss, diminished cerebral blood flow is formation, and degree of granulo- especially in structures involved in more likely a product of metabolic vacuolar degeneration in both memory. The normal aging process is than morphological variables. normals and dements. However, the accelerated in Alzheimer's disease and In presenile and senile dementia, but yearly rate of cell loss is five times as Down's syndrome. Theories of aging not in atherosclerotic dementia, the great in the Alzheimer patients as in emphasize either the relation between occurrence of neurofibrillary tangles is normal persons (Ball, 1977; Ball and hippocampal degeneration and mem­ proportional to the accumulation of Lo, 1977). ory deficits or that between diffuse aluminum in the brain cells (Crapper degeneration and slowed processing. Brody (1955) hypothesized that the et al., 1976). The concentration of The functional implications of neuro- aluminum in Alzheimer patients is degree of dementia is directly related filbrillary tangles and cell membrane to the incidence of cell loss. Meier- four times that in normal patients instability will be detailed in the next (Crapper, 1974; Crapper et al., 1973). Ruge (1975) suggested that this section of the paper. hypothesis is untenable because Implantation of aluminum into the subsequent studies of senescent rodent brains of animals results in neuro­ brains have revealed less than 1% cell CHEMICAL AND PHYSIOLOGICAL fibrillary tangles indentical to those in losses (Brizzee et al., 1968; Klein and SIGNS OF AGING IN THE BRAIN senile humans' brains (Terry and Michel, 1977). However, these studies The most prominent theory of aging Pena, 1965). Aluminum disrupts examined only the rodent neocortex. is the error catastrophe theory of Orgel protein synthesis in nerve cells (Miller Studies of the old rodent's medial (1963; Comfort, 1974). In all tissue, the and Levine, 1974). The origin of the dorsal nucleus of the thalamus (Stein RNA transcription of the genetic code metabolic error causing the aluminum and Firl, 1976) and hippocampus for protein has an increased error rate accumulation is unknown. (Vijayan, 1977) showed serious with age, resulting in the age related Another anabolic process which degeneration. In humans the physical decline in levels of critical enzymes. deteriorates with aging is that of the signs enumerated above appear in Thus there is an age associated decline synthesis, release, and uptake of many parts of the brain including the in uptake, turnover, and utilization of neurotransmitters. Old brains ex­ neocortex. However, the pathology amino acids and a decline in RNA bio­ perience 25% slower rate and 50% has a predilection for the hippo­ synthesis of enzymes (Tonna and reduced volume of axonal transport of campus and in Alzheimer's disease for Singh, 1976). In general, biochemical substances essential for transmitter the posterior hippocampus in par­ anabolic functions deteriorate production (Geinisman et al., 1977a, ticular (Ball, 1977; Brizee et al., 1974; through the loss of enzymes control­ 1977b), a shortage of the enzymes Gellerstedt, 1931). The magnitude of ling carbohydrate, intermediate necessary for transmitter synthesis the hippocampal cell loss by 70 years protein, and lipid metabolism (McGreer et al., 1977; Spillane et al., of age is fairly substantial. There is (Roberts et al., 1976). With age, a 1977; Vijayan, 1977), an impairment approximately 12% cell loss in decrease occurs in glucose oxidation of waste reducing uptake of unused normals and 60% in presenile dements (Patch, 1977) and in formation and neurotransmitter (Jonec and Finch, (Ball, 1977). Damage to the medial utilization of ATP, an energy source 1975; Sun, 1976), fewer transmitter dorsal thalamus and hippocampus has (Ermini et al., 1971; Sun and receptor binding sites (White et al.,

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1977), reduced number of neurotrans­ 1978; Gygax et al., 1978) and alleviate parietal, temporal, and occipital mitter storage vesicles (Sun, 1976), the complaints of the aged (Bazo, cortices of Alzheimer patients (Perry and lowered sensitivity of the chemical 1973; Hoffbrand et al., 1976). No one et al., 1977). Normal old people do not response of the receiving neuron to has described the effects of the ergot experience significant declines in delivered neurotransmitter (Govoni et alkaloids on the physical signs of acetylcholine enzyme levels outside al., 1977, Spano et al., 1975). cerebral senescence. the hippocampus (Perry et al., 1977). Conversely, products which de­ Dopamine is released by certain The dysfunction in Alzheimer patients grade or catabolize neurotransmitters nerve terminals in the retina in re­ is presynaptic, i.e., in acetylcholine increase with aging. Acid phos­ sponse to light (Kramer, 1971). In aged synthesis, rather than an impairment phatases, perioxidases, monamine mammals the cells receiving the in postsynaptic receptor site sensitivity oxidase, and catechol-o-methyl trans­ dopamine become hypersensitive to (Perry etal., 1977; Spillaneetal., 1977; ferase all increase in the old brain released dopamine (Spano et al., 1975) White et al., 1977). Such abnormality (Broch, 1973; Brunk and Ericcson, in an attempt to compensate for is consistent with electron microscopic 1972; Robinson et al., 1977). The latter functional dopaminergic dennerva- evidence of gross degenerative changes two molecules degrade the cate­ tion (Govoni et al., 1977). It is possible in presynaptic structures and the cholamine transmitters, dopamine that such paradoxical hypersensitivity normal appearance of receptor mem­ and norepinephrine. may contribute to the longer dark branes (Wisniewski and Terry, 1976). adaptation time (Reading, 1968) and The greater the depletion of the choli­ If the neurotransmitter changes nergic enzyme, the greater the degree referred to above affected systems the increased aggravation from light of neurofibrillary tangles evident controlling behaviors which deteri­ glare (Wolf, 1960) experienced by old (White et al., 1977). Geinisman et al. orated with age, then it is apparent people. Usually the effects are (1977a, 1977b) suspect that the tangles that the behavioral deficits of the aged attributed to increased opacity of the may be partly responsible for the re­ would be ascribable to metabolic lens and cornea. dysfunction rather than frank cell loss duced availability of the enzyme at Calcium ion concentrations in­ presynaptic membranes. as the primal causal agent. The crease in muscle (Gutmann and evidence for this view is growing. The Hanzlikova, 1972) and nervous tissue In response to stress, the medulla of aging brain undergoes a significant with aging (Sun and Seaman, 1977). the adrenal gland liberates a number decline in the functional effectiveness This may be related to abnormally low of neurotransmitter substances into of the dopamine system in the striatum levels of parathyroid hormone in the the blood stream. The urinary and (Finch, 1973; Govoni et al., 1977; senescent (Fujita et al., 1976). Calcium blood plasma levels of epinephrine, McGeer et al., 1977; Robinson et al., plays an important role in neurotrans­ norephinephrine, and dopamine beta- 1977). There is also a decrease in the mitter release. The redressing of the hydroxylase increase with age number of cells in the substantia nigra Ca^ imbalance has been suggested as (Freedman et al., 1972; Giorginoet al., with age (McGeer et al., 1977). the mechanism underlying the efficacy 1969; Kvetnansky et al., 1978) as does Behaviorally, this would mean that the of chronic chlorpromazine therapy in the size of adrenal medulla (Kvetnan­ normal aging process would move reducing neuronal lipofuscin accumu­ sky et al., 1978; Sotgiu et al., 1960). people toward the Parkinsonian ratio lation (Samorajski and Rolsten, 1976). Hyperfunction of the adrenal medulla of excess acetycholine to dopamine in Chlorpromazine has multiple effects in the aged coupled with their the critical system linking the sub­ on release and uptake of dopamine exaggerated sensitivity to its hor­ stantia nigra and the striatum and norepinephrine. mones (Frolkis et al., 1972) may be (McGreer et al., 1977). Thus one related to increased incidence of would expect slowness of movement, Chemical blocking of pathways hypertension, atherosclerosis, and rapid fatiguing, tardy movement requiring the neurotransmitter acetyl­ cardiac infarction in old people initiation, loss of associated move­ choline impairs performance on (Kvetnansky et al., 1978). ments, and diminished kinetic grace, memory tests. The deficits were similar characteristic of Parkinson patients, to those observed in normal old The hippocampus is capable of in­ to become more obvious with persons (Drachman and Leavitt, hibiting the secretion of adreno- advancing age. Evidence that the same 1974). Many neurons terminating in corticotrophic hormone from the dopaminergic deficit may be responsi­ the hippocampus release acetyl­ anterior pituitary. This hormone ble for a flattening of affect and a loss choline. There is a significant age controls secretions of other hormones, of incentive motivation is available related decline in the hippocampal e.g., corticosterioids, from the cortex (Phillips and Fibiger, 1973). concentration of the enzyme necessary of the adrenal gland. Neurons of the for acetylcholine synthesis (Perry et hippocampus have receptor sites for The ergot alkaloids, e.g., dihydro- al., 1977; Vijayan, 1977). This decline one of the corticosteriods, namely ergotoxine, which stabilize the is even more marked in Alzheimer corticosterone. Corticosterone modu­ terminal membranes of dopaminergic patients, but not in chronic schizo­ lates the genetic processes governing neurons (Goldstein et al., 1978; Spano phrenics, chronic unipolar depres- anzyme synthesis in the hippocampus and Trabucchi, 1978) protect the sives, or multi-infarct dements. It is (Lee et al., 1977). These enzymes are organism against the metabolic effects significant in degree not only in the necessary for neurotransmitter pro­ of reduced blood flow (Boismare et al.. hippocampus but also in the frontal, duction and, as noted above, are

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depleted in old age (Perry et al., 1977). suggests that the speeded and memory hypofunction of the dopaminergic There is a positive correlation between categories of subtests are measuring system discussed above. McGeer's the degree of hippocampal neuron de­ the same thing. For example, memory (1977) hypothesis was that the generation in the individual and the tests would produce "speed" deficits if dopaminergic bias in the aged is resting levels of corticosterone in the the pace of stimulus presentation and toward that of the Parkinsonian blood plasma (Landfield and Lynch, response production is too rapid for neuropathology. Parkinson patients 1977). Resting plasma corticosterone the old person. When taken to exhibit not only slowed movement level decreases in old age. Continued identical original learning criteria, times but also slowed pre-electromyo- degeneration of the hippocampus with young and old are no different on graphic reaction times (Brumlick and senescence may result from increased subsequent recall (Hulicka, 1965). Boshes, 1966). Parkinson patients sensitivity to the circulating hormones When allowed to pace themselves, the persist in an error response for a longer (Frolkis et al., 1972). It would be elderly took longer to learn the task duration on tracking tasks than do interesting to measure corticosterone than did young persons but did just as normal individuals (Angel et al., 1970; levels and sensitivity in Alzheimer well as the young on recall tests Bowen et al., 1972). The degree to patients. (Adamowicz, 1976). Total learning which simple stimuli persist in In summary, the senescent brain time available rather than rate of memory, as measured by the critical experiences dysfunctional biases presentation is the critical variable flicker fusion test, increases with toward the Parkinsonian state of (Winn and Elias, 1977). increasing severity of Parkinson striatal dopamine depletion and If the slowed processing were a movement dysfunction (Riklan et al., consequent slowing of movement as general characteristic, one would 1970). Personality inflexibility as well as toward mnemonic impairment expect an increased deficit with the measured by the F-Scale increases in precipitated by hypofunction of the amount of information processed on the same manner (Ploski et al., 1966). hippocampal and cortical cholingergic verbal tasks (Anders and Fozard, Comparable examples of stimulus systems. A common age related 1973; Klauser and Klein, 1978) and on trace persistance and response mode deterioration of the genetically nonverbal tasks (Benton, 1977; persistance for the aged will be controlled transcription of protein Fozard et al., 1976); slowed retrieval described below. may underly both trends. search of both primary and secondary Another mechanism that may memory (Anders and Fozard, 1973), contribute to slowed processing is and slowed rotation and comparison RELATED BEHAVIORAL SIGNS dysfunction of the hippocampal of spatial depth figures (Gaylord and OF AGING cholinergic system. Damage to the Marsh, 1975). The studies cited have Whether intelligence as defined by hippocampus causes the organism to demonstrated these effects with the fail to adjust to changing reinforce­ the traditional intelligence test does normal aged. decline with age (Birren and Morrison, ment contingencies and to fail to 1961; Williams, 1970) or does not Partitioning of the total response habituate to novel stimuli (Kimble, (Barton et al., 1975; Ford and Roth, time into reaction time and movement 1968). The organism tends to persist in 1977; Schaie et al., 1973) appears to time revealed that both were slow in performing current or habitual modes depend on methodological issues the aged and that the reaction time was of responding. It is possible that the which are not central to theme of this responsible for the greatest part of the slowness of the aged is partly the result review. Two main categories of deficit (Spirduso, 1975). Retarded of a tendency to prolong the response subtests in these and more recent movement time was attributable to to internally or externally generated batteries (Branconnier and Cole, 1978; slower peripheral nerve conduction stimuli (Axelrod, 1963; Botwinick, Shader et al., 1974) appear to be age velocity (Retzlaff and Fontaine, 1965), 1973). If the subsidence of the neural sensitive. These are speeded subtests loss of muscle fiber mass (Gutmann response to the initial stimulus is slow, and the memory subtests. and Hanzlikova, 1976), decreased the perception of the second stimulus The memory deficit of the aged is frequency of miniature end-plate would be retarded and slowed not specific for any particular potentials and slowed contraction processing of information would mnemonic subfunction such as coupling time (Gutmann and Hanzli­ result. If this were the case one would memory storage capacity (Eber, 1976; kova, 1972). look for evidence in the aged of the cf. Salthouse, 1978); level of memory Several mechanisms may contribute persistance of brief images at the processing (Eysenck, 1974; Zelinski et to the slowed reaction time. Raised registration level and for the per­ al., 1978; cf. Mergler et al., 1977); sensory thresholds (Clark and Mehl, severation of sets at the cognitive level. ignoring irrelevant stimuli (Rabbitt, 1971; Dyck et al., 1972, 1974; Harkins Exaggerated persistance of the 1965; cf. Klauser and Kleim, 1978); and Chapman, 1976; Kokmen et al., iconic trace has recently been registration as opposed to retrieval 1978; Whanger and Wang, 1974) and demonstrated to result in superior (Adamowicz, 1976), or on long versus slowed conduction time of brain performance in the recognition of short delays of recall (Schneider et al., neurons would at best contribute 10% fragmented words in the aged 1975). Rather, the deficit seems to be a to the total retardation of the reaction compared to the young (Kline and general slowing of information time (Retzlaff and Fontaine, 1965). A Orme-Rogers, 1978). Complementary processing (Adamowicz, 1976). This more significant factor would be the halves of a single word were flashed on

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a screen one after the other. If the may modulate cognitive deficits in the cessing, but that slowing may occur as persistance of the trace of the initial elderly (Birkhill and Schaie, 1975; a result of other causes, for example word half in the mind of the viewer was Hoyer et al., 1973; Plemons et al., excessive caution (Birkhill and Schaie, superimposed on the flash of the 1978). Physical exercise seems 1975). second half of the word, recognition of definitely to influence physiological the word would result. Old people performance (Retzlaff and Fontaine, REFERENCES were especially superior for the longer 1965; de Vries, 1971) and reaction time ADAMOW1CZ, J. K. (1976). Visual short-term intervals between word fragments. In (Spirduso, 1975; Spirduso and memory and aging. Journal of Gerontology addition, old persons show enhanced Clifford, 1978). The last study is 31. 39-46. persistance of complementary after­ especially provocative since exercising ANDERS. T. A. and FOZARD. J. I.. (1973). images (Kline and Nestor, 1977), and, men in their sixties performed with Effects of age upon retrieval from primary as one might expect, poor temporal reaction times comparable to men in and secondary memory. Developmental resolution of shocks to the skin their twenties. One would like to know Psychology 9. 411-415. ANGEL. R. A.. ALSTEN, VV. and HIGGINS, (Axelrod et al., 1968), slowed what would be the iconic trace per­ J. R. (1970). Control of movement in Park­ temporal processing of auditory sistance times and retrieval search inson's disease. Brain 93. 1-15. stimuli (Corso, 1975), lowered visual times of those active oldsters. AXELROD, S. (1963). Cognitive tasks in several critical flicker fusion thresholds modalities. In Processes of Aging, edited by (Misiak, 1951; McFarland et al., In conclusion, evidence has been R. H. Williams. C. Tibbitts and W. Donahue, 1958), lowered auditory click fusion presented for an age dependent Atherton Press, New York, Vol. 1, pp. 132- thresholds (Weiss, 1959), protracted slowing of information processing. 145. susceptibility to backward masking Such an impairment may relate to AXELROD, S., THOMPSON. L. W. and persistance of sensory traces and COHEN, L. D. (1968). Effects of senescence (Kline and Szafran, 1975), and longer on the temporal resolution of somesthetic lasting visual evoked responses to perseveration of cognitive sets. stimuli presented to one hand or both. photic stimulation (Mundy-Castle, Persistance would be an advantage Journal of Gerontology 2. 191-195. 1953). It is easy to see how such only in tasks in which retention of a BALL, M. J. (1977). Neuronal loss, neurofibril­ persistance, if also applicable to items single item or mode of response was lary tangles and granulovascular degeneration in the hippocampus with aging and dementia. retrieved from primary of secondary required. Serial search or serial learning tasks would produce deficits A quantitative study. Acta Neuropathologica memory, would slow down retrieval 37. 11-118. search time (Anders and Fozard, in performance, unless there was adequate time for shifts between items. BALL. M. J. and LO. P. (1977). Granulovacuo- 1973). lar degeneration in the aging brain and in Evidence has been presented that dementia. Journal of Neuropathology and When one speaks of secondary and dysfunction in dopaminergic and Experimental Neurology. 36, 474-487. permanent memory one usually cholinergic brain systems may underly BARTON. E. M.. PLEMONS, J. K.. WILLIS. speaks of perseveration of sets rather these persistance effects. Avenues for S. L. and BALTES. P. B. (1975). Recent findings on adult and gerontological than persistance of traces. Old people future research suggest themselves. intelligence: changing a stereotype of perseverate in viewing ambiguous Persistance measures have not been decline. American Behavioral Scientist 19, figures in only one mode (Botwinick et applied to the other types of human 224-236. al., 1959), persist in viewing the Necker abiotrophies (Bowen et al., 1976) or BAZO, A. G. (1973). An ergot aklaloid prepar­ cube in only one view (Heath and their animal models (Crapper, 1974; ation (hydergine) versus papaverine in Orbach, 1963), and fail to reverse the Ungerstedt, 1971). One disturbing treating common complaints of the aged: a double blind study. Journal of American figure ground relationship in order to possibility is that schizophrenia which Geriatric Society 21. 63-71. read ambiguous words (Kline et al., supposedly has a dopaminergic bias BENTON, A. L. (1977). Interactive effects of 1977). Tasks requiring a shifting of opposite in direction to that of age and brain disease on reaction time. problem solving set are expecially Parkinsonism is also said to be Archives of Neurology 34. 369-370. taxing for the aged (Botwinick et al., characterized by slow information BIRKHILL. W. R. and SCHAIE. K.W.( 1975). 1957, 1958, 1959; Goodrick, 1972; processing (Davidson and Neale, The effect of differential reinforcement of Heglin, 1956). Old people have 1974; Saccuzzo et al., 1974; Yates, cautiousness in intellectual performance among the elderly. Journal of Gerotology anecdotally described the persistance 1966; Yates and Korboot, 1970) and 30. 578-583. with which unwanted tunes and trace persistance (Gruzelier et al., B1RREN.J. E.and MORRISON. D. K. (1961). thoughts run through their minds. 1972). It would be helpful to know Analysis of the WAIS subtests in relation to What can be done to postpone the whether the persistence measures in age and education. 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