- Email: [email protected]
Dementia: Overview
Dementia: Oeriew Berndt E, Christensen L 1974 Testing for the existence of an aggregate index of labor inputs. American Economic Reiew 64: 391–404 Cobb C, Douglas P 1928 A theory of production. American Economic Association, Papers and Proceedings 18: 139–65 Davis S J, Haltiwanger J 1992 Gross job creation, gross job destruction, and employment reallocation. Quarterly Journal of Economics 107: 819–65 Griliches Z 1969 Capital-skill complementarity. Reiew of Economics and Statistics 51: 465–8 Hamermesh D S 1993 Labor Demand. Princeton University Press, Princeton, NJ Hamermesh D S, Pfann G A 1996 Adjustment costs in factor demand. Journal of Economic Literature 34: 1264–92 Hamermesh D, Trejo S 2000 The demand for hours of labor: direct evidence from California. Reiew of Economics and Statistics 82: 38–47 Hart R 1987 Working Time and Employment. Allen and Unwin, Boston Hunt J 1999 Has work-sharing worked in Germany? Quarterly Journal of Economics 114: 117–48 Marshall A 1920 Principles of Economics, 8th edn. Macmillan, New York Oi W 1962 Labor as a quasi-fixed factor of production. Journal of Political Economy 70: 538–555 Rosen S 1968 Short-run employment variation on class-I railroads in the U.S., 1947–63. Econometrica 36: 511–29 Saavedra J, Torero M 1998 Labor Market Regulation and Employment in Peru. GRADE, Lima, Peru
D. S. Hamermesh
Dementia: Overview Dementia is a medical condition which is characterized by a generalized mental deterioration. The word has Latin roots, ‘de’ meaning separation, cessation or contraction, and ‘meme’ meaning ‘mind.’ Therefore, in dementia there is a cessation or contraction of the mind. The usage of the term dementia can be traced back to the Roman writer and encyclopedist, Aulus Cornelius Celsus in the first century AD. Celsus distinguished dementia, a chronic ‘contraction of the mind,’ from acute conditions such as delirium. The first medical identification of aging with dementia can be traced to Aretaeus of Cappadocia in the second century AD. He distinguished a condition which began in old age and continued until death, characterized by ‘a torpor of the senses, and a stupefaction of the gnostic and intellectual faculties’ (Adams 1861). Galen, perhaps the most influential physician of all time, also identified old age as a cause of dementia in the second century AD. He defined ‘morosis’ as a condition in which ‘the knowledge of letters and other acts are totally obliterated, indeed they can’t even remember their own names’ (Galen 1821–33 trans-
lation). One condition associated with morosis was old age. No further advances in the clinical description of dementia appear to have been made for more than 1500 years. In 1793, the eminent American physician, Benjamin Rush, a signer of the United States Declaration of Independence and author of the first American textbook of psychiatry, a man who is credited by the American Psychiatric Association with being the father of American psychiatry, added to the clinical description of dementia. He noted that: it would be sufficiently humbling to human nature if our bodies exhibited in old age the marks only of a second childhood, but human weakness descends even lower. I met with an instance of a woman between 80 and 90 who exhibited the marks of a second infancy, by such a total loss of her mental faculties as to lose all consciousness in discharging her alvine and urinary excretions. In this state of the body, a disposition to sleep succeeds the wakefulness of the first stages of old age’ (Rush 1793).
The accuracy of Benjamin Rush’s description has become increasingly apparent over the past two centuries. The modern term, ‘senile dementia,’ is derived from Esquirol (1838), who described this condition in a French textbook of psychiatry. He noted that this is a condition in which there occurs a weakening of the memory for recent experience and a loss of drive and will power. He noted that senile dementia (in French, deT mence senile), appears gradually and may be accompanied by emotional disturbances. In modern usage, the term dementia refers to either: (a) any condition associated with a generalized mental deterioration, or (b) a progressive generalized mental deterioration, frequently occurring in later life. Both usages are commonly applied.
1. Progressie Dementia The most important progressive dementia is Alzheimer’s disease, which plays a role in a majority of cases (Tomlinson et al. 1970). Other progressive dementias include cerebrovascular dementia, Lewy body dementia, and the frontotemporal dementias. With the exception of the frontotemporal dementias, these conditions increase in occurrence with increasing age. Consequently, the modern increase in lifespan in most regions throughout the world has been accompanied by a dramatic increase in the occurrence of these conditions (Henderson and Jorm 2000).
1.1 Alzheimer’s Disease Alzheimer’s disease (AD) is one of the most devastating medical conditions of contemporary times. 3389
Dementia: Oeriew Table I Global Deterioration Scale (GDS) for age-associated cognitive decline and Alzheimer’s disease1 GDS stage 1 2
3
4
5
3390
Clinical characteristics No Subjective complaints of memory deficit. No memory deficit evident on clinical interview. Subjective complaints of memory deficit, most frequently in following areas: (a) Forgetting where one has placed familiar objects; (b) Forgetting names one formerly knew well. No objective evidence of memory deficit on clinical interview. No objective deficit in employment or social situations. Appropriate concern with respect to symptomatology. Earliest clear-cut deficits. Manifestations in more than one of the following areas: (a) Patient may have gotten lost when traveling to an unfamiliar location. (b) Co-workers become aware of patient’s relatively poor performance. (c) Word and/or name finding deficit become evident to intimates. (d) Patient may read a passage or book and retain relatively little material. (e) Patient may demonstrate decreased facility remembering names upon introduction to new people. (f) Patient may have lost or misplaced an object of value. (g) Concentration deficit may be evident on clinical testing. Objective evidence of memory deficit obtained only with an intensive interview. Decreased performance in demanding employment and social settings. Denial begins to become manifest in patient. Mild to moderate anxiety frequently accompanies symptoms. Clear-cut deficit on careful clinical interview. Deficit manifest in following areas: a Decreased knowledge of current and recent events. b May exhibit some deficits in memory of one’s personal history. c Concentration deficit elicited on serial subtractions. d Decreased ability to travel, handle finances, etc. Frequently no deficit in following areas: (a) Orientation to time and place. (b) Recognition of familiar persons and faces. (c) Ability to travel to familiar locations. Inability to perform complex tasks. Denial is dominant defense mechanism. Flattening of affect and withdrawal from challenging situations. Patient can no longer survive without some assistance. Patient is unable during interview to recall a major relevant aspect of their current life, e.g.: a Their address or telephone number of many years. b The names of close members of their family (such as grandchildren). c The name of the high school or college from which they graduated.
Diagnosis and prognosis2,3 Normal Adult Age associated memory impaired (sometimes termed normal aged forgetfulness or aged-associated cognitive decline) 15% develop dementia within 4 years2 Mild cognitive impairment Two-thirds develop dementia within 4 years2
Mild Alzheimer’s disease Mean duration: 2 years
Moderate Alzheimer’s disease Mean duration: 1.5 years
Dementia: Oeriew Table I Continued GDS stage
6
7
Clinical characteristics
Diagnosis and prognosis2,3
Frequently some disorientation to time (date, day of the week, season, etc.) or to place. An educated person may have difficulty counting back from 40 by 4s or from 20 by 2s. Persons at this stage retain knowledge of many major facts regarding themselves and others. They invariably know their own names and generally know their spouse’s and children’s names. They require no assistance with toileting or eating, but may have difficulty choosing the proper clothing to wear. May occasionally forget the name of the spouse upon whom Moderately severe Alzheimer’s disease they are entirely dependent for survival. Mean duration: 2.5 years Will be largely unaware of all recent events and experiences in their lives. Retain some knowledge of their surroundings; the year, the season, etc. May have difficulty counting by 1s from 10, both backward and sometimes forward. Will require some assistance with activities of daily living: (a) May become incontinent. (b) Will require travel assistance but occasionally will be able to travel to familiar locations. Diurnal rhythm frequently disturbed. Almost always recall their own name. Frequently continue to be able to distinguish familiar from unfamiliar persons in their environment. Personality and emotional changes occur. These are quite variable and include: a delusional behavior, e.g., patients may accuse their spouse of being an imposter; may talk to imaginary figures in the environment, or to their own reflection in the mirror. b obsessive symptoms, e.g., person may continually repeat simple cleaning activities. c anxiety symptoms, agitation, and even previously non-existent violent behavior may occur. d cognitive abulia, e.g., loss of willpower because an individual cannot carry a thought long enough to determine a purposeful course of action. All verbal abilities are lost over the course of this stage. Severe Alzheimer’s disease Early in this stage words and phrases are spoken but speech is Mean time to demise: 2–3 years very circumscribed. Potential for survival: 7 or Later there is no speech at all—only unintelligible vocalizations. more years Incontinent; requires assistance toileting and feeding. Basic psychomotor skills (e.g., ability to walk) are lost with the progression of this stage. The brain appears no longer to be able to tell the body what to do. Generalized and cortical neurologic signs and symptoms are frequently present.
1. Reisberg B, Ferris S H., de Leon M J, & Crook T. 1982 The global deterioration scale for assessment of primary degenerative dementia. American Journal of Psychiatry 139: 1136–1139. Copyright 1983 by Barry Reisberg, M.D. 2. Kluger A, Ferris S H, Golomb J, Mittelman, M S, Reisberg B 1999 Neuropsychological prediction of decline to dementia in nondemented elderly. Journal of Geriatric Psychiatry and Neurology 12: 168–79. 3. Reisberg B, Franssen E, Shah M A, Weigel J, Bobinski M, Wisniewski H M 2000 Clinical diagnosis of dementia: A review. In: Maj M, Sartorius N (eds.) Dementia, WPA Series, Evidence and Experience in Psychiatry, Wiley, Chichester, UK, Vol. 3, pp. 69–115.
3391
Dementia: Oeriew For example, in the United States, the number of persons in nursing homes and related institutions with AD exceeds the total number of persons in all hospitals and related institutions. Consequently, the institutional burden of AD in the United States is approximately the same as the institutional burden of all other illnesses combined. Worldwide, AD is estimated to afflict more than 15 million persons, and the prevalence continues to increase with increasing life expectancy of the world’s people. The precise mechanism of the cause of AD is unknown. However, particular genotypes which predispose to early onset AD have been identified. These genetic ‘defects’ are β-amyloid precursor protein mutations located on chromosome 21, presenilin 1 mutations located on chromosome 14, and presenilin 2 mutations which are located on chromosome 1. Some investigators point out that each of these mutations is associated with increased production of β-amyloid protein, one of the neuropathologic hallmarks of AD (Selkoe 1997). However, the presenilin mutations in particular, have been related to a variety of other pathologies apart from increased β-amyloid protein. Further evidence for the role of β-amyloid in the etiopathogenesis of AD is the observation that persons with Down’s syndrome develop Alzheimer’s pathology early in life and carry an extra copy of the βamyloid precursor protein gene resulting in excess βamyloid production. The occurrence of the common late-life form of AD has also been associated with particular genotypes. The most clearly identified gene which influences the occurrence of late life, also known as ‘sporadic’ Alzheimer’s disease, is the apolipoprotein E (apoE) gene (National Institute on Aging \Alzheimer’s Association Working Group 1996). Caucasians who carry the apoE4 allele are at increased risk for AD in later life. Caucasians who are homogenous for apoE4 have as much as eight times the risk of AD as similarly aged persons who do not carry the apoE4 allele. Other genes and gene interactions which influence the occurrence of the common, late-life form of AD have not yet been fully elucidated. Although the mechanism by which AD occurs is not known, a characteristic clinical course of AD has been described (Reisberg et al. 1982, 2000). This characteristic clinical course is accompanied by characteristic neuropathologic manifestations and a characteristic neuropathologic progression. Clinically, AD can be described on a continuum with the changes in what is now termed normal aging, progressing to mild cognitive impairment (MCI) and subsequently to AD. This clinical continuum is illustrated in terms of the cognitive, functional and emotional progression of aging and AD in Table 1. Functionally, the progression of brain aging, MCI and AD can be described in even greater detail, in terms which are universally clear to both lay persons and professionals. This characteristic functional progres3392
sion is familiar to many observers because it reverses the sequence of functional acquisition in human development, a phenomenon which has been termed ‘retrogenesis’ (Table 2) (Reisberg et al. 1999, 2000) The hallmark neuropathologic manifestations of AD are extracellular senile plaques which contain the β-amyloid protein, and intracellular neurofibrillary tangles which contain the protein tau (see Alzheimer’s Disease, Neural Basis of ). Very strong relationships have been found between the clinical progression of AD and the progression of pathology in the hippocampus, a brain region which has been notably associated with memory. Progressive pathologic manifestations in the hippocampus include neurofibrillary pathology, volume loss, and neuronal cellular loss. Although the hippocampus is a brain region which manifests early and progressive AD pathology, AD is a generalized brain disease with, for example, progressive decrements in brain glucose utilization (energy metabolism) and progressive slowing of brain wave electrical activity on the electroencephalogram, as well as neuropathologic manifestations in numerous brain regions, which become particularly evident as AD progresses. Neuropathologic stages of AD have been described (Braak and Braak 1991). These are transentorhinal stages I and II, limbic stages III and IV, and neocortical stages V and VI. Each of these stages of Braak and Braak are based upon the evolution and spread of neurofibrillary pathology in the brain of the AD patient. Braak and Braak (1996) and Reisberg et al. (1992, 1999) have described a common basis for the neuropathologic and clinical manifestations of AD. This is the progressive involvement of the most recently, and therefore the most thinly, myelinated brain regions, followed by progressively more thickly myelinated, and therefore, better protected, brain regions. The most thickly myelinated brain regions subsume the functions and associated cognitive skills, which are the first to be acquired in the course of human development. Conversely, the most thinly myelinated brain regions subsume the most recently acquired functions and associated cognition. These recently myelinated regions are the most vulnerable to AD pathology. Consequently, cognitive and functional skills which are the most recently acquired are the most vulnerable to AD pathology, and those cognitive and functional skills which are the first to be acquired in normal human development are the last to be lost with the progression of AD. In brief, last in, first out. This retrogenesis phenomenon, which is illustrated for functional skills in Table 2, also applies to cognition and many aspects of brain physiology, including neurologic reflexes and apparently, to at least some extent, brain electrophysiology and metabolism. Very recently it has been demonstrated that the β-amyloid, the major putative toxic pathology in AD is destructive to the oligodendroglia, the brain cells
Table 2 Retrogenesis: functional landmarks in normal human development and Alzheimer’s disease (AD) Normal Development Approximate Total Duration: 20 years Approximate age Adolescence 13–19 years Late childhood 8–12 years Middle childhood 5–7 years Early childhood 5 years 4 years 4 years 3–4.5 years 2–3 years Infancy 15 months 1 year 1 year 6–10 months 2–4 months 1–3 months
Approximate duration in development
Acquired abilities
Alzheimer’s Degeneration Approximate Total Duration: 20 years
Lost abilities
Alzheimer stage
Approximate duration in AD
Developmental age of AD
7 years
Hold a job
Hold a job
3 – Incipient
7 years
19–13 years: Adolescence
5 years
Handle simple finances
Handle simple finances
4 – Mild
2 years
12–8 years: Late childhood
2.5 years
Select proper clothing
Select proper clothing
5 – Moderate
1.5 years
7–5 years: Middle childhood
4 years
Put on clothes unaided
Put on clothes unaided
2 years
5–2 years: Early childhood
Shower unaided Toilet unaided Control urine Control bowels
Shower unaided Toilet unaided Control urine Control bowels
6a – Moderately severe b c d e
Speak 5–6 words
Speak 5–6 words
7a – Severe
7 years or longer
15 months to birth: Infancy
Speak 1 word Walk Sit up Smile Hold up head
Speak 1 word Walk Sit up Smile Hold up head
b c d e f
1.5 years
Copyright # 1984, 1986, 1996, 2000 by Barry Reisberg, M.D. All rights reserved.
3393
Dementia: Oeriew which produce the myelin (Xu et al. 2001). ApoE, the AD risk-determining factor, is a molecule associated with cholesterol transport. ApoE has been shown to affect neuronal repair mechanisms and the apoE3 allele appears to have a greater neuroprotective effect than the apoE4 allele (Poirier et al. 1993; Buttini et al. 1999). Therefore, a common basis for the molecular, pathologic, and clinical manifestations of AD can be postulated although many elements of the precise pathogenic mechanism remain unknown.
1.2 Vascular Dementia Formerly, this entity was designated multi-infarct dementia because of its strong relationship to strokes, both large and small (Hachinski et al. 1974). Although originally considered by Hachinski to be a stroke-like entity with an abrupt onset and stepwise pattern of deterioration, this deterioration pattern is rarely observed. Vascular dementia is now thought to be a condition marked by progressive decline in cognition and functioning in which cerebrovascular, i.e., stroke risk factors, play a major role. These risk factors include hypertension and cardiovascular disease, as well as more overt evidence of cerebrovascular disease such as transientischemic attacks and focal neurologic signs and symptoms. In most cases, vascular dementia occurs in association with Alzheimer’s brain pathology, a condition which is sometimes termed ‘mixed dementia.’ Much less frequently, vascular dementia appears to occur without evidence of concurrent AD. Consequently, many investigators view vascular dementia as on a continuum with AD. This continuum concept has become particularly compelling in recent years, since virtually all of the elements associated with vascular dementia have been shown to be risk factors for so-called ‘pure AD.’ In accordance with the concept of an additive morbidity of vascular dementia and AD, the course of vascular dementia has been found to be generally more rapid than AD. Vascular dementia is generally considered to be the most common dementia entity after AD.
1.3 Lewy Body Dementia Lewy bodies are spherical inclusions located in the cytoplasm of neurons which characteristically contain a protein known as α-synuclein. Originally Lewy bodies were considered to be a prominent feature of Parkinson’s disease and were not associated with late life dementia. However, new staining techniques in the 1990s indicated that Lewy bodies in the brain stem and the cortex commonly occur in dementia patients studied postmortem. Estimates indicate that as many 3394
as 15 to 25 percent of dementia patients manifest Lewy bodies at the time of demise (McKeith et al. 1996). However, in the great majority of these cases, Lewy bodies exist together with neuropathologic manifestations of AD and\or vascular dementia. When this mixed neuropathology occurs, the clinical manifestations of the dementia are those of AD and\or vascular dementia, and there is no distinctive Lewy body dementia clinical syndrome. In approximately 4 percent of all dementia cases coming to autopsy, Lewy bodies occur in the brain in the absence of other dementia disorders. In these cases, a classical Lewy body dementia (LBD) clinical syndrome occurs. This syndrome is marked by three core features, any\or all of which may be present: (a) a relatively fluctuating clinical course, with variability in cognition; (b) the presence of vivid, well formed, visual hallucinations; and (c) the presence of Parkinsonian features. Another important aspect of LBD is sensitivity to neuroleptic (antipsychotic) medications, particularly those known to be associated with Parkinsonian side effects (Ballard et al. 1998). In general, the onset of LBD is more acute than the onset of AD, and the course of LBD appears to be shorter than that of AD.
1.4 Frontotemporal Dementias These are a diverse group of disorders for which various classification schemata have been developed. For example, biomolecular categorizations have been developed recently which are extremely useful in categorizing one subgroup of frontotemporal dementias, those with frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17) (Foster et al. 1997). The FTDP-17 dementias are characterized by mutations which alter tau, the protein responsible for neurofibrillary changes such as those found in AD. Another frontotemporal dementia type marked by abnormal tau accumulation is Pick’s disease. In Pick’s disease there is an intracellular inclusion known as the Pick body which contains tau accumulations as well as other substances. Other forms of frontotemporal dementia are classified mainly on the basis of their clinical presentation. They include semantic dementia (see Dementia, Semantic), progressive aphasia, and motor neuron disease dementia. The core clinical features of the frontotemporal dementias have been described in part as disinhibition, decreased insight, apathy, disorganization, lack of personal hygiene, mental rigidity, and hyperorality (Brun et al. 1994, Kertesz 2000). In addition, aphasia and other language disturbances are frequently present. Like the basic pathologic disturbances, these behavioral manifestations are very heterogenous and occur on a clinical spectrum. In general, the frontotemporal dementias occur in adults at a younger age than AD. Some believe that
Dementia: Oeriew these conditions are very common in patients who are institutionalized for mental illness.
1.5 Other Progressie Dementias Various other diverse conditions produce progressive dementia. In general, these other conditions are believed to be considerably less common than the dementias which have been reviewed more specifically in the preceding sections. Perhaps the most notable of these other dementias are the prion dementias, of which the most frequent is Creutzfeldt-Jakob disease (CJD). Prion dementias are believed to result from a self-propagating conformational change in a protein, known as the prion protein. This prion, a proteinaceous infective agent, can be acquired either spontaneously or through transmission of biologic materials containing the prion, including brain, pituitary glandular substance, and corneal lens transplants. Spontaneous CJD occurs in approximately one person per million population worldwide. Recently, a form of transmissible CJD arose in Britain as a result of transmission of a prion disease in cattle to humans. This ‘epidemic’ which has affected dozens of persons in Britain and, more recently, several persons on the European continent, has resulted in the destruction of the entire British cattle herd and a change in dietary habits of tens of millions of persons in Europe and elsewhere. Consequently, although the prion dementias remain rare conditions in humans, the threat of the spread of these proteinaceous infections, has caused somewhat justified alarm, in particular in Europe, but also throughout the world. Other relatively uncommon progressive dementias include progressive supranuclear palsy, and corticobasilar degeneration. These conditions, like some of the frontotemporal dementias, are marked by abnormal tau protein and resultant neurofibrillary accumulations. There are also many progressive dementias associated with broader pathologic spectra, of which dementia is only one element. Among these are the dementia of Down’s syndrome, the dementia of normal pressure hydrocephalus (NPH), and the dementia of Huntington’s disease. Some of these dementias are very closely related to AD dementia. For example, persons with Down’s syndrome universally develop an Alzheimer’s type neuropathologic and clinical picture at a relatively early age in comparison with persons with classical AD. Similarly, brain biopsy studies have recently demonstrated that many elderly persons with NPH who manifest a dementia component to the clinical syndrome, show Alzheimer’stype pathology, specifically neuritic plaques, upon brain tissue examination (Golomb et al. 2000). As is the case for AD, the percentage of NPH dementia patients with biopsies demonstrating neuritic plaques
increases with dementia severity, rising from about 20 percent of patients with MCI to about 75 percent of patients in stage 6 and 7 of the global deterioration scale (see Table 1). These studies indicate that the gait disturbance which is characteristic of NPH appears to be associated with dilated cerebral ventricles (i.e., expansion of the fluid filled cavities in the brain), whereas the dementia component of NPH is probably related to concomitant AD.
2. Dementias with Variable Prognoses Numerous diverse physiologic disturbances can produce dementias which may be acute or chronic, reversible or permanent. These diverse conditions include infectious conditions, toxins, tumors, brain trauma, endocrine and metabolic disturbances, nutritional disturbances, and medications. For example, infectious conditions which produce encephalitis may cause dementia of viral or bacterial origin. A relatively common example is herpetic encephalitis. Syphilis and acquired immune deficiency syndrome (AIDS), have been associated with dementia. Heavy metal toxicity, such as aluminum toxicity from dialysis, can cause dementia. A space-occupying brain lesion may produce dementia, such as brain metastases resulting from neoplasms. Brain trauma resulting in diffuse brain injury is a source of dementia. Thyroid disturbances, hyponatremia, and other endocrine disorders are known to cause dementia. Vitamin B (cobalamin) "# deficiency, which is associated with demyelination, is a cause of dementia, as is folate deficiency. Numerous medications can produce dementia or exacerbate a preexisting dementia. Some of the conditions which can produce dementia independently are now believed to be risk factors for AD as well. Examples of the latter include major depression and depression dysphoric disorder, and Vitamin B deficiency. "# See also: Alzheimer’s Disease: Behavioral and Social Aspects; Alzheimer’s Disease, Neural Basis of; Dementia, Semantic
Bibliography Adams F 1861 The Extant Works of Aretaeus, the Capadocian. Syndenham Society, London Ballard C, Grace J, McKeith I, Holmes C 1998 Neuroleptic sensitivity in dementia with Lewy bodies and Alzheimer’s disease. Lancet 351: 1032–3 Braak H, Braak E 1991 Neuropathological stageing of Alzheimer-related changes. Acta Neuropathologica 82: 239–59 Braak H, Braak E 1996 Development of Alzheimer-related neurofibrillary changes in the neocortex inversely recapitulates cortical myelogenesis. Acta Neuropathologica 92: 197–201 Brun A, Englund E, Gustafson L, Passant U, Mann D M A, Neary D, Snowden J S 1994 Clinical and neuropathological criteria for frontotemporal dementia. Journal Neuro Neurosurg Psychiatry 57: 416–8
3395
Dementia: Oeriew Buttini M, Orth M, Bellosta S, Akeefe H, Pitas R E, Wyss-Coray T, Mucke L, Mahley R W 1999 Expression of human apolipoprotein E3 or E4 in the brains of Apoe mice −/−: isoform-specific effects on neurodegeneration. Journal of Neuroscience 19: 4867–80 Esquirol J E D 1838 Des maladies mentales. Balliere, Paris Foster N L, Wilhelmsen K C, Sima A A F, Jones M Z, D’Amato C, Gilman S 1997 Frontotemporal dementia and Parkinsonism linked to chromosome 17: consensus conference. Ann Neurol 41: 706–15 Galen 1831–1833 De symptomatum differentis liber (Translation). In: Kuhn C G (ed.) Opera Omnia. Knobloch, Leipzig, Germany, Chap. VII pp. 200–1 Golomb J, Wisoff J, Miller D C, Boksay I, Kluger A, Weiner H, Salton J, Graves W 2000 Alzheimer’s disease comorbidity in normal pressure hydrocephalus: prevalence and shunt response. J Neurol Neurosurg Psychiatry 68: 778–81 Hachinski V C, Lassen N A, Marshall J 1974 Multi-infarct dementia: A cause of mental deterioration in the elderly. Lancet 2: 207–10 Henderson A S, Jorm A F 2000 Definition and epidemiology of dementia: A review. In: Maj M, Sartorius N (eds.) Dementia, WPA Series, Evidence and Experience in Psychiatry. Wiley, Chichester, UK, Vol. 3, pp. 1–33 Kertesz A 2000 Behavioral and psychological symptoms and frontotemporal dementia (Pick’s disease). International Psychogeriatrics 12(Suppl. 1): 183–7 McKeith I G, Galasko D, Kosaka K, Perry E K, Dickson D W, Hansen L A, Salmon D P, Lowe J, Mirra S S, Byrne E J, Lennox G, Quinn N P, Edwardson J A, Ince P G, Bergeron C, Burns A, Miller B L, Lovestone S, Collerton D, Jansen E N H, Ballard C, de Vos R A I, Wilcock G K, Jellinger K A, Perry R H 1996 Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB). Neurology 47: 1113–24 National Institute on Aging\Alzheimer’s Association Working Group 1996 Apolipoprotein E genotyping in Alzheimer’s disease. Lancet 347: 1091–5 Poirier J, Baccichet A, Dea D, Gauthier S 1993 Cholesterol synthesis and lipoprotein reuptake during synaptic remodelling in hippocampus in adult rats. Neuroscience 55: 81–90 Reisberg B, Ferris S H, de Leon M J, Crook T 1982. The global deterioration scale for assessment of primary degenerative dementia. American Journal of Psychiatry 139: 1136–9 Reisberg B, Pattschull-Furlan A, Franssen E, Sclan S G, Kluger A, Dingcong L, Ferris S H 1992 Dementia of the Alzheimer type recapitulates ontogeny inversely on specific ordinal and temporal parameters. In: Kostovic I, Knezevic S, Wisniewski H, Spilich G (eds.) Neurodeelopment, Aging, and Cognition. Birkhauser, Boston, MA, pp. 345–69 Reisberg B, Franssen E H, Hasan S M, Monteiro I, Boksay I, Souren L E M, Kenowsky S, Auer S R, Elahi S, Kluger A 1999 Retrogenesis: Clinical, physiologic and pathologic mechanisms in brain aging, Alzheimer’s and other dementing processes. European Archies of Psychiatry and Clinical Neuroscience 249(Suppl. 3): 28–36 Reisberg B, Franssen E, Shah M A, Weigel J, Bobinski M, Wisniewski H M 2000 Clinical diagnosis of dementia: A review. In: Maj M, Sartorius N (eds.) Dementia, WPA Series, Evidence and Experience in Psychiatry. Wiley, Chichester, UK, Vol. 3, pp. 69–115 Rush B 1973 An account of the state of mind and body in old age. In: Rush B, Medical Inquiries and Observations. Dobson, Philadelphia, PA, Vol. 2, pp. 311
Selkoe D J 1997 Alzheimer’s disease: Genotypes, phenotype and treatments. Science 275: 630–1 Tomlinson B E, Blessed G, Roth M 1970 Observations on the brains of demented old people. Journal of Neurological Science 11: 205–42 Xu J, Chen S, Ahmed S H, Chen H, Ku G, Goldberg M P, Hsu C Y 2001 Amyloid-β peptides are cytotoxic to oligodendrocytes. J Neurosci 21, RC118: 1–5
B. Reisberg Copyright # 2001 Elsevier Science Ltd. All rights reserved.
Dementia: Psychiatric Aspects Dementia has many aspects, and neurobiological, clinical, and family related or socioeconomic factors have been investigated. Here neuropsychiatric aspects are presented i.e., the signs and symptoms of dementia diseases which cause the disturbance in behavior, cognitive functions, and subjective experience of the patients, which are classified as emotional problems or personality change.
1. Definition of Dementia In history, the term dementia has been subject to several changes in meaning. Today, it is defined as acquired, severe loss of mental functions due to structural brain diseases. In dementia, the information processing capacity has deteriorated to a critical degree. Deficits are found predominantly in cognitive, but also in emotional and intentional domains. By definition, these deficits severely compromise the social and cultural activities of a person. There must be a loss of mental functions which had been acquired before (i.e., the long-standing cognitive deficiencies in mental retardation are excluded). The underlying pathology is a destruction or degeneration of brain structures, therefore dementia may not be caused by functional organic disorders such as psychoses or transient brain dysfunction like in delirium. Psychiatry is concerned primarily with the detection and diagnosis of dementia syndromes, and concerned secondly with the identification and treatment of certain dementia diseases. Dementia syndromes and dementia diseases have to be differentiated (Wells and Whitehouse 1996).
1.1 Dementia Syndromes Characteristic clinical profiles emerge, patterns of cognitive, affective, and intentional disturbances because in dementia diseases, the destruction or degen-
3396
International Encyclopedia of the Social & Behavioral Sciences
ISBN: 0-08-043076-7
D. S. Hamermesh
Dementia: Overview Dementia is a medical condition which is characterized by a generalized mental deterioration. The word has Latin roots, ‘de’ meaning separation, cessation or contraction, and ‘meme’ meaning ‘mind.’ Therefore, in dementia there is a cessation or contraction of the mind. The usage of the term dementia can be traced back to the Roman writer and encyclopedist, Aulus Cornelius Celsus in the first century AD. Celsus distinguished dementia, a chronic ‘contraction of the mind,’ from acute conditions such as delirium. The first medical identification of aging with dementia can be traced to Aretaeus of Cappadocia in the second century AD. He distinguished a condition which began in old age and continued until death, characterized by ‘a torpor of the senses, and a stupefaction of the gnostic and intellectual faculties’ (Adams 1861). Galen, perhaps the most influential physician of all time, also identified old age as a cause of dementia in the second century AD. He defined ‘morosis’ as a condition in which ‘the knowledge of letters and other acts are totally obliterated, indeed they can’t even remember their own names’ (Galen 1821–33 trans-
lation). One condition associated with morosis was old age. No further advances in the clinical description of dementia appear to have been made for more than 1500 years. In 1793, the eminent American physician, Benjamin Rush, a signer of the United States Declaration of Independence and author of the first American textbook of psychiatry, a man who is credited by the American Psychiatric Association with being the father of American psychiatry, added to the clinical description of dementia. He noted that: it would be sufficiently humbling to human nature if our bodies exhibited in old age the marks only of a second childhood, but human weakness descends even lower. I met with an instance of a woman between 80 and 90 who exhibited the marks of a second infancy, by such a total loss of her mental faculties as to lose all consciousness in discharging her alvine and urinary excretions. In this state of the body, a disposition to sleep succeeds the wakefulness of the first stages of old age’ (Rush 1793).
The accuracy of Benjamin Rush’s description has become increasingly apparent over the past two centuries. The modern term, ‘senile dementia,’ is derived from Esquirol (1838), who described this condition in a French textbook of psychiatry. He noted that this is a condition in which there occurs a weakening of the memory for recent experience and a loss of drive and will power. He noted that senile dementia (in French, deT mence senile), appears gradually and may be accompanied by emotional disturbances. In modern usage, the term dementia refers to either: (a) any condition associated with a generalized mental deterioration, or (b) a progressive generalized mental deterioration, frequently occurring in later life. Both usages are commonly applied.
1. Progressie Dementia The most important progressive dementia is Alzheimer’s disease, which plays a role in a majority of cases (Tomlinson et al. 1970). Other progressive dementias include cerebrovascular dementia, Lewy body dementia, and the frontotemporal dementias. With the exception of the frontotemporal dementias, these conditions increase in occurrence with increasing age. Consequently, the modern increase in lifespan in most regions throughout the world has been accompanied by a dramatic increase in the occurrence of these conditions (Henderson and Jorm 2000).
1.1 Alzheimer’s Disease Alzheimer’s disease (AD) is one of the most devastating medical conditions of contemporary times. 3389
Dementia: Oeriew Table I Global Deterioration Scale (GDS) for age-associated cognitive decline and Alzheimer’s disease1 GDS stage 1 2
3
4
5
3390
Clinical characteristics No Subjective complaints of memory deficit. No memory deficit evident on clinical interview. Subjective complaints of memory deficit, most frequently in following areas: (a) Forgetting where one has placed familiar objects; (b) Forgetting names one formerly knew well. No objective evidence of memory deficit on clinical interview. No objective deficit in employment or social situations. Appropriate concern with respect to symptomatology. Earliest clear-cut deficits. Manifestations in more than one of the following areas: (a) Patient may have gotten lost when traveling to an unfamiliar location. (b) Co-workers become aware of patient’s relatively poor performance. (c) Word and/or name finding deficit become evident to intimates. (d) Patient may read a passage or book and retain relatively little material. (e) Patient may demonstrate decreased facility remembering names upon introduction to new people. (f) Patient may have lost or misplaced an object of value. (g) Concentration deficit may be evident on clinical testing. Objective evidence of memory deficit obtained only with an intensive interview. Decreased performance in demanding employment and social settings. Denial begins to become manifest in patient. Mild to moderate anxiety frequently accompanies symptoms. Clear-cut deficit on careful clinical interview. Deficit manifest in following areas: a Decreased knowledge of current and recent events. b May exhibit some deficits in memory of one’s personal history. c Concentration deficit elicited on serial subtractions. d Decreased ability to travel, handle finances, etc. Frequently no deficit in following areas: (a) Orientation to time and place. (b) Recognition of familiar persons and faces. (c) Ability to travel to familiar locations. Inability to perform complex tasks. Denial is dominant defense mechanism. Flattening of affect and withdrawal from challenging situations. Patient can no longer survive without some assistance. Patient is unable during interview to recall a major relevant aspect of their current life, e.g.: a Their address or telephone number of many years. b The names of close members of their family (such as grandchildren). c The name of the high school or college from which they graduated.
Diagnosis and prognosis2,3 Normal Adult Age associated memory impaired (sometimes termed normal aged forgetfulness or aged-associated cognitive decline) 15% develop dementia within 4 years2 Mild cognitive impairment Two-thirds develop dementia within 4 years2
Mild Alzheimer’s disease Mean duration: 2 years
Moderate Alzheimer’s disease Mean duration: 1.5 years
Dementia: Oeriew Table I Continued GDS stage
6
7
Clinical characteristics
Diagnosis and prognosis2,3
Frequently some disorientation to time (date, day of the week, season, etc.) or to place. An educated person may have difficulty counting back from 40 by 4s or from 20 by 2s. Persons at this stage retain knowledge of many major facts regarding themselves and others. They invariably know their own names and generally know their spouse’s and children’s names. They require no assistance with toileting or eating, but may have difficulty choosing the proper clothing to wear. May occasionally forget the name of the spouse upon whom Moderately severe Alzheimer’s disease they are entirely dependent for survival. Mean duration: 2.5 years Will be largely unaware of all recent events and experiences in their lives. Retain some knowledge of their surroundings; the year, the season, etc. May have difficulty counting by 1s from 10, both backward and sometimes forward. Will require some assistance with activities of daily living: (a) May become incontinent. (b) Will require travel assistance but occasionally will be able to travel to familiar locations. Diurnal rhythm frequently disturbed. Almost always recall their own name. Frequently continue to be able to distinguish familiar from unfamiliar persons in their environment. Personality and emotional changes occur. These are quite variable and include: a delusional behavior, e.g., patients may accuse their spouse of being an imposter; may talk to imaginary figures in the environment, or to their own reflection in the mirror. b obsessive symptoms, e.g., person may continually repeat simple cleaning activities. c anxiety symptoms, agitation, and even previously non-existent violent behavior may occur. d cognitive abulia, e.g., loss of willpower because an individual cannot carry a thought long enough to determine a purposeful course of action. All verbal abilities are lost over the course of this stage. Severe Alzheimer’s disease Early in this stage words and phrases are spoken but speech is Mean time to demise: 2–3 years very circumscribed. Potential for survival: 7 or Later there is no speech at all—only unintelligible vocalizations. more years Incontinent; requires assistance toileting and feeding. Basic psychomotor skills (e.g., ability to walk) are lost with the progression of this stage. The brain appears no longer to be able to tell the body what to do. Generalized and cortical neurologic signs and symptoms are frequently present.
1. Reisberg B, Ferris S H., de Leon M J, & Crook T. 1982 The global deterioration scale for assessment of primary degenerative dementia. American Journal of Psychiatry 139: 1136–1139. Copyright 1983 by Barry Reisberg, M.D. 2. Kluger A, Ferris S H, Golomb J, Mittelman, M S, Reisberg B 1999 Neuropsychological prediction of decline to dementia in nondemented elderly. Journal of Geriatric Psychiatry and Neurology 12: 168–79. 3. Reisberg B, Franssen E, Shah M A, Weigel J, Bobinski M, Wisniewski H M 2000 Clinical diagnosis of dementia: A review. In: Maj M, Sartorius N (eds.) Dementia, WPA Series, Evidence and Experience in Psychiatry, Wiley, Chichester, UK, Vol. 3, pp. 69–115.
3391
Dementia: Oeriew For example, in the United States, the number of persons in nursing homes and related institutions with AD exceeds the total number of persons in all hospitals and related institutions. Consequently, the institutional burden of AD in the United States is approximately the same as the institutional burden of all other illnesses combined. Worldwide, AD is estimated to afflict more than 15 million persons, and the prevalence continues to increase with increasing life expectancy of the world’s people. The precise mechanism of the cause of AD is unknown. However, particular genotypes which predispose to early onset AD have been identified. These genetic ‘defects’ are β-amyloid precursor protein mutations located on chromosome 21, presenilin 1 mutations located on chromosome 14, and presenilin 2 mutations which are located on chromosome 1. Some investigators point out that each of these mutations is associated with increased production of β-amyloid protein, one of the neuropathologic hallmarks of AD (Selkoe 1997). However, the presenilin mutations in particular, have been related to a variety of other pathologies apart from increased β-amyloid protein. Further evidence for the role of β-amyloid in the etiopathogenesis of AD is the observation that persons with Down’s syndrome develop Alzheimer’s pathology early in life and carry an extra copy of the βamyloid precursor protein gene resulting in excess βamyloid production. The occurrence of the common late-life form of AD has also been associated with particular genotypes. The most clearly identified gene which influences the occurrence of late life, also known as ‘sporadic’ Alzheimer’s disease, is the apolipoprotein E (apoE) gene (National Institute on Aging \Alzheimer’s Association Working Group 1996). Caucasians who carry the apoE4 allele are at increased risk for AD in later life. Caucasians who are homogenous for apoE4 have as much as eight times the risk of AD as similarly aged persons who do not carry the apoE4 allele. Other genes and gene interactions which influence the occurrence of the common, late-life form of AD have not yet been fully elucidated. Although the mechanism by which AD occurs is not known, a characteristic clinical course of AD has been described (Reisberg et al. 1982, 2000). This characteristic clinical course is accompanied by characteristic neuropathologic manifestations and a characteristic neuropathologic progression. Clinically, AD can be described on a continuum with the changes in what is now termed normal aging, progressing to mild cognitive impairment (MCI) and subsequently to AD. This clinical continuum is illustrated in terms of the cognitive, functional and emotional progression of aging and AD in Table 1. Functionally, the progression of brain aging, MCI and AD can be described in even greater detail, in terms which are universally clear to both lay persons and professionals. This characteristic functional progres3392
sion is familiar to many observers because it reverses the sequence of functional acquisition in human development, a phenomenon which has been termed ‘retrogenesis’ (Table 2) (Reisberg et al. 1999, 2000) The hallmark neuropathologic manifestations of AD are extracellular senile plaques which contain the β-amyloid protein, and intracellular neurofibrillary tangles which contain the protein tau (see Alzheimer’s Disease, Neural Basis of ). Very strong relationships have been found between the clinical progression of AD and the progression of pathology in the hippocampus, a brain region which has been notably associated with memory. Progressive pathologic manifestations in the hippocampus include neurofibrillary pathology, volume loss, and neuronal cellular loss. Although the hippocampus is a brain region which manifests early and progressive AD pathology, AD is a generalized brain disease with, for example, progressive decrements in brain glucose utilization (energy metabolism) and progressive slowing of brain wave electrical activity on the electroencephalogram, as well as neuropathologic manifestations in numerous brain regions, which become particularly evident as AD progresses. Neuropathologic stages of AD have been described (Braak and Braak 1991). These are transentorhinal stages I and II, limbic stages III and IV, and neocortical stages V and VI. Each of these stages of Braak and Braak are based upon the evolution and spread of neurofibrillary pathology in the brain of the AD patient. Braak and Braak (1996) and Reisberg et al. (1992, 1999) have described a common basis for the neuropathologic and clinical manifestations of AD. This is the progressive involvement of the most recently, and therefore the most thinly, myelinated brain regions, followed by progressively more thickly myelinated, and therefore, better protected, brain regions. The most thickly myelinated brain regions subsume the functions and associated cognitive skills, which are the first to be acquired in the course of human development. Conversely, the most thinly myelinated brain regions subsume the most recently acquired functions and associated cognition. These recently myelinated regions are the most vulnerable to AD pathology. Consequently, cognitive and functional skills which are the most recently acquired are the most vulnerable to AD pathology, and those cognitive and functional skills which are the first to be acquired in normal human development are the last to be lost with the progression of AD. In brief, last in, first out. This retrogenesis phenomenon, which is illustrated for functional skills in Table 2, also applies to cognition and many aspects of brain physiology, including neurologic reflexes and apparently, to at least some extent, brain electrophysiology and metabolism. Very recently it has been demonstrated that the β-amyloid, the major putative toxic pathology in AD is destructive to the oligodendroglia, the brain cells
Table 2 Retrogenesis: functional landmarks in normal human development and Alzheimer’s disease (AD) Normal Development Approximate Total Duration: 20 years Approximate age Adolescence 13–19 years Late childhood 8–12 years Middle childhood 5–7 years Early childhood 5 years 4 years 4 years 3–4.5 years 2–3 years Infancy 15 months 1 year 1 year 6–10 months 2–4 months 1–3 months
Approximate duration in development
Acquired abilities
Alzheimer’s Degeneration Approximate Total Duration: 20 years
Lost abilities
Alzheimer stage
Approximate duration in AD
Developmental age of AD
7 years
Hold a job
Hold a job
3 – Incipient
7 years
19–13 years: Adolescence
5 years
Handle simple finances
Handle simple finances
4 – Mild
2 years
12–8 years: Late childhood
2.5 years
Select proper clothing
Select proper clothing
5 – Moderate
1.5 years
7–5 years: Middle childhood
4 years
Put on clothes unaided
Put on clothes unaided
2 years
5–2 years: Early childhood
Shower unaided Toilet unaided Control urine Control bowels
Shower unaided Toilet unaided Control urine Control bowels
6a – Moderately severe b c d e
Speak 5–6 words
Speak 5–6 words
7a – Severe
7 years or longer
15 months to birth: Infancy
Speak 1 word Walk Sit up Smile Hold up head
Speak 1 word Walk Sit up Smile Hold up head
b c d e f
1.5 years
Copyright # 1984, 1986, 1996, 2000 by Barry Reisberg, M.D. All rights reserved.
3393
Dementia: Oeriew which produce the myelin (Xu et al. 2001). ApoE, the AD risk-determining factor, is a molecule associated with cholesterol transport. ApoE has been shown to affect neuronal repair mechanisms and the apoE3 allele appears to have a greater neuroprotective effect than the apoE4 allele (Poirier et al. 1993; Buttini et al. 1999). Therefore, a common basis for the molecular, pathologic, and clinical manifestations of AD can be postulated although many elements of the precise pathogenic mechanism remain unknown.
1.2 Vascular Dementia Formerly, this entity was designated multi-infarct dementia because of its strong relationship to strokes, both large and small (Hachinski et al. 1974). Although originally considered by Hachinski to be a stroke-like entity with an abrupt onset and stepwise pattern of deterioration, this deterioration pattern is rarely observed. Vascular dementia is now thought to be a condition marked by progressive decline in cognition and functioning in which cerebrovascular, i.e., stroke risk factors, play a major role. These risk factors include hypertension and cardiovascular disease, as well as more overt evidence of cerebrovascular disease such as transientischemic attacks and focal neurologic signs and symptoms. In most cases, vascular dementia occurs in association with Alzheimer’s brain pathology, a condition which is sometimes termed ‘mixed dementia.’ Much less frequently, vascular dementia appears to occur without evidence of concurrent AD. Consequently, many investigators view vascular dementia as on a continuum with AD. This continuum concept has become particularly compelling in recent years, since virtually all of the elements associated with vascular dementia have been shown to be risk factors for so-called ‘pure AD.’ In accordance with the concept of an additive morbidity of vascular dementia and AD, the course of vascular dementia has been found to be generally more rapid than AD. Vascular dementia is generally considered to be the most common dementia entity after AD.
1.3 Lewy Body Dementia Lewy bodies are spherical inclusions located in the cytoplasm of neurons which characteristically contain a protein known as α-synuclein. Originally Lewy bodies were considered to be a prominent feature of Parkinson’s disease and were not associated with late life dementia. However, new staining techniques in the 1990s indicated that Lewy bodies in the brain stem and the cortex commonly occur in dementia patients studied postmortem. Estimates indicate that as many 3394
as 15 to 25 percent of dementia patients manifest Lewy bodies at the time of demise (McKeith et al. 1996). However, in the great majority of these cases, Lewy bodies exist together with neuropathologic manifestations of AD and\or vascular dementia. When this mixed neuropathology occurs, the clinical manifestations of the dementia are those of AD and\or vascular dementia, and there is no distinctive Lewy body dementia clinical syndrome. In approximately 4 percent of all dementia cases coming to autopsy, Lewy bodies occur in the brain in the absence of other dementia disorders. In these cases, a classical Lewy body dementia (LBD) clinical syndrome occurs. This syndrome is marked by three core features, any\or all of which may be present: (a) a relatively fluctuating clinical course, with variability in cognition; (b) the presence of vivid, well formed, visual hallucinations; and (c) the presence of Parkinsonian features. Another important aspect of LBD is sensitivity to neuroleptic (antipsychotic) medications, particularly those known to be associated with Parkinsonian side effects (Ballard et al. 1998). In general, the onset of LBD is more acute than the onset of AD, and the course of LBD appears to be shorter than that of AD.
1.4 Frontotemporal Dementias These are a diverse group of disorders for which various classification schemata have been developed. For example, biomolecular categorizations have been developed recently which are extremely useful in categorizing one subgroup of frontotemporal dementias, those with frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17) (Foster et al. 1997). The FTDP-17 dementias are characterized by mutations which alter tau, the protein responsible for neurofibrillary changes such as those found in AD. Another frontotemporal dementia type marked by abnormal tau accumulation is Pick’s disease. In Pick’s disease there is an intracellular inclusion known as the Pick body which contains tau accumulations as well as other substances. Other forms of frontotemporal dementia are classified mainly on the basis of their clinical presentation. They include semantic dementia (see Dementia, Semantic), progressive aphasia, and motor neuron disease dementia. The core clinical features of the frontotemporal dementias have been described in part as disinhibition, decreased insight, apathy, disorganization, lack of personal hygiene, mental rigidity, and hyperorality (Brun et al. 1994, Kertesz 2000). In addition, aphasia and other language disturbances are frequently present. Like the basic pathologic disturbances, these behavioral manifestations are very heterogenous and occur on a clinical spectrum. In general, the frontotemporal dementias occur in adults at a younger age than AD. Some believe that
Dementia: Oeriew these conditions are very common in patients who are institutionalized for mental illness.
1.5 Other Progressie Dementias Various other diverse conditions produce progressive dementia. In general, these other conditions are believed to be considerably less common than the dementias which have been reviewed more specifically in the preceding sections. Perhaps the most notable of these other dementias are the prion dementias, of which the most frequent is Creutzfeldt-Jakob disease (CJD). Prion dementias are believed to result from a self-propagating conformational change in a protein, known as the prion protein. This prion, a proteinaceous infective agent, can be acquired either spontaneously or through transmission of biologic materials containing the prion, including brain, pituitary glandular substance, and corneal lens transplants. Spontaneous CJD occurs in approximately one person per million population worldwide. Recently, a form of transmissible CJD arose in Britain as a result of transmission of a prion disease in cattle to humans. This ‘epidemic’ which has affected dozens of persons in Britain and, more recently, several persons on the European continent, has resulted in the destruction of the entire British cattle herd and a change in dietary habits of tens of millions of persons in Europe and elsewhere. Consequently, although the prion dementias remain rare conditions in humans, the threat of the spread of these proteinaceous infections, has caused somewhat justified alarm, in particular in Europe, but also throughout the world. Other relatively uncommon progressive dementias include progressive supranuclear palsy, and corticobasilar degeneration. These conditions, like some of the frontotemporal dementias, are marked by abnormal tau protein and resultant neurofibrillary accumulations. There are also many progressive dementias associated with broader pathologic spectra, of which dementia is only one element. Among these are the dementia of Down’s syndrome, the dementia of normal pressure hydrocephalus (NPH), and the dementia of Huntington’s disease. Some of these dementias are very closely related to AD dementia. For example, persons with Down’s syndrome universally develop an Alzheimer’s type neuropathologic and clinical picture at a relatively early age in comparison with persons with classical AD. Similarly, brain biopsy studies have recently demonstrated that many elderly persons with NPH who manifest a dementia component to the clinical syndrome, show Alzheimer’stype pathology, specifically neuritic plaques, upon brain tissue examination (Golomb et al. 2000). As is the case for AD, the percentage of NPH dementia patients with biopsies demonstrating neuritic plaques
increases with dementia severity, rising from about 20 percent of patients with MCI to about 75 percent of patients in stage 6 and 7 of the global deterioration scale (see Table 1). These studies indicate that the gait disturbance which is characteristic of NPH appears to be associated with dilated cerebral ventricles (i.e., expansion of the fluid filled cavities in the brain), whereas the dementia component of NPH is probably related to concomitant AD.
2. Dementias with Variable Prognoses Numerous diverse physiologic disturbances can produce dementias which may be acute or chronic, reversible or permanent. These diverse conditions include infectious conditions, toxins, tumors, brain trauma, endocrine and metabolic disturbances, nutritional disturbances, and medications. For example, infectious conditions which produce encephalitis may cause dementia of viral or bacterial origin. A relatively common example is herpetic encephalitis. Syphilis and acquired immune deficiency syndrome (AIDS), have been associated with dementia. Heavy metal toxicity, such as aluminum toxicity from dialysis, can cause dementia. A space-occupying brain lesion may produce dementia, such as brain metastases resulting from neoplasms. Brain trauma resulting in diffuse brain injury is a source of dementia. Thyroid disturbances, hyponatremia, and other endocrine disorders are known to cause dementia. Vitamin B (cobalamin) "# deficiency, which is associated with demyelination, is a cause of dementia, as is folate deficiency. Numerous medications can produce dementia or exacerbate a preexisting dementia. Some of the conditions which can produce dementia independently are now believed to be risk factors for AD as well. Examples of the latter include major depression and depression dysphoric disorder, and Vitamin B deficiency. "# See also: Alzheimer’s Disease: Behavioral and Social Aspects; Alzheimer’s Disease, Neural Basis of; Dementia, Semantic
Bibliography Adams F 1861 The Extant Works of Aretaeus, the Capadocian. Syndenham Society, London Ballard C, Grace J, McKeith I, Holmes C 1998 Neuroleptic sensitivity in dementia with Lewy bodies and Alzheimer’s disease. Lancet 351: 1032–3 Braak H, Braak E 1991 Neuropathological stageing of Alzheimer-related changes. Acta Neuropathologica 82: 239–59 Braak H, Braak E 1996 Development of Alzheimer-related neurofibrillary changes in the neocortex inversely recapitulates cortical myelogenesis. Acta Neuropathologica 92: 197–201 Brun A, Englund E, Gustafson L, Passant U, Mann D M A, Neary D, Snowden J S 1994 Clinical and neuropathological criteria for frontotemporal dementia. Journal Neuro Neurosurg Psychiatry 57: 416–8
3395
Dementia: Oeriew Buttini M, Orth M, Bellosta S, Akeefe H, Pitas R E, Wyss-Coray T, Mucke L, Mahley R W 1999 Expression of human apolipoprotein E3 or E4 in the brains of Apoe mice −/−: isoform-specific effects on neurodegeneration. Journal of Neuroscience 19: 4867–80 Esquirol J E D 1838 Des maladies mentales. Balliere, Paris Foster N L, Wilhelmsen K C, Sima A A F, Jones M Z, D’Amato C, Gilman S 1997 Frontotemporal dementia and Parkinsonism linked to chromosome 17: consensus conference. Ann Neurol 41: 706–15 Galen 1831–1833 De symptomatum differentis liber (Translation). In: Kuhn C G (ed.) Opera Omnia. Knobloch, Leipzig, Germany, Chap. VII pp. 200–1 Golomb J, Wisoff J, Miller D C, Boksay I, Kluger A, Weiner H, Salton J, Graves W 2000 Alzheimer’s disease comorbidity in normal pressure hydrocephalus: prevalence and shunt response. J Neurol Neurosurg Psychiatry 68: 778–81 Hachinski V C, Lassen N A, Marshall J 1974 Multi-infarct dementia: A cause of mental deterioration in the elderly. Lancet 2: 207–10 Henderson A S, Jorm A F 2000 Definition and epidemiology of dementia: A review. In: Maj M, Sartorius N (eds.) Dementia, WPA Series, Evidence and Experience in Psychiatry. Wiley, Chichester, UK, Vol. 3, pp. 1–33 Kertesz A 2000 Behavioral and psychological symptoms and frontotemporal dementia (Pick’s disease). International Psychogeriatrics 12(Suppl. 1): 183–7 McKeith I G, Galasko D, Kosaka K, Perry E K, Dickson D W, Hansen L A, Salmon D P, Lowe J, Mirra S S, Byrne E J, Lennox G, Quinn N P, Edwardson J A, Ince P G, Bergeron C, Burns A, Miller B L, Lovestone S, Collerton D, Jansen E N H, Ballard C, de Vos R A I, Wilcock G K, Jellinger K A, Perry R H 1996 Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB). Neurology 47: 1113–24 National Institute on Aging\Alzheimer’s Association Working Group 1996 Apolipoprotein E genotyping in Alzheimer’s disease. Lancet 347: 1091–5 Poirier J, Baccichet A, Dea D, Gauthier S 1993 Cholesterol synthesis and lipoprotein reuptake during synaptic remodelling in hippocampus in adult rats. Neuroscience 55: 81–90 Reisberg B, Ferris S H, de Leon M J, Crook T 1982. The global deterioration scale for assessment of primary degenerative dementia. American Journal of Psychiatry 139: 1136–9 Reisberg B, Pattschull-Furlan A, Franssen E, Sclan S G, Kluger A, Dingcong L, Ferris S H 1992 Dementia of the Alzheimer type recapitulates ontogeny inversely on specific ordinal and temporal parameters. In: Kostovic I, Knezevic S, Wisniewski H, Spilich G (eds.) Neurodeelopment, Aging, and Cognition. Birkhauser, Boston, MA, pp. 345–69 Reisberg B, Franssen E H, Hasan S M, Monteiro I, Boksay I, Souren L E M, Kenowsky S, Auer S R, Elahi S, Kluger A 1999 Retrogenesis: Clinical, physiologic and pathologic mechanisms in brain aging, Alzheimer’s and other dementing processes. European Archies of Psychiatry and Clinical Neuroscience 249(Suppl. 3): 28–36 Reisberg B, Franssen E, Shah M A, Weigel J, Bobinski M, Wisniewski H M 2000 Clinical diagnosis of dementia: A review. In: Maj M, Sartorius N (eds.) Dementia, WPA Series, Evidence and Experience in Psychiatry. Wiley, Chichester, UK, Vol. 3, pp. 69–115 Rush B 1973 An account of the state of mind and body in old age. In: Rush B, Medical Inquiries and Observations. Dobson, Philadelphia, PA, Vol. 2, pp. 311
Selkoe D J 1997 Alzheimer’s disease: Genotypes, phenotype and treatments. Science 275: 630–1 Tomlinson B E, Blessed G, Roth M 1970 Observations on the brains of demented old people. Journal of Neurological Science 11: 205–42 Xu J, Chen S, Ahmed S H, Chen H, Ku G, Goldberg M P, Hsu C Y 2001 Amyloid-β peptides are cytotoxic to oligodendrocytes. J Neurosci 21, RC118: 1–5
B. Reisberg Copyright # 2001 Elsevier Science Ltd. All rights reserved.
Dementia: Psychiatric Aspects Dementia has many aspects, and neurobiological, clinical, and family related or socioeconomic factors have been investigated. Here neuropsychiatric aspects are presented i.e., the signs and symptoms of dementia diseases which cause the disturbance in behavior, cognitive functions, and subjective experience of the patients, which are classified as emotional problems or personality change.
1. Definition of Dementia In history, the term dementia has been subject to several changes in meaning. Today, it is defined as acquired, severe loss of mental functions due to structural brain diseases. In dementia, the information processing capacity has deteriorated to a critical degree. Deficits are found predominantly in cognitive, but also in emotional and intentional domains. By definition, these deficits severely compromise the social and cultural activities of a person. There must be a loss of mental functions which had been acquired before (i.e., the long-standing cognitive deficiencies in mental retardation are excluded). The underlying pathology is a destruction or degeneration of brain structures, therefore dementia may not be caused by functional organic disorders such as psychoses or transient brain dysfunction like in delirium. Psychiatry is concerned primarily with the detection and diagnosis of dementia syndromes, and concerned secondly with the identification and treatment of certain dementia diseases. Dementia syndromes and dementia diseases have to be differentiated (Wells and Whitehouse 1996).
1.1 Dementia Syndromes Characteristic clinical profiles emerge, patterns of cognitive, affective, and intentional disturbances because in dementia diseases, the destruction or degen-
3396
International Encyclopedia of the Social & Behavioral Sciences
ISBN: 0-08-043076-7