Mohammed T. Abou-Saleh

Principles and Practice of Geriatric Psychiatry.Editors: Professor John R. M. Copeland, Dr Mohammed T. Abou-Saleh and Professor Dan G. BlazerCopyright & 2002 John Wiley & Sons LtdPrint ISBN 0-471-98197-4 Online ISBN 0-470-84641-049Neuropathology: Other DementiasJ. M. MacKenzieGrampian University Hospitals NHS Trust, Aberdeen, UKThere are many causes of dementia in addition to Alzheimer’sdisease (AD) and vascular dementia, and the commonest ofthese seems to be dementia with Lewy bodies (DLB), whichperhaps accounts for 10% of all cases of dementia, althoughthe precise incidence depends on the population studied and thepathological criteria used for diagnosis 1,2 . In a hospital series, itmay be second only to AD as a cause of dementia 3 . AfterDLB, other causes are distinctly rare and include Creutzfeldt–Jakob disease, Huntington’s disease and the frontotemporaldementias.DEMENTIA IN PARKINSON’S DISEASE ANDDEMENTIA WITH LEWY BODIESParkinson’s disease is a disorder characterized by rigidity, tremorand bradykinesia, usually with an onset in the sixth decade.Neuronal loss and gliosis are typically evident in the substantianigra and loci coerulei, but also in the dorsal vagal nuclei, dorsalraphe nuclei and nucleus basalis of Meynert. Lewy bodies,spherical intracytoplasmic inclusions composed of granular andfilamentous elements, immunoreactive with antibodies againstneurofilament protein, paired helical filaments, ubiquitin and, inaminergic neurones, tyrosine hydroxylase protein 4–7 , are foundnot only in pigmented brainstem neurones but also in over 20different nuclei, pigmented and non-pigmented 8 . Changes inaminergic pathways, particularly dopaminergic, are well documented4 .Dementia has been reported to affect 34.6% of patients withparkinsonism in one large autopsy series and it seems likely that anumber of different mechanisms are responsible 9 .Concurrent ADIt has been claimed that AD is six times more common in patientswith Parkinson’s disease than in age-matched controls 10 and 12–25% of demented parkinsonian patients in one series had AD 4 .In Jellinger’s study 9 , most of the demented parkinsonians alsohad the pathological changes of AD. Other studies have shownthat cortical senile plaques and neurofibrillary tangles are morenumerous in demented patients with Parkinson’s disease thannon-demented Parkinson’s disease sufferers or controls 11–13 . Thewide spectrum of dementia in Parkinson’s disease has beenattributed to the overlap of clinical and subclinical pathologicalchanges in both diseases 14 .Innominato-cortical DysfunctionNeuronal loss from the basal nucleus of Meynert (BNM) isgreater in demented than in non-demented parkinsonianpatients 11 and this depletion may be 40–80% in the former asopposed to 20–50% in the latter 15,16 .Furthermore, there is also evidence of an accompanyingreduction in choline acetyltransferase (CAT) and acetylcholinesterasein the BNM and all areas of the cerebral cortex. DecreasedCAT activity in the temporal cortex correlates with BNMneuronal loss in Parkinson’s disease, unlike AD, and alsocorrelates with memory impairment, although not with thenumbers of cortical plaques and tangles 17 .Neuronal Loss in Pigmented Brainstem NucleiIt is generally stated that there is no correlation between neuronalloss in the substantia nigra and mental impairment 11 , but it hasbeen found that neuronal loss in the medial substantia nigracorrelates with the severity of dementia, presumably due to loss ofprojections to the caudate nuclei, limbic system and cerebralcortex 18 . In addition, severe neuronal loss and subnormalnoradrenaline metabolism in the loci coerulei are commoner indemented than non-demented parkinsonian patients 11,19 . Medialsubstantia nigra loss, together with cortical AD changes, seemedto underlie dementia in one study, whereas depression inParkinson’s disease was associated with more severe loss ofneurones from the dorsal raphe nuclei 13 .Dementia with Lewy BodiesSmall numbers of Lewy bodies may be present in the cerebralcortex in patients without neurological impairment, or withParkinson’s disease. However, a disorder characterized byearly neuropsychiatric features, dementia, visual hallucinations,fluctuating conscious level and relatively mild Parkinson’sdisease justifies separate identification as DLB 20 because ofdifferent therapeutic implications. Many cases also have largenumbers of brainstem Lewy bodies and it seems likely thatDLB, with a predominantly cortical distribution of Lewybodies, lies at one end of a spectrum of Lewy bodydisorders, in which idiopathic Parkinson’s disease, withLewy bodies predominantly localized in the brainstem, isthe opposite end 21 .In many reported cases, cortical Lewy bodies have beenassociated with AD-type changes, leading to the conclusion thatPrinciples and Practice of Geriatric Psychiatry, 2nd edn. Edited by J. R. M. Copeland, M. T. Abou-Saleh and D. G. Blazer&2002 John Wiley & Sons, Ltd