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Drugs to preserve brain function in Alzheimer's patients may only be effective in patients with severe dementia. One of the hallmalks of Alzheimer's disease is the loss of a type of nerve cell called cholinergic nerve cells. These cells use acetylcholine as a neurotransmitter. Researchers measured acetylcholine activity in the autopsy brain samples of 66 elderly nursing home patients who had died. Only those with severe dementia while alive had decreased acetylcholine activity. Those with no, mild, or moderate, dementia had normal acetylcholine activity.

Context: Lewy bodies (LBs) are intraneuronal inclusions in the brain that have been increasingly recognized as neuropathological lesions with relevance not only to Parkinson disease but also to Alzheimer disease. However, the degree to which the density of LBs in the brain contributes to the severity of dementia has not been clear. Objective: To determine the degree to which LB "burden" contributes to dementia. Design: Brain specimens were examined from 273 consecutive autopsies of elderly subjects residing in a nursing home. The numbers and densities of LBs were determined in multiple brain regions, and their correlation with a measure of cognition and functional status (Clinical Dementia Rating) during the 6 months preceding death was determined. Setting and Patients: Postmortem study of nursing home residents. Results: The severity of dementia correlated significantly and positively with the density of LBs. These correlations were independent of other neuropathological disorders commonly associated with dementia, including Alzheimer disease. The density of LBs correlated significantly with dementia severity whether or not the diagnostic criteria for Alzheimer disease were met and after the contribution of classical Alzheimer disease lesions, neuritic plaques, and neurofibrillary tangles had been accounted for by partial correlation analysis. Conclusion: Lewy body inclusions appear to contribute significantly to cognitive deficits in the elderly in a manner that is independent of other neuropathological disorders. [ABSTRACT FROM AUTHOR]

Background: The relationship between neuropathological lesions and mild, "preclinical," cognitive impairments of Alzheimer disease is poorly understood. Identification of the lesions that are most closely associated with the earliest symptoms of Alzheimer disease is crucial to the understanding of the disease process and the development of treatment strategies to affect its progression. Design and Main Outcome Measures: We examined the extent of neurofibrillary tangles (NFTs) in 4 neocortical regions, the hippocampus, the entorhinal cortex, and the amygdala in 65 elderly subjects with no dementia, questionable dementia, mild dementia, or moderate dementia as assessed using the Clinical Dementia Rating Scale (CDR). Setting and Patients: Postmortem study of nursing home residents. Results: Neurofibrillary tangles were present in the entorhinal cortex and the hippocampus of all subjects, including those without cognitive deficits. Neocortical NFTs were mostly absent in the nondemented (CDR score, 0.0) subjects. The density of NFTs in the questionably demented (CDR score, 0.5) subjects was not significantly increased (P>.20) relative to the nondemented group in any of the brain regions studied. Significant increases (P<.04) in NFT density become apparent first in the amygdala and the temporal cortex in subjects rated to be mildly impaired (CDR score, 1.0). By the time that cognitive impairments were judged to be moderately severe (CDR score, 2.0), all regions of the brain examined, except for the occipital cortex, were significantly (P<.05) involved. Conclusions: Some NFTs are present in the entorhinal cortex and hippocampus of most elderly individuals irrespective of their cognitive status, but the density of NFTs increases as a function of dementia severity. [ABSTRACT FROM AUTHOR]

Background: Identification of the neuropathological lesions that are most closely associated with the earliest symptoms of Alzheimer disease (AD) is crucial to the understanding of the disease process and the development of treatment strategies to affect its progress. Do the classical neuropathological lesions of AD precede, follow, or occur in synchrony with the earliest signs of cognitive deterioration? Design and Outcome Measures: We examined the extent of neuritic plaque (NP) formation in 5 neocortical regions and the hippocampus, entorhinal cortex, and amygdala in 66 elderly subjects with no dementia, questionable dementia, or mild dementia as assessed using the Clinical Dementia Rating Scale (CDR). Setting and Patients: Postmortem study of nursing home residents. Results: Even questionable dementia (CDR, 0.5) was associated with a significant (P=.04) increase in neocortical NP density. The density of NPs increased further with increasing dementia severity in all brain regions examined. However, subjects with questionable dementia or definite but mild dementia did not differ significantly from each other. Density of NPs was nearly maximal in subjects with moderate dementia (CDR=2.0), suggesting that other neuropathological changes may be responsible for cognitive deficits beyond this level. Dementia severity correlated significantly with the density of NPs in all brain regions examined (r range, 0.47-0.56; P <.001), even when subjects with a CDR of 0 were excluded. Conclusions: These findings are consistent with the hypothesis that NPs are among the earliest neuropathological lesions in AD. Even very mild or questionable dementia is associated with increased density of neocortical NPs that do not distinguish between clinically questionable vs definite dementia. [ABSTRACT FROM AUTHOR]