A quantitative histological study of early clinical and preclinical Alzheimer's disease

Abstract

Brains from 70 unselected general hospital necropsy cases aged 60-95 years were surveyed histologically for changes of Alzheimer's disease using Congo Red-Gallocyanin preparations. Counts were made of neurofibrillary tangles in two areas of the neocortex, the hippocampal formation and the substantia innominata. Neurons were counted in the subiculum of the hippocampus, the substantia innominata and the locus coeruleus. In addition, a retrospective enquiry was made concerning the mental health of the patients in the study; cognitive performance was graded on the Global Deterioration Scale (GDS 1-7). Four cases (5.7%) had clinical and pathological changes amounting to early Alzheimer's disease. Tangles were very numerous in all areas and there was a 30% deficit or more of neurons in at least two of the structures counted. Although the diagnosis of Alzheimer's disease was not recorded during life, all had shown signs of early cognitive decline (GDS grades 3-6). A further six cases (8.6%) showed excessive tangle accumulation which may represent preclinical Alzheimer's disease. Tangles were present in the temporal neocortex (Brodmann area 22), whereas they were absent in the remainder of the survey. Tangle density in the hippocampal formation (greater than 50 tangles in a 10 microns section) was also above the baseline level of the majority of cases. However, neuron loss was not widespread in these cases and none had shown evidence of cognitive impairment. The findings confirm that the early stages of Alzheimer's disease commonly occur amongst general hospital necropsies. The emergence of clinical signs of dementia appears to be related to the loss of a critical volume of neurons and not to tangle accumulation alone.

Dementia in the Oldest-Old:Quantitative Analysis of 12 Cases from a Psychiatric Hospital

“…Interestingly, a recent retrospective clinicopathologic evaluation of 1,258 elderly patients showed that up to 7.7% of cases displayed moderate to high NFT counts in this neocortical area in the absence of clinical signs of dementia [38]. As Hubbard et al [39], Hof et al [13], and Bouras et al [11,16] have suggested, it seems likely that numerous NFT in the inferior temporal cortex is a neuropathological finding characteristic of a possible preclinical stage of SDAT.…”

Regional Distribution of Neurofibrillary Tangles and Senile Plaques in the Cerebral Cortex of Elderly Patients: A Quantitative Evaluation of a One-Year Autopsy Population from a Geriatric Hospital

“…or psychiatric disorders (Tomlinson et al, 1968;Dayan, 1970;Terry et al, 1981;Mountjoy et al, 1983;Ulrich, 1985;Crystal et al, 1988;Katzman et al, 1988;Hubbard et al, 1990;Mann et al, 1990;Morris et al, 1991;Price et al, 1991;Arriagada et al, 1992a,b;Lippa et al, 1992;Vickers et al, 1992;Berg et al, 1993;Bouras et al, 1993). For example, Hubbard et al (1990) reported a neuropathological survey of 70 unselected cases from a general hospital.…”

“…For example, Hubbard et al (1990) reported a neuropathological survey of 70 unselected cases from a general hospital. In this series, four cases with documented evidence of cognitive impairment showed numerous NFTs in all neocortical areas examined, whereas six cases showing no signs of cognitive decline had excessive NFT formation confined to the hippocampal formation and temporal neocortex, but no NFTs in the other neocortical regions.…”

“…This difference in regional lesion distribution distinguishes these elderly nondemented cases from the Alzheimer's disease population, in which neocortical areas are devastated (Pearson et al, 1985;Lewis et al, 1987;Hof et al, 1990aHof et al, ,b, 1992Bouras et al, 1992). Most of the recent clinicoanatomic analyses of brain aging have been based on relatively small patient samples consisting of selected cases (Crystal et al, 1988;Katzman et al, 1988;Hubbard et al, 1990;Morris et al, 1991;Price et al, 1991;Arriagada et al, 1992a,b;. In the present study, we had the opportunity to survey all of the autopsied cases from a geriatric hospital for the year 1989.…”

“…More recently, several studies have demonstrated that amyloid deposition and NFT formation not only are common features of brain aging, but are found in certain regions of the cerebral cortex in densities that would qualify for a neuropathologic diagnosis of Alzheimer's disease cases (Crystal et al, 1988;Katzman et al, 1988;Hubbard et al, 1990;Price et al, 1991;Arriagada et al, 1992a,b;Berg et al, 1993;Bouras et al, 1993). In particular, a careful analysis of such cases revealed that in this population, the hippocampal formation systematically displayed a moderate to severe involvement, whereas the neocortical areas were unaffected or showed very low densities of NFTs and SPs Arriagada et al, 1992a ;Berg et al, 1993;Bouras et al, 1993).…”