Neuropathologic Findings of Dementia with Lewy Bodies (DLB) in a Population-based Vantaa 85+ Study

Abstract

The consortium on dementia with Lewy bodies has established consensus guidelines for the neuropathologic diagnosis of dementia with Lewy bodies (DLB) including the likelihood that the neuropathologic findings associate with the clinical syndrome. Nevertheless, clinico-pathological correlations remain controversial. We applied the consensus guidelines for determining Lewy-related pathology (LRP) and evaluated the clinical presentation in the prospective, population-based Vantaa 85+ study consisting of individuals at least 85 years of age. LRP was seen in 36% of 304 subjects and categorized as follows: 3% brainstem-predominant, 14% limbic, 15% diffuse neocortical type (4% could not be categorized). The likelihood that the neuropathology predicts the DLB clinical syndrome was low in 6%, intermediate in 13%, and high in 13% of all 304 subjects. In the latter two groups, 77% were demented, 35% had at least one extrapyramidal symptom, and 15% had visual hallucinations. Surprisingly, DLB clinical features associated better with high neurofibrillary stage than with diffuse neocortical LRP. Moreover, the neurofibrillary stage, substantia nigra neuron loss, and grade of Lewy neurites in hippocampal CA2-3 region, each showed a significant association with the extent of LRP. In conclusion, the neuropathologic DLB in this very elderly population was common, but the clinical symptoms tended to associate better with severe neurofibrillary pathology than with extensive LRP.

Prevalence and Pathology of Dementia with Lewy Bodies in the Oldest Old: A Comparison with Other Dementing Disorders

“…In the clinical intermediate- and high-probability group (26%), 77% were demented, 25% had at least 1 extrapyramidal symptom, and 15% had hallucinations. The authors concluded that DLB in this very elderly population was common, but the clinical symptoms better tended to be associated with severe neurofibrillary pathology than with the extent of Lewy-related pathology [41], partly confirming previous findings [67]. …”

“…However, we included only patients with MMSE scores of <20 and a DSM-IV diagnosis of dementia because the possibility of making a wrong diagnosis of dementia is lower in moderate-to-severe forms. Another limit is the fact that the results of this retrospective, hospital-based study are difficult to compare with those of population-based studies [41]. However, the finding that DLB (without severe Alzheimer pathology) as well as the severity of Lewy pathology – in contrast to AD (with and without other pathologies) and mixed dementia – slightly decrease with advancing age appears of both clinical and pathological interest.…”

“…In the recent population-based Vantaa 85+ study, Lewy-related pathology was seen in 36% of 304 subjects (mean age: 92.5 years) and categorized as follows: 3% brainstem predominant, 14% limbic, 15% diffuse neocortical type (4% nonclassifiable) [41]. In the clinical intermediate- and high-probability group (26%), 77% were demented, 25% had at least 1 extrapyramidal symptom, and 15% had hallucinations.…”

“…Classical AD-related neuropathology (plaques and tangles) was associated with cognitive impairment in young AD patients (70–89 years), while synaptophysin immunoreactivity correlated better with cognitive impairment in older DLB and AD patients (90+ years) [39]. In recent population-based studies of subjects aged over 85 years, Lewy pathology was observed in 31–37% of cases, the majority classified as limbic or diffuse neocortical DLB [40,41,42]. The aim of the present study was to retrospectively examine the frequency and pathology of DLB and other dementing disorders in very old age.…”

Neuropathologic features associated with Alzheimer disease diagnosis

“…[5][6][7][8][9][10][11][12][13][14][15] Preliminary studies that compared the strength of association between dementia diagnosis or cognitive performance and AD neuropathology (neuritic plaques and neurofibrillary tangles) between the young old and the oldest old suggest that the association is weaker among the oldest old 6,13 ; however, these studies were limited by small to moderate size and considered…”