Is there pure vascular dementia in old age?

Abstract

Vascular dementia (VaD) has been suggested to be the most common form of dementia in old age, but clinico-pathologic studies showed big differences in its epidemiology. A retrospective hospital-based study of the frequency and pathology of “pure” VaD (due to cerebrovascular disease without other pathologies) was performed in 1110 consecutive autopsy cases of demented elderly in Vienna, Austria. It assessed clinical, general autopsy data and neuropathology including immunohistochemistry. Neuropathologic diagnosis followed current consensus criteria. Four age groups (7th to 10th decades) were evaluated. “Pure” VaD was observed in 10.8% of the total cohort, decreasing from age 60 to 90+. 85–95% had histories of diabetes, morphologic signs of hypertension, 65% myocardial infarction/cardiac decompensation, and 75% a history of stroke(s). Neuritic AD-pathology was low (mean Braak stages 1.2–1.6). Morphologic subtypes (multi-infarct (MID), subcortical arteriosclerotic (SAE)—the most frequent, and strategic infarct dementia (SID)) showed no age-related differences. By contrast, AD (without vascular or Lewy pathologies), mixed dementia (AD + cerebrovascular encephalopathy), and AD with minor cerebrovascular lesions increased with age. AD + Lewy pathology and other dementias decreased significantly over age 90. This retrograde study using strict morphologic diagnostic criteria confirmed the existence of “pure” VaD in old age, with a tendency to decline at age 90+, while AD and AD + cerebrovascular pathologies showed considerable age-related increase. Another autopsy study distinguishing two age groups of demented showed a significant increase of both AD and cerebral amyloid angiopathy (CAA), but decrease of VaD over age 85, while in a small subgroup of old subjects CAA without considerable AD-pathology may be an independent risk factor for cognitive decline.

Introduction

Cerebrovascular lesions, mainly lacunes, microinfarcts and white matter lesions (WML) are common in elderly patients with cognitive impairment or dementia. Vascular dementia (VaD, [1]) or vascular cognitive impairment (VCI, [2]) has been suggested to be the most common form of dementia in the elderly [3], but previous studies showed big differences. Given the difficulties in diagnosing VaD, considerable methodological and geographical differences, there is considerable lack of agreement about its epidemiology. In clinical studies the prevalence of VaD ranges from 4.5 to 39% [4], in Western memory clinical- and population-based series it averages 8–19% [5], with standardized incidence rates (SIR) between 0.42 and 2.68. Pathologic studies showed enormous differences in prevalence ranging from 0.03 to 85.2% with means around 11% (see [6]), while in recent Japanese geriatric autopsy series, it was 23.6 to 35% [7], [8]. Both the prevalence and incidence of VaD increase with age [9], [10], [11], [12], [13], [14]. In clinical studies around Europe VaD between age 65–69 and 80+ years ranged from 2.2 to 16.3%, 20–40 to 200–700/100,000 [14] and 0.7 to 6–8.1/1000 person-years [15]; and 39.0/1000 person-years at age 85–88 [9]; in USA from 0.2 to 16% [16] or 3.9 to 19.1% [17], with a double specific incidence at age 80+ in Afro-Americans compared to Caucasians [18], while in Japan the prevalence of VaD decreased after age 85+ (from 5.3 to 3.9%) [19]. In Canada, the prevalence of clinically diagnosed AD vs VaD increased significantly after age 65 and was higher in the 85+ group than in the younger cohort [20]. In China, the prevalence for ages 65+ was 4.8% for AD and 1.1% for VaD, with age-related increase in AD from 0.5 to 3.5%, while the prevalence of VaD, after an increase up to 4% in the 9th decade, rapidly decrased after age 90 years [21], [22]. The epidemiologic studies, however, must be interpreted cautiously due to referral biases, impediment of their comparison by the lack of common diagnostic criteria for VaD and the fact that aged subjects with and without dementia show a high frequency of mixed pathologies [23], [24], [25], [26], [27], [28] (see Table 1). In autopsy series, the prevalence of VaD between age 70 and 90+ increased from 13 to 44.6%, compared to Alzheimer disease (AD) (23.6 to 51%) and mixed dementia (2 to 46.4%) (see Table 2). The aim of the present study was to examine retrospectively the frequency and pathology of VaD in old age.