People 65 years old and older are at increased risk of fatal automobile accidents. These accidents occur predominantly at intersections, where the cognitive load on the driver is increased. Alzheimer's disease (AD) is the most common cause of impaired cognitive function in the elderly and its prevalence increases with age. In addition, carriers of the £4 allele of apolipoprotein E (APOE) gene have a two-fold to fivefold higher risk of developing late-onset AD.' Because of the insidious onset of AD, affected people do not generally seek medical advice during the early stages, and if they do, the physician may not recognise early cognitive impairment. Neuropathological characteristics of AD are senile plaques, especially of the neuritic type and neuro:fibrillary tangles.' The presence of the £4 allele increases the load of senile plaques. To assess whether AD contributes to fatal automobile accidents, we analysed the frequency of neuropathological changes of AD as well as of £4 allele in older drivers who were killed. Results of neuropathological examinations on 98 drivers aged 65 years and older (mean 75·2, range 65-90 years) killed in traffic accidents in Sweden and southwestern Finland between June, 1992, and January, 1995, were obtained. Bielschowsky-stained sections from two regions of associative cortex-middle frontal and angular parietal gyri-which are involved in decision-making, judgment, and visual and spacial ability, and which are included in the CERAD criteria for AD' were examined. The density of neuritic plaques and number of neurofibrillary tangles were assessed independently by two neuropathologists according to CERAD criteria (inter-rater correlations K=0·80), modified by translating CERAD's serniquantitative rating into numerical values (figure). In 70 of the 98 drivers APOE genotypes were determined from leucocytes by microsequencing on microtitre plates (AffiGen APOE, Sangtec Medical, Stockholm, Sweden). Age-matched and sex-matched paired controls were randomly selected from previous studies of APOE in Sweden. 33% of killed drivers had neuritic plaque scores that make a histological .diagnosis of AD certain, and in a further 20% histopathological findings suggest AD (figure). In 17% of cases, at least one neurofibrillary tangle was found in the parietal or frontal cortex. Allele £4 was found more often in killed drivers than in controls (Wilcoxon test, p=0·029). The APOE genotype £4 did not affect the number of neuritic plaques found. Increasing age was associated with increasing numbers of neuritic plaques (Manova test, p=0·971 and p=0·026, respectively). CERAD criteria are widely used in the diagnosis of AD, and they correlate well with cognitive decline and clinical findings.• According to CERAD, a clinical history of dementia is required for definite or probable diagnosis of AD. Without a clinical history of dementia, possible AD can be diagnosed, if the age-related neuritic plaque-score either indicates or suggests AD. Depending on the cut points between the categories of neuritic plaque-scores in 33% and 14% of our cases, respectively, age-related plaque scol'.es indicate AD. Furthermore, in an additional 20% and 33%, respectively, the plaque score suggest AD. It is possible that 47-53% of drivers killed may have had incipient AD. The presence of neurofibrillary tangles in 17%, as well as a higher frequency of APOE £4 allele among the drivers killed over 75 years old compared with controls further supports the possibility of AD. It has been shown that people with mild AD have impaired performance in traffic, and that those with dementia have more accidents than age-matched controls.' Older drivers involved in accidents should have their cognitive performances tested; and older drivers themselves, their relatives, and physicians should be on the lookout for early symptoms of impaired cognition which would increase the risk of automobile accidents. (Author/publisher)
Samenvatting