Multiple Findings in Elderly Adults with Confirmed <scp>A</scp> lzheimer's Disease

The latest guidelines for diagnosing Alzheimer's disease (AD) that work groups of the National Institute on Aging and the Alzheimer's Association have developed1 recommend using amyloid positron emission tomography (aPET)2 and cerebrospinal fluid biomarkers.3 Because the U.S. Food and Drug Administration requires autopsy analysis as part of its aPET trials, autopsy confirmation is essential for putting together evidence of actual AD features. Because Japanese clinicians and researchers have had a greater opportunity to study the progression of the disease over a longer period because of patient longevity, cases often have combined neuropathological features, which makes it difficult to diagnose the distinct disease entities involved. The Fukushimura Brain Bank was established in 1990 and has published annual reports for longer than a decade.4 In recent years, a large number of cases have been accumulated, and several of the findings have changed the understanding of newly described neurodegenerative diseases affecting elderly adults, especially dementia with Lewy bodies5 and argyrophilic grain disease.6 The 108 cranial autopsies performed from December 2003 to June 2009 included 43 men and 65 women with an age at death of 84 ± 9.1. The majority of patients satisfied diagnostic criteria for more than one disease. Several had multiple types of changes in their brain. Thirty-seven definite AD cases met National Institute on Aging and Reagan criteria for a high7 likelihood of AD, and many of these had another pathology. Non-AD cases were also complicated. Vascular troubles (VT) were encountered the most frequently (64 cases, 59%). Of neurodegenerative diseases, AD pathology was the most common (37 cases, 34%). As a result, AD and VT were often seen together, and several cases had a third pathological feature. None of these cases had a familial history of AD. There were 10 cases of pure AD, without any other pathological change, and these had a significantly younger onset, shown as diamonds (Group (G) 1) in Figure 1. The other 27 cases had a vascular or other neurodegenerative disease. On looking at the relationship between onset age and duration, individuals with AD with VT (G2, G6, and G7) were aged 70 to 90 and had a 5- to 15-year duration, with no correlation observed. In individuals without VT (G1, G3, G4, and G5), there was a negative correlation between these two factors. Individuals with a later onset had a shorter duration and a tendency to develop more complications. When AD developed before the age of 70, it was generally of longer duration and was not accompanied by any other brain disease. The hypothesis is that younger individuals with AD were admitted for behavioral and psychological symptoms of dementia, so they had an early start at a controlled lifestyle, especially with respect to diet, and this nutritional support was maintained even in cases of advanced AD. Consequently, they had a lower risk of cerebrovascular disease and benefited from nutritional support to the end. Nevertheless, it was not possible to determine precisely why these individuals with younger onset and longer duration did not develop other neurodegenerative diseases. There were no cases with an onset at the age of 70 in individuals with AD with VT. Individuals with earlier onset of VT might have severe risk factors that would affect their prognosis, and they might not survive long enough to develop AD. It was learned that onset age and disease duration have an inverse correlation in cases of AD without VT (Figure 1), which means that AD is not a life-threatening disease per se, but the later onset and longer duration of AD has meant that individuals can develop multiple complications, making the clinical diagnosis of AD difficult. Japan is a super-aging society, and dementia, such as AD, is increasing rapidly in the population aged 80 and older. The older the individuals, the greater the risk of developing multiple dementia complexes with unaccountable clinical features. This study was conducted in accordance with the Helsinki Declaration. The ethical committee of Fukushimura Hospital approved the study protocol, and written informed consent was obtained from all participants or their relatives (approval number 039; June 2, 2000). Conflict of Interest: This study was supported by a grant from the Japanese Brain Bank Network for Neuroscience Research. The results were submitted for presentation at the Alzheimer's Association International Conference, Vancouver, British Columbia, Canada, July 14–19, 2012. Author Contributions: All authors participated in study concept and acquisition of data. Sponsor's Role: None.

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