We investigated 150 centenarians (130 women and 20 men) aged 100–107, mean age 101.1 ± 1.1 years, who participated in the multicenter scientific project “Genetic and Environmental Factors

of Longevity of Polish Centenarians” (PolStu), coordinated by the International Institute of Molecular and Cellular Biology in Warsaw. The individuals were not related. The recruitment of the participants and their general clinical evaluation are described by Mossakowska et al.31

refusal to participate in testing or the participant was otherwise uncooperative.

As controls, we tested DNA samples from 165 blood donors aged 18–56, mean age 27.8 ± 9.1 years; 91 women and 74 men, obtained from the Department of Paediatrics, Oncology, Haematology and Diabetology, Medical University of Lodz. These subjects are assumed to represent the same source popula- tion as the centenarians, but with little selection for mortality.

In the present study we used data on cognitive performance extracted from the existing database. Cognitive status was known for 115 centenarians. In 82 individuals severe cognitive impairment had been defined according to the following criteria: (1) clinical diagnosis of dementia done by a neurologist with the use of the established international criteria: DSM IV,32 NINCDS/ ADRDA,33,34 ICD 1034 and Hachinski Ischemic Scale;35 (2) the CDR score of 1 or above; or (3) the MMSE score of 60% or below of a maximum possible score (if clinical diagnosis or CDR score was not available).

The study was performed according to accepted ethical dards and formal approval from the Human Subjects Board.

Genotype for the PRNP codon 129 was determined using an established PCR-RFLP method.36 We investigated Hardy- Weinberg Equilibrium (HWE) for the centenarians and for the control subjects. Genotype frequency distributions, and allele frequencies, found for the two subject groups were contrasted using chi-square test. Additionally, Cochran-Armitage test for trend in allele dose (0, 1, 2 alleles) with the use of Monte Carlo method (performed using the XLStat software) was carried out. Statistical significance was assumed at p ≤ 0.05 (two-sided).

In centenarians the maximum MMSE score was established for every person separately, considering his/her age-associated disabilities, such as vision problems. The maximum possible scores differed between the analyzed individuals, so we used the percentages instead of absolute cut-off values.

The criteria of dementia—listed in points 1 and 2—were sat- isfied for 45 centenarians (35 AD patients, 1 vascular dementia and 9 cases of mixed dementia). The subgroup classified accord- ing to point 3 included 37 subjects.

No potential conflicts of interest were disclosed.

Acknowledgments

A determination of no severe cognitive impairment was made for 33 centenarians known to have CDR score of 0 or 0.5 or MMSE score of 80% or above of a maximum possible score (when CDR not available). Thirty-five centenarians remained unclassifiable. Among them, 19 subjects did not meet any of the above criteria, and in 16 cases, the cognitive status was not assessed due to several typical reasons: deafness, nei- ther cognitive testing nor interviews were possible, there was

The study was supported by the State Committee for Scientific Research (KBN) grants no. PBZ-KBN-022/PO5/1999 (collec- tion of samples and clinical characterization of centenarians), 2P05 B08430 (genotyping) and funds of Medical University of Lodz and503/1-034-04/503-01. Prof Shirley Lindenbaum (Graduate Center City University of New York) is kindly acknowledged for assistance with preparation of the manuscript.

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