M,Wan

Jetal.Effectsoftumornecrosisfactorgene polymorphisms on patients with congestive heart failure. VEST Investigators for TNF Genotype Analysis. Vesnarinone Survival Trial. Circulation

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In conclusion, there was no difference in the distribu- tion of the TNF  308 G4A polymorphism between cen- tenarians, young controls, and octogenarians, but in centenarians, the GA genotype was associated with low prevalence of dementia. It appears that the TNF  308 A allele is maintained during aging because subjects who are heterozygous for this polymorphism posses the optimal in- flammatory response against chronic degenerative process- es in the CNS.

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Appendix 1

The diagnosis of dementia was made according to criteria of the International Classification of Diseases (ICD-10) by the World Health Organization, which includes the pattern of daily activities. Every subject was checked in detail for the following variables, which were used to make the ICD-10 criteria operationally as previously described:2

G1(1): A decline in memory: Proxy information regard- ing changes in short-term and long-term memory, ability to recognize other people, find the way home, recall the time of the year; questions regarding orientation and re- call in the Mini-Mental State Examination (MMSE), ability to answer questions in a sociodemographic interview.

G

(

): A decline in other cognitive abilities: proxy infor- mation regarding the ability to understand messages and make decisions, judgment, and orientation; MMSE ques- tions regarding attention, learning, serial subtractions or reverse spelling, constructional capacities, use of lan- guage; ability to perform activities of daily living (ADLs) and instrumental ADLs (IADLs). G

: Awareness of the environment: clinical assessment. G

: Decline in emotional control/motivation or change in social behavior: proxy information and clinical judgment. G

: Presence for at least

months: proxy information.

were interfering with IADL items. The specific domains of memory, orientation, and judgments plus problem solving in the CDR were assessed using the same tools as used in the ICD-10. The more complex domain of community affairs was assessed using the ability to make decisions about shopping and financial affairs, whereas the domain of home and hobbies was assessed using information regarding in- terest in reading or having the newspaper or books read aloud, housework, gardening, or hobbies. An extra group (7%) was added as ‘‘probably no dementia,’’ consisting of centenarians in whom sensory deficits or unwillingness to perform all the items in the MMSE made it difficult to rate them as nondemented according to the strict criteria, whereas all other information indicated normal cognitive function. In the present study, only two categories of de- mentia were used: nondementia (healthy, questionable de- mentia, probably no dementia) and dementia (mild, moderate, and severe dementia). Diagnoses of depression and schizophrenia/chronic psychotic diseases were re- trieved from medical records.

Further support: apraxia, agnosia, aphasia; ability to ognize other people; MMSE questions regarding naming of objects; and IADLs.

The severity of dementia was rated according to the five-level Clinical Dementia Rating scale (healthy, ques- tionable, mild, moderate, and severe dementia). The eval- uation of job functioning was excluded. In each case, a distinct evaluation was made of whether physical handicaps