American Journal of Medical Genetics 125A:315–317 (2004) Research Letter Mitotic Index in Down’s Syndrome With and Without Dementia To the Editor: Previously, we reported reduced mitotic indices (MIs) in skin fibroblast cultures from five individuals with Alzheimer’s Disease (AD) [Jenkins et al., 1998]. We have now found reduced MIs in short-term whole blood cultures from 12 of 15 individuals with trisomy 21 and dementia vs. 13 other non-demented trisomy 21 indivi- duals who were generally age- and sex-matched—X 2 (1) Yates corrected ¼ 11.69, P < 0.01 (Table I). A MI  25 suggested dementia while a MI > 25 suggested non- dementia. Only one of the 13 non-demented trisomy 21 individuals exhibited a MI of <25. When the two sets of data in Table I were compared using the t-test (STATISTICA 6.0), a P value of <0.0002 was obtained. The individuals in Table I ranged in age from 50 to 66 years. The mean age for individuals with dementia was 56.95 while it was 55.95 years for those without dementia. All classifications of dementia were consis- tent with criteria recommended by the Working Group for the Establishment of Criteria for the Diagnosis of Dementia in Individuals with Intellectual Disability, of the ‘‘American Association on Mental Retardation’’ and the ‘‘International Association for the Scientific Study of Intellectual Disability’’ [Aylward et al., 1997] and the World Health Organization [1992]. These individuals were participants in a longitudinal study of DS. The present study was conducted from archived, fixed specimens used to confirm trisomy 21 Down’s syndrome in the longitudinal study. Results of additional preliminary studies shown in Table II also exhibited reduced MIs in cultures from people not yet classified as having dementia but who were exhibiting mild declines. Similar to the results in Table I, an MI  25 suggested mild declines for indivi- duals listed in Table II while an MI > 25 suggested non- dementia (Fisher’s Exact test, P < 0.04 two-tailed). These individuals ranged in age from 50 to 73 years and the mean age of females with cognitive decline was 54.60 years while that for females with no cognitive decline was 53.4 and, similar to Table I were generally age- and sex-matched. They were classified (as were those listed in Table I) based upon evaluations of the health, functional, and cognitive status carried out for each subject at 14–18 month intervals to deter- mine if cognitive declines consistent with dementia were present. These evaluations included a comprehen- sive review of clinical records, interviews with knowl- edgeable informants providing objective descriptions of participants’ adaptive skills, health status and problem behaviors, and direct assessments of cognition explicitly designed for use with this population. Assessment of cognition was carried out using a battery of tests including: the Wisniewski and Hill [1985] modification of the Mini-Mental State Exam [Folstein et al., 1975]; the Test for Severe Impairment [Albert and Cohen, 1992]; a mental status evaluation developed by Haxby [1989] and Haxby and Schapiro [1992]; the Peabody Picture Vocabulary Test [Dunn and Dunn, 1981]; an adaptation of the McCarthy [1972] test of verbal fluency; the Beery Visual Motor Integration Test [Beery and Bukenia, 1989]; and an 8-item version of the Selective Reminding Test [Buschke, 1973]. The human subjects in Table I exhibited either definite dementia, indicating that ICD-10 criteria [International Statistical Classification of Diseases; World Health Organization, 1992] were met and sub- stantial declines over time were documented or they were not demented indicating that ICD-10 criteria for dementia were not met. The human subjects listed in Table II were either not demented or they were classified as questionable, indicating the presence of some evi- dence consistent with mild functional or cognitive dec- line, but not of sufficient severity to suggest a diagnosis of dementia (mild declines). Our findings provide a preliminary indication that reduced MI is associated with dementia and cognitive decline in adults with DS. In light of our preliminary results, this association is likely to be strong, and given that we are focusing on adults with DS, this association is likely to be caused by the progression of AD/dementia. We will now evaluate additional subjects with dementia or with preliminary signs that may lead to dementia, Grant sponsor: NYS Office of Mental Retardation and Devel- opmental Disabilities, Alzheimer’s Association Grant; Grant number: IIRG-99-1598; Grant sponsor: NIH; Grant numbers: PO1 HD35897, HD37425, RO1 AG014673. *Correspondence to: Edmund C. Jenkins, Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY, 10314-6639. E-mail: ecjenkins@erols.com Received 26 March 2003; Accepted 23 June 2003 DOI 10.1002/ajmg.a.20453 ß 2003 Wiley-Liss, Inc.