Telomere shortening reflecting physical aging is associated with cognitive decline and dementia conversion in mild cognitive impairment due to Alzheimer's disease

We investigated whether telomere length (TL) reflecting physical rather than chronological aging is associated with disease progression in the different cognitive stages of Alzheimer's disease (AD). Study participants included 89 subjects with amyloid pathology (A+), determined through amyloid PET or cerebrospinal fluid analysis, including 26 cognitively unimpaired (CU A+) individuals, 28 subjects with mild cognitive impairment (MCI A+), and 35 subjects with AD dementia (ADD A+). As controls, 104 CU A-individuals were selected. The participants were evaluated annually over two years from baseline. Compared to the highest TL quartile group of MCI A+ participants, the lowest TL quartile group yielded 2-year differences of-9.438 (95% confidence interval [CI] =-14.567 ~-4.309),-26.708 (-41.576 ~-11.839), 3.198 (1.323 ~ 5.056), and 2.549 (0.527 ~ 4.571) on the Mini-Mental State Examination, Consortium to Establish a Registry for AD, Clinical Dementia Rating-Sum of Boxes, and Blessed Dementia Scale-Activities of Daily Living, respectively. With this group, the lowest TL quartile group had a significantly greater probability of progressing to ADD than the highest TL quartile group (hazard ratio = 13.16, 95% CI = 1.11 ~ 156.61). Telomere shortening may be associated with rapid cognitive decline and conversion to dementia in MCI A+.