Normal human aging: factors contributing to cerebral atrophy

Factors that accelerate rates of 'normal' age-related cerebral atrophic and degenerative changes are important because they may predispose to cognitive declines. To determine characteristic patterns of normal aging, risk factors were correlated with serial neurological-neuropsychological examinations, CT measures of progressive cerebral atrophy, local tissue hypodensities, or perfusional declines. Both cross-sectional and longitudinal designs were utilized. Ninety-four cognitively and neurologically normal aging volunteers, 15 with a history of transient ischemic attacks (TIAs), were followed for mean intervals of 3.0+/-2.1 years. Results indicated that: (1) after age 60, cerebral atrophy, polio- and leuko-araiosis doubled and cerebral perfusion decreased, with marked individual variations; (2) risk factors independently accelerating cerebral atrophy and cortico-subcortical perfusional declines included TIAs, hypertension, smoking, hyperlipidemia, excessive alcohol consumption and male gender; (3) progressive leuko-araiosis correlated directly with cortical atrophy and cortical perfusional declines. We posit that: (1) cerebral atrophy and degenerative changes result from neuronal shrinkage and/or loss, which are accelerated by TIAs, hypertension, smoking, hyperlipidemia, excessive alcohol consumption and male gender; (2) accelerated cerebral atrophic and degenerative changes identified by neuroimaging should be considered as markers for depleted neuronal synaptic reserves, which predispose to cognitive declines. Interventions available for controlling some of these risk factors include control of TIAs, hypertension, and hyperlipidemia, as well as tobacco and alcohol withdrawal.