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Objectives Factors accelerating cerebral degenerative changes represent potentially modifiable risks for cognitive decline. Putative risk factors accelerating subtle cognitive decline and dementia were correlated with repeated measures of cerebral atrophy, CT densitometry, perfusions and cognitive testing among neurologically and cognitively normative ageing volunteers. Methods Two hundred and twenty‐four normative subjects at increased risk for cognitive decline were admitted to the study. Mean entry age was 59.5±15.8 years. Mean follow‐up is 4.3±3.1 years. At follow‐up, 22 developed subtle cognitive decline (δCCSE≥−3), 19 became demented, eight with vascular type (VAD) and 11 with Alzheimer's type (DAT) and 183 remain cognitively unchanged. Standardized questionnaires, medical, neuropsychological, neurological and blood work examinations were obtained. Cerebral atrophy, tissue densities and perfusions were measured by xenon‐enhanced CT. Results After age 60, cerebral atrophy, ventricular enlargement, polio‐ and leuko‐araiosis geometrically increased as perfusions declined. Risk factors accelerating perfusional decline, cerebral atrophy, polio‐araiosis and leuko‐araiosis (thinning of grey–white matter densities) were: transient ischaemic attacks (TIAs), hypertension, smoking, hyperlipidemia, male gender. At age 71.5±11.9, subtle cognitive decline began, accelerated by TIAs, hypertension and heart disease. Leuko‐araiosis began before cognitive decline. TIAs, hypertension and hyperlipidemia correlated with VAD. Excessive cortical perfusional decreases and cerebral atrophy correlated with cognitive decline. Family history of neurodegenerative disease correlated with DAT. Conclusion TIAs, hypertension, hyperlipidemia, smoking and male gender accelerate cerebral degenerative changes, cognitive decline and dementia. Copyright © 1999 John Wiley & Sons, Ltd.

Factors accelerating cerebral degenerative changes represent potentially modifiable risks for cognitive decline. Putative risks accelerating subtle cognitive decline and dementia were correlated with repeated measures of cerebral atrophy, CT densitometry, perfusions, and cognitive testing among 224 neurologically and cognitively normative aging volunteers. After age 60, cerebral atrophy, ventricular enlargement, polioaraiosis, and leukoaraiosis geometrically increased as perfusions declined. Risks accelerating perfusional decline, cerebral atrophy, polioaraiosis, and leukoaraiosis were: transient ischemic attacks (TIAs), hypertension, smoking, hyperlipidemia, male gender. At age 71.5 +/- 11.9, subtle cognitive decline began, accelerated by TIAs, hypertension, and heart disease. Leukoaraiosis began before cognitive decline. TIAs, hypertension, and hyperlipidemia correlated with vascular dementias. Excessive cortical perfusional decreases and cerebral atrophy correlated with cognitive decline. Family history of neurodegenerative disease correlated with Alzheimer's disease. We concluded that TIAs, hypertension, hyperlipidemia, smoking, and male gender accelerate cerebral degenerative changes, cognitive decline, and dementia.