Non-genetic risk and protective factors for sporadic degenerative and vascular young onset dementia

Abstract

Young onset dementia (with symptom onset before age 65, YOD) has a significant personal and public health impact. Despite this, little is known about its cause and non-genetic factors have been sparsely investigated. Existing studies have not considered the timing or severity of exposure, which is important in late onset dementia (LOD). They have also failed to exclude directly-inherited cases and those occurring secondarily to another disease. This thesis examined the risk for sporadic degenerative and vascular YOD associated with six selected non-genetic factors: cognitive reserve enhancing factors, cardiovascular risk factors, smoking, depression, alcohol use, and traumatic brain injury (TBI). It established the role of exposure timing and severity, as well as interrelationships existing between factors. Data were taken from two epidemiological studies conducted in Sydney, Australia, one of which exclusively included Aboriginal and Torres Strait Islander participants. Dementia diagnosis was confirmed via clinical consensus and risk exposure was retrospectively self- and/or informant-reported. Participants were 96 people with YOD (58.4% with Alzheimer’s disease) and 179 age-group and sex matched control participants. Poor educational attainment, low lifetime participation in cognitive leisure activity, stroke or TIA, smoking, and heavy alcohol use were significantly related to risk for primary degenerative and vascular YOD. Some compensation for low educational attainment was possible via a complex occupation later in life. The effect of hypertension and depression varied depending on when they occurred relative to dementia onset. There was no effect of mild-moderate alcohol use, hypercholesterolemia, diabetes, or TBI of any kind. Cumulative risk exposure was detrimental, particularly where lack of access to or participation in cognitive-reserve enhancing factors clustered with cardiovascular risk factors. The results of this thesis suggest that non-genetic factors have a role in YOD as they do in LOD. Compared with their same-age peers, people with YOD experience a lifetime of disadvantage starting from early in life. The timing and severity of exposure, as well as the potential for compensation with later protective exposures, are important considerations. Efforts to address early life disadvantage and facilitate upward social mobility will be beneficial in delaying dementia to later in life