Clustering and Additive Effects of Nongenetic Risk Factors in Non-Autosomal-Dominant Degenerative and Vascular Young Onset Dementia.

INTRODUCTION: Both genetic and nongenetic factors contribute to the risk profile of young onset dementia (YOD), but risk factors often co-occur. This matched case-control study examined whether nongenetic risk factors cluster together, to inform targeted prevention efforts. METHODS: Ninety-six participants with non-autosomal-dominant degenerative and/or vascular YOD and 175 controls were recruited to 2 Australian epidemiological studies. Risk exposure was retrospectively self-reported and/or informant-reported. RESULTS: Each additional exposure increased the risk for YOD, though only where vascular dementia was included in the analysis. Cluster analysis identified 4 risk groups, one of which reported a high probability of exposure to all risks and a significantly higher risk for YOD. DISCUSSION: Results suggest that combinations of nongenetic risk factors confer more risk for young onset vascular dementia, and possibly primary degenerative YOD, than a single factor on its own. Compared with their same-age peers, some people with YOD experience a lifetime of risk exposure starting from early in life.

Non-Genetic Risk Factors for Degenerative and Vascular Young Onset Dementia: Results from the INSPIRED and KGOW Studies.

BACKGROUND: Several brain reserve, vascular risk, and other modifiable factors have been associated with late-onset dementia, but their association with young onset dementia (YOD) has not been adequately explored. OBJECTIVE: To examine the association of cognitive reserve enhancing factors, cardiovascular risk factors (including smoking), depression, alcohol use, and traumatic brain injury (TBI) with non-autosomal dominant degenerative and/or vascular YOD. METHODS: Data for this matched case-control study were taken from two larger studies conducted in NSW, Australia. One comprised all people with YOD within a geographical region, while the other exclusively included Aboriginal and Torres Strait Islander participants. Dementia diagnosis was confirmed by clinical consensus, and risk exposure was retrospectively self- and/or informant-reported. RESULTS: Participants were 96 people with YOD (58.4% with probable Alzheimer's disease) and 175 age-group, sex, and sample matched control participants. Poor educational attainment, low participation in cognitive leisure activity, stroke, transient ischemic attack, and self-reported very heavy alcohol use were related to the risk of primary degenerative and/or vascular YOD. The effect of hypertension and depression varied depending on when they occurred relative to dementia onset. Current smoking was significantly associated with risk in univariate analyses but did not retain significance in multivariate modelling. There was no association with hypercholesterolemia, diabetes, or TBI of any kind. Some compensation for low educational attainment was possible via a complex occupation later in life. CONCLUSION: Non-genetic factors have a role in YOD, though the relative importance of each factor may be different to late onset dementia. The timing and severity of exposure, as well as the potential for compensation with later protective exposures, are important considerations for potential prevention strategies.

Clinical diagnostic criteria for dementia associated with Parkinson's disease.

Dementia has been increasingly more recognized to be a common feature in patients with Parkinson's disease (PD), especially in old age. Specific criteria for the clinical diagnosis of dementia associated with PD (PD-D), however, have been lacking. A Task Force, organized by the Movement Disorder Study, was charged with the development of clinical diagnostic criteria for PD-D. The Task Force members were assigned to sub-committees and performed a systematic review of the literature, based on pre-defined selection criteria, in order to identify the epidemiological, clinical, auxillary, and pathological features of PD-D. Clinical diagnostic criteria were then developed based on these findings and group consensus. The incidence of dementia in PD is increased up to six times, point-prevelance is close to 30%, older age and akinetic-rigid form are associated with higher risk. PD-D is characterized by impairment in attention, memory, executive and visuo-spatial functions, behavioral symptoms such as affective changes, hallucinations, and apathy are frequent. There are no specific ancillary investigations for the diagnosis; the main pathological correlate is Lewy body-type degeneration in cerebral cortex and limbic structures. Based on the characteristic features associated with this condition, clinical diagnostic criteria for probable and possible PD-D are proposed.