Apathy and the Risk of Predementia Syndromes in Community-Dwelling Older Adults

Objectives Apathy is a potential predictor of dementia in older adults, but this investigation has been limited to older adults with a preexisting neurological illness like mild cognitive impairment (MCI), stroke or Parkinson’s disease. The objective of this study was to investigate the association between apathy at baseline and incident predementia syndromes, including MCI and motoric cognitive risk syndrome (MCR), subjective cognitive complaints and slow gait, in community-dwelling older adults. Method We prospectively studied the association between apathy (using the 3-item subscale of the Geriatric Depression Scale [GDS3A]) and incident cognitive disorders in 542 community-dwelling older adults enrolled in the Central Control of Mobility in Aging study using Cox proportional hazard models. Associations were reported as hazard ratio (HR) with 95% confidence intervals (CIs), adjusting for age, education, baseline cognitive performance, and depressive symptoms. Results Apathy was associated with incident MCR (HR 2.39, 95% CI: 1.10–5.20), but not predementia syndromes overall nor MCI. In sensitivity analyses of MCI subtypes, apathy was associated with nonamnestic MCI (HR 2.44, 95% CI: 1.14–5.22), but not amnestic MCI. Our study was limited by a short follow-up time (median 13.6 months; interquartile range 29.8) and a brief subscale measurement of apathy, GDS3A. Discussion In our study, apathy predicted MCR but not MCI in community-dwelling older adults. These results and the current literature suggest that apathy is an early risk factor for dementia. Additionally, apathy may be a novel treatment target that could forestall the disability of dementia.

Dietary Fatty Acids and Predementia Syndromes

An increasing body of epidemiological evidence suggests that elevated saturated fatty acids (SFA) could have negative effects on age-related cognitive decline (ARCD). Furthermore, a reduction of risk for cognitive decline and mild cognitive impairment (MCI) has been found in population samples with elevated fish consumption, and high intake of monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA), particularly n-3 PUFA. However, recent findings from clinical trials with n-3 PUFA supplementation showed efficacy on depressive symptoms in non–Vapolipoprotein E (APOE) ε4 carriers, and on cognitive symptoms only in very mild Alzheimer's disease (AD) subgroups, MCI patients, and cognitively unimpaired non-APOE ε4 carriers. These data, together with epidemiological evidence, support the idea that n-3 PUFA may play a role in maintaining adequate cognitive functioning in predementia syndromes, but not when the AD process has already taken over. Therefore, at present, no definitive dietary recommendations on fish and unsaturated fatty acids consumption, or lower intake of saturated fat, in relation to the risk for dementia and cognitive decline are possible.

Polyunsaturated Fatty Acid and S-Adenosylmethionine Supplementation in Predementia Syndromes and Alzheimer's Disease: A Review

A growing body of evidence indicates that nutritional supplements can improve cognition; however, which supplements are effective remains controversial. In this review article, we focus on dietary supplementation suggested for predementia syndromes and Alzheimer’s disease (AD), with particular emphasis on S-adenosylmethionine (SAM) and polyunsaturated fatty acids (PUFA). Very recent findings confirmed that SAM can exert a direct effect on glutathione S-transferase (GST) activity. AD is accompanied by reduced GST activity, diminished SAM, and increased S-adenosylhomocysteine (SAH), the downstream metabolic product resulting from SAM-mediated transmethylation reactions, when deprived of folate. Therefore, these findings underscored the critical role of SAM in maintenance of neuronal health, suggesting a possible role of SAM as a neuroprotective dietary supplement for AD patients. In fact, very recent studies on early-stage AD patients and moderate- to late-stage AD patients were conducted with a nutriceutical supplementation that included SAM, with promising results. Given recent findings from randomized clinical trials (RCTs) in which n-3 PUFA supplementation was effective only in very mild AD subgroups or mild cognitive impairment (MCI), we suggest future intervention trials using measures of dietary supplementation (dietary n-3 PUFA and SAM plus B vitamin supplementation) to determine if such supplements will reduce the risk for cognitive decline in very mild AD and MCI. Therefore, key supplements are not necessarily working in isolation and the most profound impact, or in some cases the only impact, is noted very early in the course of AD, suggesting that nutriceutical supplements may bolster pharmacological approaches well past the window where supplements can work on their own. Recommendations regarding future research on the effects of SAM or n-3 PUFA supplementation on predementia syndromes and very mild AD include properly designed RCTs that are sufficiently powered and with an adequate length (e.g., 3–5 years of follow-up).