BACKGROUND: Comorbidity between depression and cognitive impairment is common in older adults, increases the disease burden disproportionally, and leads to diagnostic uncertainty. Insight into individual daily associations between affect and cognitive performance may help in personalizing diagnosis and treatment decisions. Our objective was to get insight into the daily associations between affect and cognitive performance within individual older adults. METHODS: In this single-subject study seven older adults with both depression and cognitive impairment filled in electronic diaries daily for 62-93 consecutive days evaluating positive affect (PA), negative affect (NA), working memory (WM) and visual learning (VL). Time-series analyses using vector autoregressive modelling, Granger causality tests and cumulative orthogonalized impulse response function analyses were performed for each individual separately. RESULTS: In one patient higher NA was associated with better WM the next day. For another patient days with higher NA and lower PA were days with worse WM. For a third patient better VL was associated with lower NA and higher PA the next day. No associations were found for four patients. CONCLUSIONS: These results highlight heterogeneity in the daily associations between affect and cognitive performance and stress the relevance of single-subject studies. These studies may be an important step towards personalized diagnosis and treatment in old age psychiatry.