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The spatial patterns of global temperature and precipitation changes, as well as corresponding large-scale circulation patterns during the latter part of the 9th and 5th millennia BP (4800-4500 versus 4500-4000 BP and 9200-8800 versus 8800-8000 BP) are compared through a group of transient simulations using the Community Climate System Model version 3 (CCSM3). Both periods are characterized by significant sea surface temperature (SST) decreases over the North Atlantic, south of Iceland. Temperatures were also colder across the Northern Hemisphere but warmer in the Southern Hemisphere. Significant precipitation decreases are seen over most of the Northern Hemisphere, especially over Eurasia and the Asian monsoon regions, indicating a weaker summer monsoon. Large precipitation anomalies over northern South America and adjacent ocean regions are related to a southward displacement of the Intertropical Convergence Zone (ITCZ) in that region. Climate changes in the late 9th millennium BP (the "8.2 ka event") are widely considered to have been caused by a large freshwater discharge into the northern Atlantic, which is confirmed in a meltwater forcing sensitivity experiment, but this was not the cause of changes occurring between the early and latter halves of the 5th millennium BP. Model simulations suggest that a combination of factors, led by long-term changes in insolation, drove a steady decline in SSTs across the North Atlantic and a reduction in the North Atlantic Meridional Overturning Circulation (AMOC), over the past 4500 years, with associated teleconnections across the globe, leading to drought in some areas. Multi-century-scale fluctuations in SSTs and AMOC strength were superimposed on this decline. This helps explain the onset of neoglaciation around 5000-4500 BP, followed by a series of neoglacial advances and retreats during recent millennia. The "4.2 ka BP Event" appears to have been one of several late Holocene multi-century fluctuations that were embedded in the long-term, low-frequency change in climate that occurred after similar to 4.8 ka. Whether these multi-century fluctuations were a response to internal centennialscale ocean-atmosphere variability or external forcing (such as explosive volcanic eruptions and associated feedbacks) or a combination of such conditions is not known and requires further study.