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The causes were several, but the fatal blow came from the Crusaders in 1204. Byzantine was well established and positioned state, but in 11th century the Catholic Europe and Islam changed the balance of power in the region. In year 1000, Byzantine was still the wealthiest kingdom in the world. It prospered as the central crossroad from Europe, Africa, Levant, Middle and Far East and Central Asia. But this wealth was starting bypass Constantinople and landed in emerging Italian city states. In the 11 century, Byzantine engaged on prolonged war with Bulgaria, which were real pain to Byzantine, and they were determine to get rid of them for once. This war was costly, but they achieved total victory in 1018, while performed large scale genocide of the defeated Bulgarians. Byzantine for the first time in 500 years achieved Danube boundary and country was overextended.
Yet at the same century, Turks migrated into central Anatolia and carved much of the state into Sultanate of Rum. Byzantine was unable to stop this threat, since it was exhausted with Bulgarian war, and plus got on the bad term with Pope in 1054. Schism between Constantinople and rest of the Catholic Europe excluded any outside help. Byzantine suffered several defeats, especially in 1071, when their king was captured. Seljuk Turks stayed permanently in Anatolia and were often with 55 miles of Constantinople. From the First Crusades, when Byzantine asked the West for a help against its Islamic neighbors, Byzantine was loosing control of the region. Crusaders decided to take the matter to its own hand and took over Constantinople in 1204. The siege and capture of the city and establishment of the puppet government weakened every aspect of the Byzantine Empire and it had never recovered from this event. The capital ended to play a key economical role in Europe and the Byzantine territory shrunk to a land the size of Switzerland by 1400.
There are several interesting points were the decline of the Byzantine Empire could be detected, but it is usually 1071 The Battle of Manzikert, and siege and fall of Constantinople at 1204.