I'm no expert, but for as far as I know registry cleaners just tidy up the "loose ends".
So links to missing items will get removed.
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I use the registry cleaner built into "CCleaner" by Piriform (free). But what currently I have know is some are useful for cleaning up a really messy system to extend the life of an install a few months but many just do heaps of damage, you are better doing prevention rather than cure from piles of installed crapola, Try using Altiris SVS which is a virtual installing environment for installing programs you only want once or will rarely use to avoid it hooking into your real registry. and it's free for personal use.
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Registry Easy