Diagnosis
Alzheimers disease can only be definitively diagnosed with autopsy findings; in the absence of autopsy, clinical diagnoses of AD are "possible" or "probable", based on other findings. Up to 23% of those clinically diagnosed with AD may be misdiagnosed and may have pathology suggestive of another condition with symptoms that mimic those of AD.AD is usually clinically diagnosed based on the persons medical history, history from relatives, and behavioral observations. The presence of characteristic neurological and neuropsychological features and the absence of alternative conditions supports the diagnosis. Advanced medical imaging with computed tomography (CT) or magnetic resonance imaging (MRI), and with single-photon emission computed tomography (SPECT) or positron emission tomography (PET), can be used to help exclude other cerebral pathology or subtypes of dementia. Moreover, it may predict conversion from prodromal stages (mild cognitive impairment) to Alzheimers disease. FDA-approved radiopharmaceutical diagnostic agents used in PET for Alzheimers disease are florbetapir (2012), flutemetamol (2013), florbetaben (2014), and flortaucipir (2020). Because many insurance companies in the United States do not cover this procedure, its use in clinical practice is largely limited to clinical trials as of 2018.Assessment of intellectual functioning including memory testing can further characterise the state of the disease. Medical organizations have created diagnostic criteria to ease and standardise the diagnostic process for practising physicians. Definitive diagnosis can only be confirmed with post-mortem evaluations when brain material is available and can be examined histologically for senile plaques and neurofibrillary tangles.
Likewise the hypothesis is, that as infants go through states of cognitive development, people with Alzheimers disease go through the reverse process of progressive cognitive impairment.The association with celiac disease is unclear, with a 2019 study finding no increase in dementia overall in those with CD, while a 2018 review found an association with several types of dementia including Alzheimers disease. Pathophysiology
Neuropathology
Alzheimers disease is characterised by loss of neurons and synapses in the cerebral cortex and certain subcortical regions. This loss results in gross atrophy of the affected regions, including degeneration in the temporal lobe and parietal lobe, and parts of the frontal cortex and cingulate gyrus. Degeneration is also present in brainstem nuclei particularly the locus coeruleus in the pons. Studies using MRI and PET have documented reductions in the size of specific brain regions in people with Alzheimers disease as they progressed from mild cognitive impairment to Alzheimers disease, and in comparison with similar images from healthy older adults.Both Aβ plaques and neurofibrillary tangles are clearly visible by microscopy in brains of those with Alzheimers disease, especially in the hippocampus. However, Alzheimers disease may occur without neurofibrillary tangles in the neocortex. Plaques are dense, mostly insoluble deposits of beta-amyloid peptide and cellular material outside and around neurons. Tangles (neurofibrillary tangles) are aggregates of the microtubule-associated protein tau which has become hyperphosphorylated and accumulate inside the cells themselves.