Primary Age-Related Tauopathy

Primary age related tauopathy is a neuropathological entity with neurofibrillary tangles confined mainly to the medial temporal lobe (limited to the early to intermediate stages of tangle spread) with little or no amyloid plaque deposition. It is found in older people with normal cognition or mild amnestic impairment.

It is common in the very old at autopsy, and its frequency rises with age from the sixth decade.

Pathophysiology. Hyperphosphorylated tau accumulates in neurons of the entorhinal cortex and hippocampus without amyloid beta plaques, which separates it from Alzheimer disease. Whether it is a separate disease or a prelude to Alzheimer disease is still debated.

Usually mild: slowly progressive amnestic cognitive impairment or normal cognition, with later onset and slower decline than Alzheimer disease. Rarely progresses to severe dementia without another pathology.

Definite diagnosis is by neuropathology. In life, suspect it from an amnestic syndrome in an older person with medial temporal atrophy on MRI, normal CSF amyloid beta 42 or negative amyloid PET and, where available, tau PET uptake limited to the medial temporal lobe. Exclude other causes with MRI, blood tests (thyroid, vitamin B12, glucose, calcium) and mood assessment.

Differential diagnosis.

• Early Alzheimer disease.
• Limbic predominant age related TDP-43 encephalopathy and hippocampal sclerosis.
• Depression, vascular cognitive impairment and medicine effects.

No disease modifying treatment exists. Anti-amyloid antibodies are not indicated in the absence of amyloid. Manage vascular risk factors, hearing, vision, sleep, mood, exercise and cognitive activity, and review drugs affecting cognition. Offer safety advice and support to the person and family.

Monitoring. Annual cognitive testing.