Title : Alzheimer’s Disease (AD) with preexisting hypofrontality versus frontal AD: radiologic and neuropsychological data in a case of likely dysexecutive alzheimer’s disease in a patient with schizophrenia
Abstract:
Frontal Alzheimer’s disease (fAD) is an atypical AD variant which is difficult to differentiate from and frequently misdiagnosed as behavioural variant frontotemporal dementia (bvFTD). Most recent work has identified two subtypes of fAD: a behavioural subtype (bAD) associated with changes in personality, behaviour, which may include impulsivity, agitation, aggression, apathy and social cognition, and a dysexecutive subtype (dAD) associated with issues in planning, problem-solving, and other aspects of executive functioning. bAD and dAD are poorly understood in terms of cognitive and behavioural clinical presentations, as well as in a “typical” radiographic pattern of atrophy and hypometabolism beyond predominantly frontal and anterior temporal lobe involvement. This report describes a case of a 61-yearold male patient with a several-decade history schizophrenia, a primary psychiatric condition associated with structural and functional frontal lobe abnormalities, who presented with insidious onset and gradual worsening over the most recent 6-7 months of short-term memory difficulties, apathy, disinterest and anhedonia, with no reported mood changes. Family collateral report indicated significant decline in instrumental activities of daily living (particularly those requiring planning), and recent difficulties in language comprehension. FDG-PET and MRI scans indicated elements consistent with FTLD (frontal and temporal hypometabolism involving superior medial frontal and inferior frontal gyri, anterior cingulate gyrus, Heschl’s gyrus, and caudate nucleus), typical AD (posterior cingulate and precuneus hypometabolism, pronounced bilateral mesial temporal lobe atrophy), mild white matter disease (T2-FLAIR
subcortical/periventricular hyperintensities), and there was additional suggestion that findings may reflect long-term effects of schizophrenia and/or chronic antipsychotic use. Neuropsychological evaluation revealed significant dysexecutive features in working memory, strategy formation, behavioural inhibition, visuoconstructional planning, and verbal generativity, as well as poor confrontation naming and slowed encoding and variable storage and retrieval deficits for nonverbal and verbal non-contextual and contextual information. Deficits were not consistent with an FTLD-related primary progressive aphasia (PPA) or bvFTD alone, nor were they strongly consistent with typical or early onset AD, schizophrenia, or vascularly-derived neurocognitive disorder given the range and severity of deficits observed; while presentation and reported history was not consistent with bAD or bvFTD or any PPA subtype. From these data, a likely dAD diagnosis is offered, which adds to our current, limited understanding of the condition. Additional radiographic workup such as amyloid or tau-PET may be beneficial to confirm diagnosis and elucidate patterns of structural abnormality and/or hypometabolism to improve diagnostic speed and clarity in the dAD and bAD phenotypes of fAD.
