Diencephalic versus Hippocampal Amnesia in Alzheimer's Disease: The Possible Confabulation-Misidentification Phenotype

Abstract

Background: Alzheimer's disease (AD) is clinically heterogeneous, including the classical-amnesic (CA-) phenotype and some variants.

Objective: We aim to describe a further presentation we (re)named confabulation-misidentification (CM-) phenotype.

Methods: We performed a retrospective longitudinal case-series study of 17 AD outpatients with the possible CM-phenotype (CM-ADs). Then, in a cross-sectional study, we compared the CM-ADs to a sample of 30 AD patients with the CA-phenotype (CA-ADs). The primary outcome was the frequency of cognitive and behavioral features. Data were analyzed as differences in percentage by non-parametric Chi Square and mean differences by parametric T-test.

Results: Anterograde amnesia (100%) with early confabulation (88.2%), disorientation (88.2%) and non-infrequently retrograde amnesia (64.7%) associated with reduced insight (88.2%), moderate prefrontal executive impairment (94.1%) and attention deficits (82.3%) dominated the CM-phenotype. Neuropsychiatric features with striking misidentification (52.9%), other less-structured delusions (70.6%), and brief hallucinations (64.7%) were present. Marked behavioral disturbances were present early in some patients and very common at later stages. At the baseline, the CM-ADs showed more confabulation (p < 0.001), temporal disorientation (p < 0.02), misidentification (p = 0.013), other delusions (p = 0.002), and logorrhea (p = 0.004) than the CA-ADs. In addition, more social disinhibition (p = 0.018), reduction of insight (p = 0.029), and hallucination (p = 0.03) persisted at 12 months from baseline. Both the CA- and CM-ADs showed anterior and medial temporal atrophy. Compared to HCs, the CM-ADs showed more right fronto-insular atrophy, while the CA-ADs showed more dorsal parietal, precuneus, and right parietal atrophy.

Conclusion: We described an AD phenotype resembling diencephalic rather than hippocampal amnesia and overlapping the past-century description of presbyophrenia.

Keywords: Alzheimer’s disease; amnesia; confabulation; delusions; memory rehabilitation; misidentification; presbyophrenia.

Fig. 1

Flow-chart of the study sample. We first identified 18 outpatients presenting with a possible confabulation-misidentification phenotype (CM-phenotype) among the patients with AD diagnosis supported by positive biomarkers in the CSF visited in a ten-year period at the Geriatric Unit of the Ca’ Granda Foundation hospital. Then, we excluded one CM-AD patient from this group because she was at moderate stage of dementia (CDR: 2) when she came to our first observation. At the same time, we first selected 33 outpatients presenting with a classical amnesic phenotype (CA-phenotype) among the 36 outpatients with AD diagnosis supported by positive biomarkers in CSF remaining in the outpatient registry in the same period after the extraction of the 18 CM-AD patients. Instead, 3 patients were excluded because presenting an atypical phenotype of AD (i.e., corticobasal syndrome, PCA syndrome, logopenic aphasia). Then, we excluded 3 CA-ADs because they were at advanced stage of dementia (all CDR: 2) at the time of the first visit. In total, 17 CM-ADs and 30 CA-ADs, all at early dementia stage (CDR 0.5 or 1), participated in the cross-sectional study at the time of the baseline assessment. Instead, 17 CM-ADs and 29 CA-ADs participated in the longitudinal study, due to the fact that one CA-AD patient underwent follow-up visits into a different hospital. Finally, we selected 40 people taken from the general outpatient registry in the same Unit among those patients resulted cognitively unimpaired after the neuropsychological assessment, who served as healthy controls (HC) group in the first baseline assessment.

Fig. 2

Frequency of cognitive features detected by clinical assessment (informant report and/or NPE) in the CM-AD group of patients compared to those in the CA-AD and HC group. *indicates a statistically significant difference CM > CA at p < 0.05. **indicates a statistically significant difference CM > CA at p < 0.01. ***indicates a statistically significant difference CM > CA at p < 0.001. (*) indicates a difference CM > CA with tendency to significance.

Fig. 3

Frequency of behavioral features detected by clinical assessment (informant report and/or NPE) in the CM-AD group of patients compared to those in the CA-AD and HC group. *indicates a statistically significant difference CM > CA at p < 0.05. **indicates a statistically significant difference CM > CA at p < 0.01. (*) indicates a difference CM > CA with tendency to significance.