Although psychosis is a defining feature of Lewy body disease, psychotic symptoms occur in a subset of patients with every major neurodegenerative disease. Few studies, however, have compared disease-related rates of psychosis prevalence in a large autopsy-based cohort, and it remains unclear how diseases differ with respect to the nature or content of the psychosis. We conducted a retrospective chart review of 372 patients with autopsy-confirmed neurodegenerative pathology: 111 with Alzheimer’s disease, 59 with Lewy body disease and concomitant Alzheimer’s disease, 133 with frontotemporal lobar degeneration (FTLD) with tau inclusions (including progressive supranuclear palsy, corticobasal degeneration or Pick’s disease), and 69 with FTLD and TDP inclusions (FTLD-TDP, including types A–C). Psychosis content was classified by subtype, and the frequency of each subtype was compared among pathological diagnoses using logistic regression. A total of 111 of 372 patients had psychosis. Compared to other groups, patients with Lewy body disease/Alzheimer’s disease pathology were significantly more likely to have hallucinations and were more likely to have more than one subtype of hallucination. Patients with Braak Parkinson stage 5–6 Lewy body disease were significantly more likely than those with no Lewy body disease to have visual hallucinations of misperception, peripheral hallucinations, hallucinations that moved, hallucinations of people/animals/objects, as well as delusions regarding a place and delusions of misidentification. The feeling of a presence occurred significantly more frequently in patients with Lewy body disease/Alzheimer’s disease than all other pathologies. Patients with FTLD-TDP were significantly more likely to have delusions, and for the delusions to occur in the first 3 years of the disease, when compared to patients with Alzheimer’s disease and FTLD-tau, though rates were not significantly greater than patients with Lewy body disease/Alzheimer’s disease. Paranoia occurred more frequently in the FTLD-TDP and Lewy body disease/Alzheimer’s disease categories compared to patients with Alzheimer’s disease or FTLD-tau. Patients with FTLD-TDP pathology had delusions of misidentification as frequently as patients with Lewy body disease/Alzheimer’s disease, and were significantly more likely to have self-elevating delusions such as grandiosity and erotomania compared to patients with other pathologies including FTLD-tau. These data show that the nature and content of psychosis can provide meaningful information about the underlying neurodegenerative pathology, emphasizing the importance of characterizing patients’ psychoses for prediction of the neuropathological diagnosis, regardless of a patient’s clinical syndrome.

Introduction: Today, half of the American homeless population is older than 50 years of age. This shift in age distribution among people experiencing homelessness has challenged our long-held views of the causes of homelessness. Age-related neurological diseases, especially neurodegenerative diseases of the brain (NDDB), may play a role eliciting homelessness in a significant proportion of vulnerable older adults. This article aims to explore relationships between homelessness and NDDB in a cohort of research participants enrolled in observational studies on NDDB at an academic center.Methods: We reviewed charts of the Memory and Aging Center (MAC) of the University of California, San Francisco's database searching for research participants with NDDB that had direct relationship to homelessness. We reviewed all research visits conducted between 2004 and 2018 (N = 5,300). Research participants who had any relationship to homelessness were included in this analysis. NDDB was diagnosed via comprehensive neurological, functional, neuropsychological, and biomarker assessments. Non-parametric tests were used for analysis. Thirteen participants were found to have a direct relationship with homelessness. Seven were female and the median of education was 16 (IR: 12.0–19.5) years. Participants were divided into two groups: Those who experienced homelessness while symptomatic from a NDDB but before formal diagnosis (n = 5, Group 1); and participants with formally diagnosed NDDB who exhibited a new propensity toward homelessness (n = 8, Group 2). Compared to Group 2, participants in Group 1 were younger (p = 0.021) and showed similar results in the neuropsychological evaluation. In both groups, the most prevalent diagnosis was frontotemporal dementia. In Group 1, the majority of participants became homeless in the setting of a fragile socioeconomic situation and informants believed that NDDB contributed or caused their homeless state. In Group 2, a new propensity toward homelessness became manifest in different ways and it stood out that all of these participants were well-supported by family and friends during their illness.Conclusions and Relevance: This case series highlights the role that NDDB may have in precipitating homelessness among vulnerable older adults, particularly in the setting of challenging socioeconomic circumstances and unsupportive living environments. Social ramifications of these findings, particularly pertaining to challenges around rehousing these individuals is discussed.

ImportanceThe neurological substrates of visual artistic creativity (VAC) are unknown. VAC is demonstrated here to occur early in frontotemporal dementia (FTD), and multimodal neuroimaging is used to generate a novel mechanistic hypothesis involving dorsomedial occipital cortex enhancement. These findings may illuminate a novel mechanism underlying human visual creativity.ObjectiveTo determine the anatomical and physiological underpinnings of VAC in FTD.Design, Setting, and ParticipantsThis case-control study analyzed records of 689 patients who met research criteria for an FTD spectrum disorder between 2002 and 2019. Individuals with FTD and emergence of visual artistic creativity (VAC-FTD) were matched to 2 control groups based on demographic and clinical parameters: (1) not visually artistic FTD (NVA-FTD) and (2) healthy controls (HC). Analysis took place between September 2019 to December 2021.Main Outcomes and MeasuresClinical, neuropsychological, genetic, and neuroimaging data were analyzed to characterize VAC-FTD and compare VAC-FTD with control groups.ResultsOf 689 patients with FTD, 17 (2.5%) met VAC-FTD inclusion criteria (mean [SD] age, 65 [9.7] years; 10 [58.8%] female). NVA-FTD (n = 51; mean [SD] age, 64.8 [7] years; 25 [49.0%] female) and HC (n = 51; mean [SD] age, 64.5 [7.2] years; 25 [49%] female) groups were well matched to VAC-FTD demographically. Emergence of VAC occurred around the time of onset of symptoms and was disproportionately seen in patients with temporal lobe predominant degeneration (8 of 17 [47.1%]). Atrophy network mapping identified a dorsomedial occipital region whose activity inversely correlated, in healthy brains, with activity in regions found within the patient-specific atrophy patterns in VAC-FTD (17 of 17) and NVA-FTD (45 of 51 [88.2%]). Structural covariance analysis revealed that the volume of this dorsal occipital region was strongly correlated in VAC-FTD, but not in NVA-FTD or HC, with a volume in the primary motor cortex corresponding to the right-hand representation.Conclusions and RelevanceThis study generated a novel hypothesis about the mechanisms underlying the emergence of VAC in FTD. These findings suggest that early lesion-induced activation of dorsal visual association areas may predispose some patients to the emergence of VAC under certain environmental or genetic conditions. This work sets the stage for further exploration of enhanced capacities arising early in the course of neurodegeneration.

Background and objectivesThe homeless population in the US is aging. Cognitive impairment is prevalent in this population, yet little is known about the neurologic etiologies of such impairment. Addressing this gap in knowledge is important because homeless older adults with cognitive impairment due to neurodegenerative disease may need lifelong tailored support to obtain and maintain housing. In this study, we characterized the neurocognitive health of a sample of adults who experienced homelessness for the first time after age 50 using gold standard behavioral neurology examination practices.MethodsWe conducted a descriptive cross-sectional study of older adults who first experienced homelessness after age 50. We recruited our sample purposively from an ongoing longitudinal cohort study of adults who were aged 50 and over and homeless when they entered the cohort. For this sub study, we enrolled a convenience sample from those who reported their first episode of homelessness after age 50. We did not exclude individuals based on history of substance use. Neurologists conducted a structured neurocognitive history intake, neurological examination, neuropsychological evaluation, and functional assessment between November 2020 and February 2021. We screened all participants for neurocognitive disorders using gold standard clinical research diagnostic criteria.ResultsWe evaluated 25 participants, most were men (76%) and Black (84%), with a median age of 61 years. The most common neurocognitive complaints included deficits in recent episodic memory (n = 15, 60%), executive functions (n = 13, 52%), and behavior/mood, with apathy being the most common complaint (n = 20, 80%). Neuropsychological testing revealed a high prevalence of socioemotional deficits (n = 20, 80%). Common neurological examination deficits included difficulties with coordination, such as impaired Luria task (n = 16, 64%), signs of distal peripheral neuropathy (n = 8, 32%), anosmia/hyposmia (n = 4, 21%), and signs of mild Parkinsonism (n = 5, 20%). The most common diagnoses were MCI (n = 7, 28%), bvFTD (n = 4, 16%), AD (n = 4, 16%), and DLB (n = 2, 8%).DiscussionOur findings suggest that neurocognitive concerns and examination deficits are common among older homeless adults. Specific neurocognitive disorders may be overrepresented in this population, particularly frontotemporal disorders. Longitudinal studies involving brain biomarkers are needed to characterize the neurocognitive health of this vulnerable population more precisely.