Local sleep-like cortical reactivity in the awake brain after focal injury.

The functional consequences of focal brain injury are thought to be contingent on neuronal alterations extending beyond the area of structural damage. This phenomenon, also known as diaschisis, has clinical and metabolic correlates but lacks a clear electrophysiological counterpart, except for the long-standing evidence of a relative EEG slowing over the injured hemisphere. Here, we aim at testing whether this EEG slowing is linked to the pathological intrusion of sleep-like cortical dynamics within an awake brain. We used a combination of transcranial magnetic stimulation and electroencephalography (TMS/EEG) to study cortical reactivity in a cohort of 30 conscious awake patients with chronic focal and multifocal brain injuries of ischaemic, haemorrhagic and traumatic aetiology. We found that different patterns of cortical reactivity typically associated with different brain states (coma, sleep, wakefulness) can coexist within the same brain. Specifically, we detected the occurrence of prominent sleep-like TMS-evoked slow waves and off-periods-reflecting transient suppressions of neuronal activity-in the area surrounding focal cortical injuries. These perilesional sleep-like responses were associated with a local disruption of signal complexity whereas complex responses typical of the awake brain were present when stimulating the contralesional hemisphere. These results shed light on the electrophysiological properties of the tissue surrounding focal brain injuries in humans. Perilesional sleep-like off-periods can disrupt network activity but are potentially reversible, thus representing a principled read-out for the neurophysiological assessment of stroke patients, as well as an interesting target for rehabilitation.

Incidence of dementia in the oldest-old and its relationship with age: The Monzino 80-plus population-based study.

INTRODUCTION: Relationship between age and dementia at extreme old ages is still an open question, yet population-based studies in this high-risk age segment are rare. METHODS: The Monzino 80-plus is a population-based study among residents 80 years and older in the Varese province, Italy. Of 1371 eligible individuals, 1294 (94.4%), of whom 64 are centenarians, were included in the incidence study. RESULTS: Since 2002, 584 new cases of all-cause dementia were identified over 15 years. The overall incidence rate was 7.9 per 100 person-years. Dementia risk rose with age (IRR: 1.06), with the cubic model providing the best fit (R2  = 0.91-0.96). Cumulative incidences of dementia unadjusted and adjusted for competing mortality risk progressively diverged with age. CONCLUSION: Dementia incidence also keeps rising in nonagenarians and centenarians. Slowing down in growing risk of developing dementia with age is mainly attributable to increasing competing risk of death and resulting selective survival of individuals at lower risk of dementia.

Stratification of unresponsive patients by an independently validated index of brain complexity.

OBJECTIVE: Validating objective, brain-based indices of consciousness in behaviorally unresponsive patients represents a challenge due to the impossibility of obtaining independent evidence through subjective reports. Here we address this problem by first validating a promising metric of consciousness-the Perturbational Complexity Index (PCI)-in a benchmark population who could confirm the presence or absence of consciousness through subjective reports, and then applying the same index to patients with disorders of consciousness (DOCs). METHODS: The benchmark population encompassed 150 healthy controls and communicative brain-injured subjects in various states of conscious wakefulness, disconnected consciousness, and unconsciousness. Receiver operating characteristic curve analysis was performed to define an optimal cutoff for discriminating between the conscious and unconscious conditions. This cutoff was then applied to a cohort of noncommunicative DOC patients (38 in a minimally conscious state [MCS] and 43 in a vegetative state [VS]). RESULTS: We found an empirical cutoff that discriminated with 100% sensitivity and specificity between the conscious and the unconscious conditions in the benchmark population. This cutoff resulted in a sensitivity of 94.7% in detecting MCS and allowed the identification of a number of unresponsive VS patients (9 of 43) with high values of PCI, overlapping with the distribution of the benchmark conscious condition. INTERPRETATION: Given its high sensitivity and specificity in the benchmark and MCS population, PCI offers a reliable, independently validated stratification of unresponsive patients that has important physiopathological and therapeutic implications. In particular, the high-PCI subgroup of VS patients may retain a capacity for consciousness that is not expressed in behavior. Ann Neurol 2016;80:718-729.

Prevalence of dementia in the oldest old: the Monzino 80-plus population based study.

BACKGROUND: Epidemiological studies commonly include too few of the oldest old to provide accurate prevalence rates of dementia in older age groups. Estimates of the number of those affected, necessary for healthcare planning, are thus flawed. The objective is to estimate the prevalence of dementia and levels of dementia severity in a very large population of oldest old and to investigate the relation between age and dementia prevalence in the extreme ages. METHODS: The Monzino 80-plus is a population-based study among residents 80 years or older in Varese province, Italy. Dementia cases were identified using a one-phase design. The survey was conducted in the participant's place of residence, whether home or institution. Both participants and informants were interviewed. Information was available for 2504 of the 2813 residents (89%). RESULTS: In all, 894 individuals (714 women and 180 men) met the Diagnostic and Statistical Manual of Mental Disorders (fourth edition) criteria for dementia, for a standardized prevalence of 25.3% (95% confidence interval [CI]: 23.4, 27.2%), 28.5% (95% CI: 26.2, 30.9) in women and 18.6% (95% CI: 15.2, 21.9) in men. Age-specific prevalence estimates of dementia increased with age from 15.7% at age 80 to 84 years to 65.9% at age 100 years and higher. For women, prevalence continued to rise after age 100 years, from 64.8% at age 100 to 101 years to 76.1% at age 102 to 107 years. After age 85 years prevalence rates tended to rise linearly, on average 2.6% per year in women and 1.8% in men. About 80% of the cases were moderate or severe. The frequency of mild dementia decreased and that of severe dementia increased with age. CONCLUSION: One-quarter of 80-plus year olds are affected by dementia, mostly moderate or severe. Prevalence rates of dementia do not level off, but continue to rise gradually even in the extreme ages.